BRUCE ROSEMAN, M.D.
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BRUCE ROSEMAN, M.D.
NICOLE LIVESCU, R.N.
Pneumonia Vaccine May Protect Your Heart,
There's substantial (but controversial) evidence that the PPSV shot (pneumococcal polysaccharide vaccine) may dampen the fire of inflammation and keep artery-blocking plaque from rupturing and causing a heart attack or stroke - especially if you're at risk of heart disease. In fact, the rate of myocardial infarction (ER talk for heart attack) was 50 percent lower in people who had gotten the shot two years earlier than recommended, according to a recent Canadian hospital study.
There are a couple of theories about why a vaccine that neuters nasty pneumonia bugs also protects your heart. One is that it specifically inhibits the kind of inflammation that riles up cardiovascular disease. Another is that the antibodies it generates handcuff lousy LDL cholesterol in a way that keeps the cholesterol from building plaque in your arteries.
But frankly, we're not waiting for the definitive explanation to get the shot (Oz just turned 50, so he's due). Not getting pneumonia or heart disease is more than reason enough for us - and you - to get vaccinated. If you need another prod, consider this: About one-third of deaths blamed on H1N1 (aka swine flu), which is still lurking out there, have been in people who've also had bacterial pneumonia.
The You Docs - Mike Roizen and Mehmet Oz - are authors of the best-selling "You: On A Diet." To submit questions and for more info, go to www.RealAge.com.
special note from Dr. Roseman:  Yes, I am aware of the recent Kaiser Study saying it does not help. Nevertheless, it has no downside, I am taking it myself and I am reccomending it to others.

The Risks of Aspirin
The Lancet, Volume 373, Issue 9678, Pages 1849 - 1860, 30 May 2009
Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials

Low-dose aspirin is of definite and substantial net benefit for many people who already have occlusive vascular disease. We have assessed the benefits and risks in primary prevention.
Methods
We undertook meta-analyses of serious vascular events (myocardial infarction, stroke, or vascular death) and major bleeds in six primary prevention trials (95 000 individuals at low average risk, 660 000 person-years, 3554 serious vascular events) and 16 secondary prevention trials (17 000 individuals at high average risk, 43 000 person-years, 3306 serious vascular events) that compared long-term aspirin versus control. We report intention-to-treat analyses of first events during the scheduled treatment period.
Findings
In the primary prevention trials, aspirin allocation yielded a 12% proportional reduction in serious vascular events (0·51% aspirin vs 0·57% control per year, p=0·0001), due mainly to a reduction of about a fifth in non-fatal myocardial infarction (0·18% vs 0·23% per year, p<0·0001). The net effect on stroke was not significant (0·20% vs 0·21% per year, p=0·4: haemorrhagic stroke 0·04% vs 0·03%, p=0·05; other stroke 0·16% vs 0·18% per year, p=0·08). Vascular mortality did not differ significantly (0·19% vs 0·19% per year, p=0·7). Aspirin allocation increased major gastrointestinal and extracranial bleeds (0·10% vs 0·07% per year, p<0·0001), and the main risk factors for coronary disease were also risk factors for bleeding. In the secondary prevention trials, aspirin allocation yielded a greater absolute reduction in serious vascular events (6·7% vs 8·2% per year, p<0.0001), with a non-significant increase in haemorrhagic stroke but reductions of about a fifth in total stroke (2·08% vs 2·54% per year, p=0·002) and in coronary events (4·3% vs 5·3% per year, p<0·0001). In both primary and secondary prevention trials, the proportional reductions in the aggregate of all serious vascular events seemed similar for men and women.
Interpretation
In primary prevention without previous disease, aspirin is of uncertain net value as the reduction in occlusive events needs to be weighed against any increase in major bleeds. Further trials are in progress.


Tomato pill beats heart disease
Scientists say a natural supplement made from tomatoes, taken daily, can stave off heart disease and strokes.
The tomato pill contains an active ingredient from the Mediterranean diet - lycopene - that blocks "bad" LDL cholesterol that can clog the arteries.
Ateronon, made by a biotechnology spin-out company of Cambridge University, is being launched as a dietary supplement and will be sold on the high street.
Experts said more trials were needed to see how effective the treatment is.
Preliminary trials involving around 150 people with heart disease indicate that Ateronon can reduce the oxidation of harmful fats in the blood to almost zero within eight weeks, a meeting of the British Cardiovascular Society will be told at Ateronon's launch on Monday.
“ Our advice to heart disease patients or those at high risk is to rely on proven medications prescribed by their doctor, and aim to get the benefits of a Mediterranean diet by eating plenty of fresh fruit and veg ”
Professor Peter Weissberg of the British Heart Foundation
Neuroscientist Peter Kirkpatrick, who will lead a further research project at Addenbrooke's Hospital in Cambridge on behalf of Cambridge Theranostics Ltd, said the supplement could be much more effective than statin drugs that are currently used by doctors to treat high cholesterol.
But Professor Peter Weissberg of the British Heart Foundation said: "As always, we caution people to wait for any new drug or modified 'natural' product to be clinically proven to offer benefits before taking it.
"It will take some time, and several clinical trials, to provide such evidence for Ateronon.
"In the meantime, our advice to heart disease patients or those at high risk is to rely on proven medications prescribed by their doctor, and aim to get the benefits of a Mediterranean diet by eating plenty of fresh fruit and veg."
He said the British Heart Foundation had supported some of the basic science at Cambridge University underpinning the development of the product.
Professor Anthony Leeds, trustee of the cholesterol charity Heart UK, said: "The new lycopene product Ateronon represents an entirely new approach to the treatment of high blood cholesterol and opens up the exciting possibility."
He said the preliminary findings were "very promising".
Lycopene is an antioxidant contained in the skin of tomatoes which gives them their red colour. But lycopene ingested in its natural form is poorly absorbed.
Ateronon contains a refined, more readily absorbed version of lycopene that was originally developed by Nestle.
Dr Peter Coleman of The Stroke Association said: "We know that diets rich in antioxidants are beneficial in reducing the plaque build up and welcome the findings of this research."
Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/2/hi/health/8076556.stm

Published: 2009/06/01 08:58:18 GMT

Aspirin: More Evidence That Low Dose is All That is Needed
from Heartwire — a professional news service of WebMD
March 19, 2009 (New York, New York) — New guidance on how aspirin should be used in both the primary and secondary prevention of coronary heart disease has come from three new reports published this week.
Two new studies deal with aspirin use in secondary prevention. These are a post hoc analysis of aspirin use in the CHARISMA trial [1] and results of the effect of aspirin use in the Women's Health Initiative (WHI) [2]. Both of these studies found that low-dose aspirin is just as effective as a full dose for secondary prevention.
The third paper outlines new recommendations from the US Preventive Services Task Force (USPSTF) on the use of aspirin for the primary prevention of coronary heart disease [3]. These encourage men aged between 45 and 79 years and women aged between 55 and 79 years to use aspirin when the potential benefit of a reduction in MI for men or stroke for women outweighs the potential harm of an increase in gastrointestinal hemorrhage. They say there are insufficient data to assess the balance of benefits and harms of aspirin for cardiovascular disease prevention in men and women 80 years or older and that aspirin use should not be encouraged for cardiovascular disease prevention in women younger than 55 years and in men younger than 45 years.
CHARISMA: Low-Dose Aspirin for Secondary Prevention
The CHARISMA study, published in the March 17, 2009 issue of the Annals of Internal Medicine, was a randomized trial of long-term clopidogrel vs placebo in patients with atherosclerotic disease or multiple risk factors for heart disease. Aspirin was given to all patients in the trial at a dose of 75 to 162 mg/day, but the actual dose was determined individually by each patient's doctor. The current paper is a post hoc observational analysis of the effect of aspirin by dose. Daily aspirin doses were categorized as <100 mg (n= 7180), 100 mg (n=4961), and >100 mg (n=3454).
Results showed no overall differences in efficacy or safety by aspirin dose. However, in the subgroup of patients randomly assigned to clopidogrel, there was a hint of reduced efficacy and increased harm with higher doses. The researchers conclude: "Lower aspirin doses (75 to 81 mg/day) may optimize efficacy and safety for patients requiring aspirin for long-term prevention, especially those taking clopidogrel."
More Reliable Data to Come From OASIS-7
In an accompanying editorial [4], Dr Shamir Mehta (McMaster University, Hamilton, ON) notes that these results extend earlier observations made in the CURE trial, with CHARISMA having a much longer follow-up and thus allowing a more realistic evaluation of the efficacy and safety of different aspirin doses for cardiovascular disease prevention.
But he points out that these results are still based on post hoc, nonrandomized comparisons and are thus subject to bias and that more reliable information on the question of aspirin dose should come from the ongoing CURRENT-OASIS-7 trial, which is the first large-scale randomized trial to directly compare aspirin doses. This trial is a 2x2 factorial study in 25 000 patients, with the first randomization to high-dose vs standard-dose clopidogrel and the second randomization to daily high-dose vs low-dose aspirin. Results are expected later this year.
WHI: Better Data on Women
The WHI study, published in the March 2009 issue of Circulation: Cardiovascular Quality and Outcomes, provides additional evidence that aspirin may reduce the risk of death in postmenopausal women who have heart disease or who have had a stroke and, in concurrence with the CHARISMA data, show that low-dose aspirin is just as effective as higher doses.
In an interview with heartwire, Dr Jacques Rossouw (chief of the WHI branch at the National Heart, Lung, and Blood Institute, Bethesda, MD), said that current recommendations for women to take aspirin for the secondary prevention of heart disease are based on clinical trials in which women have not been well represented. "Our study is wider than previous studies, in that it included women with any form of cardiovascular disease and women older than have been studied before. We found that total mortality and cardiovascular mortality were lowered in aspirin users and that the benefit does not seem to be dose-related, whereas the side effects are dose-related. So a low dose (75 mg) seems better overall than a full dose (325 mg). And if you can reduce risk with an intervention as simple as a low-dose aspirin every day, then that's quite something."
The WHI Observational Study followed 93 676 postmenopausal women between the ages of 50 and 79 for an average of eight years. Among 8928 women with stable cardiovascular disease, 4101 (46%) reported taking aspirin, of whom 30% were on 81 mg and 70% were on 325 mg. At 6.5 years of follow-up, no significant association was noted for aspirin use and all-cause mortality or cardiovascular events. However, after multivariate adjustment, regular aspirin users had a 25% lower risk of death from cardiovascular disease and a 14% lower risk of death from any cause. Aspirin use was associated with a trend toward lower risk of cardiovascular events, which did not meet statistical significance. Compared with 325 mg, use of 81 mg was not significantly different for all-cause mortality, cardiovascular events, or any individual end point.
Adjusted Hazard Ratio for Death or Cardiovascular Events in Aspirin Users vs Aspirin Nonusers
Outcome   
The researchers note that the 46% figure for aspirin use is low and that this underutilization was most pronounced in blacks and women with Medicaid insurance.
New Primary-Prevention Recommendations
The new USPSTF recommendations on the use of aspirin for primary prevention of heart disease are also published in the March 17, 2009, issue of the Annals of Internal Medicine.
They also favor low-dose aspirin, pointing out that a dose of 75 mg/day seems as effective as higher dosages, but that the risk of gastrointestinal bleeding may increase with dose.
In his editorial, Mehta notes that these guidelines were last published in 2002 and were based on trials with limited data on women, whereas the new recommendations incorporate the results of the landmark Women's Health Study (WHS), which showed no reduction in MI and death with aspirin but a significant reduction in stroke. The new recommendations thus advise use of aspirin in men to reduce MI and in women to reduce stroke.
Mehta points out that a valuable feature of the new USPSTF recommendations is the emphasis on shared decision making: discussing the benefits and risks of initiating aspirin and individualizing decision making to the specific patient or situation. But he adds that there is one group of patients who should absolutely avoid aspirin--those who are at relatively high risk for intracranial bleeding.
He concludes: "The USPSTF has provided us with an important document that is clear and user-friendly for the busy clinician. Aspirin continues to be underused, and the routine incorporation of the USPSTF's recommendations into the daily practice of clinicians will no doubt increase the use of aspirin and, in turn, prevent many thousands of cardiovascular events every year."
Steinhubl SR, Bhatt DL, Brennan DM, et al. Aspirin to prevent cardiovascular disease: the association of aspirin dose and clopidogrel with thrombosis and bleeding. Ann Intern Med 2009; 150:379-386. Abstract
Berger JS, Brown DL, Burke GL. Aspirin use, dose, and clinical outcomes in postmenopausal women with stable cardiovascular disease--the Women's Health Initiative Observational Study. Circ Cardiovasc Qual Outcomes 2009; 2:78-87.
US Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: US Preventive Services Task Force recommendation statement. Ann Intern Med 2009; 150:396-404. Abstract
Mehta SR. Aspirin for prevention and treatment of cardiovascular disease. Ann Intern Med 2009; 150:414-416. Abstract
The complete contents of Heartwire, a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.

once a week crestor for people who are unable to take it otherwise
Source: Am J Cardiol | Posted 1 week ago
Once-a-week rosuvastatin (2.5 to 20 mg) in patients with a previous statin intolerance; Ruisinger JF, Backes JM, Gibson CA, Moriarty PM; American Journal of Cardiology 103 (3), 393-4 (Feb 2009)

The purpose of this study was to determine the efficacy of rosuvastatin dosed once a week in patients with a previous statin adverse event. Rosuvastatin once a week was tolerated by 37 (74%) of the 50 study participants, with doses ranging from 2.5 mg to 20 mg a week (mean 10 +/- 4 mg). Patients tolerating the once-a-week regimen experienced a 17% reduction in total cholesterol, 23% reduction in low-density lipoprotein cholesterol, 12% reduction in triglycerides, and a 5% increase in high-density lipoprotein cholesterol (all p<0.001), during a mean follow-up of 4 months +/- 2. Although this alternative dosing regimen has not been proven to reduce cardiovascular events, it may provide a therapeutic option for patients who may otherwise go without the proven benefits of statin therapy. In conclusion, this dosing strategy was well tolerated in patients with a history of an adverse event to 1 or more statins and led to significant lipoprotein changes.

Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.
N Engl J Med. 2008; 359(21):2195-207 (ISSN: 1533-4406) Ridker PM ; Danielson E ; Fonseca FA ; Genest J ; Gotto AM ; Kastelein JJ ; Koenig W ; Libby P ; Lorenzatti AJ ; MacFadyen JG ; Nordestgaard BG ; Shepherd J ; Willerson JT ; Glynn RJ ;
Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA. pridker@partners.org
BACKGROUND: Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment. METHODS: We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. RESULTS: The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P=0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P=0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P=0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes. CONCLUSIONS: In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events. (ClinicalTrials.gov number, NCT00239681.)


Lipitor Cuts Artery Clogs After Heart Attack
NEW YORK (Reuters Health) - Early treatment with Lipitor (news - web sites) (atorvastatin), a "statin" cholesterol-lowering drug, reduces the build-up of artery-clogging plaque in patients who've had a recent heart attack, new research suggests.

"This is the first evidence that plaque can regress with early statin treatment in heart attack patients," lead author Dr. Shinya Okazaki, from Juntendo University School of Medicine in Tokyo, said in a statement. "This evidence provides further support for the use of statins after a heart attack."

The study involved 70 patients who experienced a heart attack or related problem and were treated with atorvastatin or instructed to eat a cholesterol-lowering diet. The findings are reported in the American Heart Association (news - web sites)'s journal Circulation.

During the 6-month study, levels of LDL ("bad") cholesterol decreased by 42 percent in the Lipitor group, but rose by 1 percent in the diet group. Similarly, in Lipitor-treated patients, plaque size fell by 13 percent, while in diet-treated patients, the size increased by 9 percent.

Further analysis showed that the drop in plaque size was related to the LDL cholesterol level at follow-up, and with the overall reduction in LDL cholesterol. This was observed even in patients with low LDL cholesterol levels from the start.

"The positive effect of (Lipitor) was evident whether people went into the study with an LDL cholesterol above 125 mg/dL or not, indicating that this...therapy would be beneficial whether people who have heart attacks have very high cholesterol or not," Okazaki noted.

Further studies are needed to determine how Lipitor stabilize plaques and whether the benefits seen with Lipitor apply to other statins, the authors state.
SOURCE: Circulation, August 31, 2004.

"Fitness Cuts Men's Heart Disease Risk in Half: New Queen's Study"
KINGSTON, ON -- September 2, 2005 -- Being physically fit can dramatically reduce men's deaths from heart disease -- even when their cholesterol rates are high, says Queen's researcher Peter Katzmarzyk. His new study to be published Tues. Sept. 6 by Circulation: Journal of the American Heart Association shows that, regardless of their cholesterol level, men can cut by half their risk of dying from cardiovascular disease if they are physically fit. Other Queen's members of the team, from the School of Physical and Health Education, are Chris Ardern and Ian Janssen. Researchers Timothy Church and Steven Blair from the Cooper Institute Centres for Integrated Health Research in Dallas, Texas, are also on the team. The primary aim of the study was to analyze the effectiveness of last year's modifications to the guidelines from the U.S. National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) for lowering bad (LDL) cholesterol to predict death from cardiovascular diseases. "We wanted to find out if the new guidelines could identify men at risk for cardiovascular disease," says Dr. Katzmarzyk. "We confirmed that the guidelines do accurately identify men at risk not only of disease, but also at risk of cardiovascular death. We also discovered that fitness is important across the board – at every level of cholesterol." Results also suggest that within a given risk category, physical fitness is associated with a greater than 50-per-cent lower risk of mortality. In this study, physical fitness was four to five, 30-minute segments of activity per week: equivalent to walking 130 to 138 minutes per week. Researchers analyzed the cardiovascular risk factors and cardio-respiratory fitness of 19,125 men ages 20 to 79, who were treated at a preventive medicine clinic from 1979 -1995, prior to the revised treatment guidelines. Using the new ATP III classifications: • 58 per cent of the men would have met the criteria for being "at or below LDL (bad) cholesterol goal"; • 18 per cent would have met the criteria for "therapeutic lifestyle change" – meaning diet, physical activity and weight management could lower LDL; and • 24 per cent would have met the criteria for "drug consideration" for lowering LDL. There were 179 deaths from cardiovascular disease over more than 10 years of follow-up. Overall, compared to men who met the acceptable LDL level under the revised guidelines: • Men who met the criteria for therapeutic lifestyle intervention had twice the risk of cardiovascular disease death; and • Men eligible for aggressive cholesterol-lowering therapy had almost seven-times the risk. "Lowering the threshold for consideration of cholesterol-lowering drug therapy for those at high risk will ultimately save lives and also have important implications for the healthcare system," says Dr. Katzmarzyk. The research was partly funded by the U.S. National Institutes of Health. SOURCE: Queen's University


Asian Americans at Risk of 'Silent' Heart Disease
NEW YORK (Reuters Health) - Asian Americans are disproportionately affected by a painless heart condition that can lead to heart attack, researchers reported this week.

Because Asian Americans have an increased risk of the condition, known as silent myocardial ischemia, they would benefit from a more aggressive approach to early diagnosis and management of heart disease, Dr. Antonio Q. Chan of Stanford University Medical Center in California told Reuters Health

Silent myocardial ischemia is a narrowing of the arteries that restricts blood flow to the heart, but, unlike ordinary myocardial ischemia, does not cause pain or other symptoms. The condition predisposes one to later heart problems, including heart attack.

"Any Asian American who complains of shortness of breath after climbing a flight or two of stairs, gets tired easily, or is over age 45 should be examined for the presence of ischemic heart disease," Chan said in a statement.

This is especially important for people with high blood pressure, diabetes or a family history of heart disease, he added.

In an interview with Reuters Health, Chan said "physicians caring for Asian Americans at risk for silent myocardial ischemia should have an interpreter during clinic visits to improve awareness of their symptoms."

He also believes the federal government should waive the mandated five-year waiting period before immigrants can qualify for federal or state health insurance.

"A lot of the folks that I am seeing don't qualify for Medicare because they have not stayed in the U.S. for a minimum of five years," Chan told Reuters Health. "A lot of these patients are in their late 60s and 70s, so waiting for five years might be too late. By the time they are seen, usually they have full-blown heart disease."

Chan and his colleagues presented the results of their study during the American Heart Association (news - web sites)'s Second Asia Pacific Scientific Forum in Honolulu.

In the study, the researchers reviewed the medical records of 973 patients from a largely Asian-American practice in the San Francisco Bay area, and those of 662 patients from a predominantly Caucasian practice in the Chicago area.

All patients were asked in their native language about symptoms of heart disease and underwent several types of cardiac testing.

Among patients with myocardial ischemia, only 30 percent of Asian Americans experienced chest pain, compared with 83 percent of Caucasian Americans.

However, Asian Americans were more likely than whites to have other symptoms, including shortness of breath after exercise (63 percent, versus 36 percent), fatigue (59 percent, versus 22 percent) and heart palpitations (65 percent, versus 24 percent).
Prevention of Preterm Delivery  
Women with a history of preterm delivery are at high risk for recurrence in subsequent pregnancies, and an effective strategy to reduce this risk has been lacking. In this randomized, placebo-controlled trial, weekly injections of 17 alpha-hydroxyprogesterone caproate reduced the risk of delivery before 37 weeks of gestation by one third among such high-risk women.

Therapy with this agent may substantially reduce the likelihood of preterm delivery and its attendant complications in high-risk women and their infants.

New Drug Cuts Risk of Second Stroke, Heart Attack

WEDNESDAY, Nov. 12 (HealthDayNews) -- The anti-clotting medicine clopidogrel reduces the risk of recurrent heart attack and stroke and is cost-effective.

That's the conclusion of an Emory University study presented Nov. 12 at the American Heart Association (news - web sites)'s annual conference in Orlando, Fla.

"We have three separate investigations showing uniform results in both the short- and long-term use of clopidogrel. Specifically, the use of clopidogrel in addition to aspirin produces a significant risk reduction in recurrent heart attack, stroke or cardiovascular death," Dr. William Weintraub, a researcher at the Emory Center for Outcomes Research, says in a prepared statement.



Ambulatory Blood-Pressure Measurements in Patients with Treated Hypertension
FROM THE  NEW ENGLAND JOURNAL 6/03
In this prospective, multicenter study of treated hypertensive patients, ambulatory blood-pressure readings predicted the risk of cardiovascular events during five years of follow-up, even after adjustment for office-based blood-pressure measurements and other cardiovascular risk factors.

Twenty-four–hour ambulatory blood-pressure monitoring may be used to improve the stratification of treated hypertensive patients according to cardiovascular risk, although the role of these measures in the care of such patients remains uncertain.


MRI Artery Scans Predict Stroke Risk-Studies
Mon Jun 9, 5:30 PM ET  Add Health - Reuters to My Yahoo!
By Ransdell Pierson

NEW YORK (Reuters) - Magnetic resonance imaging can help predict which patients are at risk of strokes from clogged arteries, and thereby alert patients to have surgery or take protective drugs, according to two studies released on Monday.

The studies involving the carotid artery, appearing in Circulation: Journal of the American Heart Association (news - web sites), were the first to use MRI scans to detect bleeding within fatty plaque material that lines and clogs arteries.

Such bleeding indicates the plaque has become "complicated," meaning the surface of the deposit has broken apart and pieces of it could travel to the brain, forming clots that cause stroke.

Strokes often occur when branches of the carotid artery, the main blood vessel supplying blood from the neck to the brain, become clogged and brain cells become starved of blood and oxygen.

MRI scans used in the two studies detected high-risk complicated plaque in the carotid arteries of 60 percent of patients who had shown signs and symptoms that precede stroke -- including "mini-strokes" which cause no major permanent damage but indicate danger of serious future strokes.

By contrast, MRI scans found no complicated plaque in the carotid arteries of a smaller group of people who had no previous signs or symptoms of stroke.

One of the studies involved 63 patients who had surgery to remove obstructions in the carotid artery.

Fatty deposits removed during the surgeries were later analyzed by conventional pathology techniques and showed complicated plaque in 44 patients.

MRI scans taken before surgery successfully predicted complicated plaque in 41 of the patients, an accuracy rate of 93 percent.

"The MRI studies show that plaque is not some benign quiet process in which the arteries gradually harden," said Dr. Alan Moody, who helped write the two Circulation reports.

"In up to 60 percent of cases, active bleeding is going on within the plaque -- making the plaque bigger and further clogging the artery," said Moody, who is chief radiologist at Sunnybrook and Women's College Health Sciences Center in Toronto.

He said all patients with such bleeding are at elevated risk of stroke and that many could benefit from surgery or certain drugs that help keep plaque from breaking up into dangerous pieces. They include statins, a popular class of cholesterol-lowering medicines.

Angiography is currently the "gold standard" for verifying plaque in arteries. But Moody said the procedure, which involves running a catheter between the patient's groin and neck and then filling it with dye, actually causes strokes in 1 percent of patients.

He said other screening procedures -- including ultrasound, computed tomography and positron emission tomography -- can also indicate the presence of plaque but without the convenience and detailed information available from MRI scans.

"In the future, the new gold standard of identification may be a combination of ultrasound and MRI scans," Moody said, adding that other studies suggest combined use of those non-invasive tests may provide the same detailed level of information as angiography.

Moody said angiography procedures currently cost about $1,000, compared with $250 for ultrasound and $400 for MRI scans.

The Circulation articles said MRI scans might also hold promise in detecting elevated risk of heart attack in patients with complicated plaque.


Raising HDL levels may be as important as lowering LDL
Researchers find that changing the focus of lipid-lowering therapy may improve outcomes, but some experts say it is too soon to alter recommendations.
By Victoria Stagg Elliott, AMNews staff. April 28, 2003.

Targeting drug therapy to raise levels of HDL cholesterol alone may be sufficient to reduce the risk of heart disease and improve cardiovascular health, according to several studies presented at the American College of Cardiology meeting held earlier this month in Chicago.
One study, which was presented by researchers at the Heart Institute, Sheba Medical Center in Tel Hashomer, Israel, found that raising HDL cholesterol was associated with improved long-term survival among more than 1,500 patients with coronary disease.
Another from the Uniformed Services University of Health Sciences in Bethesda, Md., randomized nearly 150 patients with stable coronary disease to receive either medications to raise HDL or a placebo. Those on meds increased their HDL as well as decreasing their total cholesterol significantly and had far fewer heart-related mortality or morbidity events.
"There's ample epidemiologic evidence that HDL cholesterol is very predictive of cardiovascular events," said Maj. Richard A. Krasuski, MD, the study's lead author and director of cardiovascular research at Uniformed Services University. "This study suggests that it could be possible that aiming to raise the HDL may be as good or maybe even better than trying to lower the LDL."
Although these studies focused on people who have already had cardiac events, the strategy does have the potential to impact prevention for those who do not yet have heart disease. "If you have a primary prevention group that has a number of cardiovascular risk factors and a low level of HDL cholesterol, I think looking at ways to raise HDL is certainly a viable option, but it's certainly one that needs further study," said Dr. Krasuski.
Low HDLlevels have long been acknowledged as a heart disease risk factor. Last November's guidelines, the most recent, from the National Institutes of Health's National Cholesterol Education Project, "Detection, Evaluation and Treatment of High Blood Cholesterol in Adults," raised the bar by increasing the definition of low HDL to less than 40 mg/dl from less than 35 mg/dl.
Traditional treatment goals have always been to lower the total cholesterol as well as levels of LDL, and the new guidelines did not suggest an HDL goal. "In all persons with low HDL cholesterol, the primary target of therapy is LDL cholesterol," spelled out the guidelines.
But increasingly, experts are recognizing HDL as an independent risk factor that needs to be addressed. "The epidemiology is strong, and the population data are compelling," said Andrew Tonkin, MD, head of cardiovascular disease epidemiology and prevention at Monash University in Melbourne, Australia.
Experts said, though, that more data were needed before clinical practice should be altered. Head-to-head trials pitting drugs that primarily lower LDL against ones that are most effective at raising HDL are needed.
"I'm kind of a [National Cholesterol Education Program] guideline person, and they were the biggest on the LDL," said Paul Thompson, MD, director of preventive cardiology at Hartford Hospital in Hartford, Conn. "We have less outcome data on raising the HDL than we do on lowering the LDL, and we need outcome data."
No escaping lifestyle changes
The conference was not solely focused on the role of various drug therapies. Experts were quick to point out that lifestyle changes can be just as effective or even more so at improving a patient's cardiac risk profile, either by themselves or with medications. Several studies were presented highlighting that drastic lifestyle alterations can improve heart health.
One study from Indiana University School of Medicine in Indianapolis suggested that exercise could increase the number of vessel wall repair cells circulating in the blood. Another from the University of Texas Medical School at Houston suggested that exercise as well as extreme dietary changes accompanied by traditional lipid-lowering medications may offer advantages over medication with only minor lifestyle changes.
In the UT study, more than 400 patients with coronary artery disease were randomized to receive either no intervention; an intervention involving an extremely low-fat diet combined with exercise and medication; or an intervention combining minor lifestyle changes and traditional drug therapies. The group that exercised and ate an extremely low-fat diet had a cardiac event rate of just over 6%. Those who made only minor changes had a rate of around 20%. Those who did nothing had a rate of 30%.
"Pills don't substitute for diet and exercise," said Stefano Sdringola, MD, lead author and assistant professor of cardiology at the University of Texas Medical School, Houston.

ADDITIONAL INFORMATION:
Focus on HDL levels to reduce coronary disease
Objective: Does therapy targeted at raising HDL cholesterol improve outcomes for heart disease patients?
Method: 143 coronary patients already receiving aggressive dietary and exercise interventions were randomized to receive placebo or gemfibrozil, niacin and cholestyramine to raise their HDL cholesterol.
Results: Total cholesterol increased 3% in the placebo group, but went down 16% in the drug group. Nineteen patients in the placebo group experienced heart-related morbidity or mortality, including unstable angina, transient ischemic attack or stroke. Nine of the drug group experienced such events.
Conclusion: A combination of drugs aimed at increasing HDL improves cholesterol profiles and results in significant reduction in cardiovascular events.
Source: American College of Cardiology, 52nd Annual Scientific Sessions, April 2

Weblink
52nd annual scientific sessions program, American College of Cardiology, (http://www.acc03online.acc.org/)
Third report of the National Cholesterol Education Program expert panel, "Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)," National Heart, Lung, and Blood Institute (http://www.nhlbi.nih.gov/guidelines/cholesterol/)



Framingham Heart Study: The beat goes on
A long-running Massachusetts study on heart disease has dramatically changed the way medicine is practiced today, and it promises to continue to break new ground.
By Susan J. Landers, AMNews staff. Feb. 18, 2002.

In 1948 President Harry S. Truman won an upset victory over Thomas Dewey, Mahatma Gandhi was assassinated, the average income was less than $3,000 a year, life expectancy was 63 years and great numbers of people were dying of cardiovascular disease.
Also in that year, the Framingham Heart Study was begun in an attempt to identify factors that contributed to this growing epidemic of heart disease.
Intended as a 20-year study, it's still going strong. After 53 years it is the longest running prospective epidemiologic study of heart disease ever and researchers are now enrolling the grandchildren of the study's original participants.
Its success is legendary among heart specialists, boosting the fame of the town of Framingham, Mass., and even making its participants somewhat celebrities.
There's no doubt that the study's findings have been important. "The Framingham Heart Study provided the foundation for preventive cardiology as we know it today," said Roger Blumenthal, MD, director of preventive cardiology at Johns Hopkins Hospital in Baltimore.
"It was one of the first to alert doctors and the public that there are major risk factors for heart disease that we now take for granted. But 50 years ago there was still a lot of controversy about what caused heart attacks and strokes," said Dr. Blumenthal, who is also a national spokesperson for the American Heart Assn.
"We've had an enormous impact using data from the Framingham Heart Study to identify people who are at risk and then modifying those risk factors," said Teri Manolio, MD, PhD, director of epidemiology and biometry at the National Institutes of Health National Heart Lung and Blood Institute.
"We've seen heart disease death rates come down dramatically and a lot of that is due to this study," she said.
When the study began, people knew very little about heart disease, much less about its causes and virtually nothing about what could be done to prevent it, said its current director, cardiologist Daniel Levy, MD.
But through the vision of its first director, Thomas Dawber, MD, the Framingham Heart Study was the first to apply the discipline of epidemiology to a chronic, noninfectious disease.
Previously, epidemiology had mostly to do with tracking such diseases as tuberculosis, syphilis, malaria and polio, said Philip Wolf, MD, principal investigator in the Framingham study and a professor of neurology at Boston University.
"The idea that you could use the methods of epidemiology to study chronic disease evolved after World War II, and that's when the Framingham study was conceived," Dr. Wolf said.
Risk factors identified
The assumption was that heart disease would develop in some of the subjects during the study's run. It did.
Researchers were provided the opportunity to closely examine the lifestyles of the participants. And from that examination, the term "risk factor" emerged. "This is really the first time the term was used in the history of the world," Dr. Wolf said.
Researchers found that it was possible from an initial examination to determine which people were at the highest risk of developing heart disease: namely, smokers with high blood pressure and high cholesterol levels.
Previously, physicians saw patients who had already had a stroke or heart attack, said Dr. Wolf, and questions about a patient's lifestyle were answered after the fact. With this study, measurements were made before the illness occurred, he said, allowing researchers to make an unbiased assessment and have a whole group with which to compare.
The discovery of risk factors is not the only finding the study revealed. It has produced more than 1,000 scientific papers and has branched out into other areas.
There have been a number of projects related to the study of arthritis and osteoporosis, noted Dr. Levy. Additional projects underway are related to hearing loss and eye diseases as well as dementia, he added.
The project was funded and run exclusively by the NHLBI until 1971 when Boston University became the principal subcontractor for the study, Dr. Levy said.
The researchers worked with a pool of 5,209 men and women between the ages of 30 and 62 recruited from Framingham, a small town about 20 miles west of Boston. This town was chosen from among several others because it had a successful track record with community projects and its near-Boston location provided proximity to a number of prominent medical researchers, Dr. Levy said.
The study has produced more than 1,000 scientific papers.
Framingham was also fairly isolated in 1948, before construction of the nearby Massachusetts Turnpike.
Since its inception, participants have undergone extensive physical examinations and lifestyle interviews every two to four years.
Many of the original participants have returned for biennial exams for 26 years. For any particular exam at least 85% of the participants return, said Dr. Wolf. The youngest participant in the original cohort is now 84, several are older than 100 and some of the exams are carried out in nursing homes or assisted living facilities, Dr. Wolf said.
"But many still come in," he said. "We had about 300 of the original group turn up for an MRI of their brain."
Meanwhile, the study has also grown from this base. For instance, in 1971, the study recruited 5,124 children and their spouses of the original participants for a second study, called the "Offspring Study."
In 1995, researchers began recruiting from Framingham's growing minority community, the result of an influx of immigrants from Brazil, India and Pakistan. With this effort, known as the Omni study, researchers are investigating whether the risk factors associated with heart disease in these minority populations are the same as risk factors found in the other cohorts.
And last year, researchers mailed about 5,200 cards to the third generation of the original participants. The plan is to recruit about 3,500 grandchildren and their spouses.
By late December, 3,000 or so cards had been returned and about 95% said, "Sure, sign me up," Dr. Wolf said.
Loyal participants
The trust that has built between researchers and subjects is what keeps participants returning for follow-up exams, said Dr. Levy. "It's a mutual relationship," he said.
Study participants return for a variety of reasons, he noted. "Some are motivated by altruism, and some found it an opportunity for a free exam."
No one had health insurance in 1948, he remarked, and for some of the participants the prospect of a free exam was probably enough of an enticement.
As results came in, participants began to understand the importance of the study, a fact that reinforced their resolve to continue.
While the original participants may have thought their volunteerism could, some day, help their own children, little did they know that their children and grandchildren would also become participants in the study.
Thomas Berardi is one of the third-generation participants recently recruited for the study. His mother, described by Berardi as "a worrier," urged her son to take advantage of the opportunity. She was concerned that he wasn't attending to his health as he should be, Berardi said.
With a family history of heart disease -- a grandmother died at about age 70 of a sudden heart attack, a grandfather died of heart disease and his father has had some heart problems -- Berardi, at 49, admits that self-interest is partially responsible for his participation.
"By volunteering, I am going to get the checkups that I may have put off," he said.
But he acknowledges a feeling of pride in the role he and his family have played in helping many people lead longer and healthier lives.
Berardi has a cousin who lives in Florida and is also a study participant. His cousin, who receives his checkups during return visits for family reunions, noted that his Florida physician treated him like a celebrity when he revealed his involvement in the Framingham study.
Poised for the future
Crucial to the study's longevity has been its ability to move with the times and adopt the latest in technology.
When research began, blood pressure, electrocardiogram, medical history and physical exams were the tools employed. Those measures are still used today, Dr. Wolf said. "We try to make the same measurements in 2001 that we used in 1951," he said, "so we can look at changes over time."
But technology marches on. Now researchers have added echocardiography, carotid artery ultrasound and densitometry to their measures.
One important sign that researchers are keeping abreast with modern science is their new focus on genetics. They have much material to work with given the study's multigenerational nature.
"The expansion to a third generation opens up the chance to explore important new questions about disease risk, especially those related to genetics," said NHLBI Director Claude Lenfant, MD.
The researchers have been collecting DNA for about 15 years and developing cell lines for about five years, Dr. Levy said. Thousands of genetic tests will be able to be performed on a single tube of blood, he noted. "We're hoping that with this unique family structure in Framingham and the long-term nature of the data collection here, we will be able to contribute in important ways to understanding the genetic basis for common conditions that are involved in heart disease and stroke."
Participation of the third generation of subjects is also expected to further scientists' understanding of the role of genetics in the development and progression of such diseases as stroke, dementia, osteoarthritis, vision and hearing loss, Dr. Wolf said.
"We'll be able to look at all sorts of things, such as the genetic and environmental characteristics of healthy aging," Dr. Levy pointed out. Framingham researchers are working to identify a region of the human genome that appears to contain a gene that protects individuals from developing heart disease. The gene in this region is related to the production of increased amounts of high density lipoprotein, the "good cholesterol."
Researchers are also looking for locations of genes that increase the risk for heart disease and are focusing on a region containing a gene that appears to cause high levels of low density lipoprotein, the "bad cholesterol."
It is doubtful that there will be an end to the diseases studied by the Framingham Heart Study anytime soon. So does that mean the study will go on forever?
There are no guarantees. The study has to sing for its supper every five, six or seven years, and justify why it should continue, Dr. Manolio said. But it has been very successful in doing so, she added, explaining that the NHLBI soon will be announcing another six- or seven-year extension for the study.
"All I can say is that we are here today because of a track record of productivity and not just that we were productive, but the lessons learned from Framingham in many ways changed the way medicine is practiced in the United States," Dr. Levy said.
Back to top.


Study directors brought a variety of expertise
The Framingham Heart Study has had four directors in its more than 50-year life span. Daniel Levy, MD, the current director, is a clinical cardiologist. He is expanding the study to include the third generation of participants and, in doing so, is refocusing research on the family patterns of disease.
But each of those who came before him left important footprints in the direction the study took and the findings that resulted.
Thomas Dawber, MD, the director from 1949 to 1966, was the architect of the initial project. "He made it happen," Dr. Levy said. Dr. Dawber recruited participants and instituted scientific rigor in the field of epidemiology, which was a fledgling field in medicine.
After him came William Kannel, MD, who directed the study from 1966 to 1979. He was an "amazingly productive researcher," according to Dr. Levy, and the first to take the notion of risk factors and develop it fully. Dr. Kannel was probably the key scientist in the history of the study.
From 1979 to 1995, William Castelli, MD, took the helm. Dr. Levy considers him the ambassador. He got out on the lecture circuit and, with an "evangelical-like fervor," stressed the role of cholesterol as a critical risk factor for heart disease before others joined the fight.

Framingham Heart Study (http://www.framingham.com/heart/)



Exercise  lowers levels of C-reactive protein
In a study of nearly 3,000 adults, Harvard researchers found that those who got the most exercise had the lowest levels of C-reactive protein (CRP), a marker of inflammation that has been tied to the risk of artery disease, heart attack and stroke.

In fact, the same researchers recently found in a large study of women that CRP levels were better predictors of heart attack and other cardiovascular problems than levels of "bad" LDL cholesterol were -- although there's no agreement yet on whether people's CRP levels should be routinely checked.

These latest findings "have enormous public health implications," study author Dr. Michelle A. Albert reported at the meeting.

"Physical activity may attenuate inflammation and modify cardiovascular risk without drug therapy," she said.

The study involved 2,833 men and women, 41 percent of whom had a history of coronary artery disease. Participants were divided into four groups based on exercise habits: those who exercised less than once a week; once a week; two or three times a week; or at least four times a week.

According to Albert, the typical CRP level declined with increasing exercise. And the relationship was seen in all subgroups, including smokers, nonsmokers and those with and without heart disease.

"There was a progressive drop in CRP levels with exercise, even after adjusting for smoking, lipid (cholesterol) levels and age," Albert said.

But greater exercise-related drops in CRP were seen in men than in women, she noted.

The reason is unclear, but Albert speculated that women may engage in less intense exercise or may have a lower overall activity level than men.


Heart Disease: A Woman's Biggest Health Threat
When it comes to heart disease, what women don't know can kill them.

For instance, most women don't realize that heart disease is a bigger threat than any other illness they might face. A recent American Heart Association (news - web sites) survey found that a majority of women thought breast cancer (news - web sites) was the leading cause of death.

"One in 28 women will die of breast cancer, whereas almost one in two will die of heart disease," says Dr. Robert Bonow, president of the heart association and chief of cardiology at Northwestern University in Chicago.

"Partly, it's that women are less aware of their risk factors. They are less likely to see heart disease as an illness that will kill them rather than men," Bonow adds.

In 2000, cardiovascular diseases claimed the lives of 505,661 American women. In the same year, 440,175 men died from these diseases, which range from heart attack to atherosclerosis, a buildup of plaque in the arteries.

With those disturbing statistics as a backdrop, February has been designated American Heart Month. And the American Heart Association (AHA) is working to spread the word that preventive measures and early screening of risk factors can help Americans thwart heart disease before it strikes.

"If we're really going to change this epidemic, it's going to take prevention. People need to know their blood pressure and cholesterol, and they need to be treated effectively," Bonow says.

"Also, people need to be more careful about their diet," he adds. "Our younger population is becoming more obese. And fewer schools are providing physical education."

To underscore the heightened risk facing women, consider these statistics: In 1980, 4 percent more American men died of cardiovascular disease than women. But by 1984, that gap had disappeared.

Today, 15 percent more women than men die of heart disease.

"These diseases claim the lives of more than half a million females every year -- about a death a minute. That's more lives than the next seven causes of death combined," states the American Heart Association.

Part of the problem can be traced to a historical lack of attention on women's health issues. While much research has been done on heart disease in men, it's only in the last decade that researchers have focused studies on women, says Dr. Nieca Goldberg, chief of the Women's Heart Program at Lenox Hill Hospital in New York City.

"I remember in medical school, when instructors referred to heart disease, they would show slides of a middle-aged businessman clutching his chest," says Goldberg, who wrote the book, "Women are Not Small Men: Lifesaving strategies for preventing and healing heart disease in women."

Another point for women to consider is that women and men get heart disease at different points in the lives. For men, it generally shows up in their 40s, but for women it usually doesn't appear until after menopause, around 60. And as the population ages, a growing number of women are being diagnosed with heart disease, Goldberg says.

What's more, men survive heart attacks more often than women. This is partly due to medical improvements in fighting heart attacks, but also because men are generally younger when they are stricken, Bonow says.

And the warning signs for heart attack differ between the sexes. Instead of the characteristic chest pain men get, women often have shortness of breath, exhaustion and discomfort in the lower chest, which can be mistaken for stomach illness. As a result, they frequently don't realize they are having a heart attack, Goldberg says.

"They need to be aware that the earlier they get to the hospital, the more likely we can save them," she says.

To prevent heart disease, women and men must address the three largest risk behaviors -- being overweight, lack of physical activity, and smoking.

Exercise and a diet rich in fruits, vegetables, grains and fish are essential. But so is early screening for high cholesterol and blood pressure. The sooner doctors can detect the warning signs of heart disease in a person, the more likely they can prevent it, experts say.

As part of American Heart Month, the AHA is also stressing the value of CPR training, which can save a heart attack victim's life. The group is also pushing an initiative to increase the number of portable defibrillators in public places.

"Heart disease is not just a U.S. issue. It's also an international issue," Bonow says. "You start with public awareness."


Time of Day Affects Drug's Blood Pressure Control
By Keith Mulvihill

NEW YORK (Reuters Health) - Several different classes of drugs can be used to get blood pressure under control, and now a small study suggests that some may be more effective at certain times of the day than others.

"Different classes of drugs act more effectively at different times of the day," Dr. Trefor O. Morgan told Reuters Health. "This differential effect has not previously been clearly shown."

The new findings suggest that prescribing more than one blood pressure medication may provide more effective treatment, according to Morgan, of the University of Melbourne in Australia.

Normally, a person's blood pressure dips and climbs over a 24-hour period. Blood pressure climbs most rapidly in the morning after awakening and typically plateaus during the middle-to-late portion of the day. It then declines in the evening and is lowest during sleep.

In the current investigation, Morgan and co-author Adrianne Anderson looked at the effects of four different blood pressure medications on 24 people over age 65 with elevated systolic blood pressure--the first number in a blood pressure reading.

Each of the patients took one medication or a placebo for two months before switching to the next treatment. Blood pressure measurements were taken three times over a 24-hour period at the end of each of five treatment periods.

The medications evaluated include a diuretic (hydrochlorothiazide), a beta-blocker (atenolol), an angiotensin converting enzyme (ACE) inhibitor (perindopril), and a calcium channel blocker (felodipine).

Their results are published in the January issue of the American Journal of Hypertension.

The investigation found that diuretics and calcium channel blockers were relatively consistent at lowering blood pressure around the clock, said Morgan. Beta-blockers, on the other hand, lowered daytime blood pressure but had little effect on nighttime blood pressure. ACE inhibitors lowered blood pressure more at night than during the day, Morgan noted.

"Experiments in animals and human observations indicate that nighttime blood pressure elevation is associated with more cardiac enlargement and a higher morbidity and mortality," Morgan told Reuters Health.

As a result, combinations of drugs may need to be used to obtain optimal blood pressure control over a 24-hour interval, according to Morgan.

"The reason that beta blockers may not have as good results as diuretics on complications may result from (its) failure of blood pressure control at night," Morgan added.

Currently, the majority of patients with hypertension are on one drug, Morgan said. However, single drug therapy controls blood pressure in less than 30% of patients, according to the Australian researcher.

"This may explain why control of blood pressure achieved in the community is so poor," he concluded.

SOURCE: American Journal of Hypertension 2003;16:46-50.

In conclusion, blood pressure is controlled by a large number of variables.We recognize this by the individual variation that occurs in response to specific drugs.The evidence from this study those different times of the day may require us to rethink our therapeutic strategies.It is probably an additional reason to use multiple drugs rather than relying on high dose monotherapy



UC Davis Study Identifies C-Reactive Protein as Cause of Blood Clot Formation 
Source: University of California, Davis - Medical Center
Further underscoring the limitations of cholesterol screening in assessing a patient's risk for heart disease, a new study by UC Davis physicians is the first to conclusively link C-reactive proteins (CRP) to formation of blood clots, a major cause of heart attacks, strokes and other vascular disease. Until now, CRP had been recognized mainly as a risk marker of heart disease. The study appears in the January 25, 2003, print edition of the journal Circulation, a publication of the American Heart Association (news - web sites), and is available on the Web at www.circulationaha.org.

"The study provides further conclusive evidence that CRP, until now viewed as an 'innocent bystander' in the formation of heart disease, is in fact a key culprit that causes inflammation in the arteries, resulting in formation of clots and plaque that lead to heart attacks and strokes," said Ishwarlal Jialal, professor of pathology and director of the Laboratory for Atherosclerosis and Metabolic Research at UC Davis School of Medicine and Medical Center.

The study demonstrates that CRP causes cells in the arteries, known as human aortic endothelial cells, to produce higher levels of an enzyme that inhibits the breakdown of clots. The enzyme, plasminogen activator inhibitor-1 (PAI-1) is also a strong risk marker for heart disease, especially in diabetics (news - web sites). The study used a variety of techniques to convincingly show how CRP activates PAI-1 in aortic cells, causing lesions in the arteries that ultimately lead to formation of plaque and blood clots.

The study underscores the need to use CRP screening to more accurately assess at-risk populations, according to Jialal, who is the Robert E. Stowell Endowed Chair in Experimental Pathology.

"Based on these findings, if a patient has normal cholesterol but high levels of CRP, an aggressive course of treatment is recommended to help the patient reduce the risk of heart attack, stroke and other heart diseases," said Jialal. "By relying on cholesterol alone, a physician could significantly underestimate a patient's risk level."

High CRP levels can occur in otherwise healthy individuals, according to the study. Patients with high levels of CRP can reduce risk by losing weight, exercising on a regular basis, stopping cigarette smoking, or taking statin drugs, Jialal added.

The study also closely links CRP and PAI-1 to diabetes and metabolic syndrome, a disorder characterized by a disproportionate amount of abdominal fat, elevated blood pressure, blood sugar and triglycerides and low levels of HDL, the "good" kind of cholesterol.

"In another important discovery, this study shows that in the presence of high blood-glucose levels, CRP is especially active in the stimulation of PAI-1. As a result, the effect of CRP is especially acute for patients with diabetes and metabolic syndrome," said Sridevi Devaraj, a co-investigator and assistant professor of pathology at UC Davis. "Given the current pandemic of obesity which increases one's risk of diabetes, the study's insights about the active role of CRP and PAI-1 in heart disease are especially valuable."

The new study adds to the findings of another landmark study on CRP by Jialal's team at UC Davis that showed CRP actually damages the blood vessel wall by blocking a critical "protector" protein and inhibiting nitric oxide.

"Interestingly, the new study indicates that activation of PAI-1 was unrelated to the nitric oxide inhibition identified in the earlier study," said Jialal. "This indicates that CRP has multiple, independent effects that cause heart disease."

Dan Yan Xu, a physician and postgraduate researcher in the pathology department at UC Davis, also contributed to the study.

This study was supported by grants from the National Institutes of Health (news - web sites), the Juvenile Diabetes Foundation and American Diabetes Association.




NEW YORK (Reuters Health) - Individuals with severe periodontal disease may be prone to releasing endotoxins into their bloodstream, which may help explain the link between gum infections and cardiovascular disease, Belgian researchers report.


Drug Cuts Women's Stroke Risk-Study  By Julie Steenhuysen
CHICAGO (Reuters) - The use of Evista, Eli Lilly and Co.'s drug to treat post-menopausal osteoporosis, cut the risk of stroke by nearly two-thirds in women at high risk for heart disease, researchers said on Sunday.

  The data, presented at the American Heart Association (news - web sites)'s annual Scientific Sessions conference in Chicago, showed that Evista was linked with a 62% reduction in the risk of all strokes--fatal and non-fatal--in post-menopausal women at high risk for heart disease.

The research comes in the wake of recent findings by a Women's Health Initiative study that showed Wyeth's hormone replacement therapy Prempro, which is often prescribed for post-menopausal osteoporosis, increased the risk of stroke by 41%.

The WHI study's results, released in July, triggered a huge debate over how doctors treat post-menopausal women.

Lilly's Evista findings were part of a four-year study of 7,705 post-menopausal women with osteoporosis. It found that of the 1,035 women in the group who were at high risk of heart disease, Evista cut the risk of non-fatal strokes by 68%.

"These data are particularly interesting in light of recent findings from the WHI trial examining hormone therapy," said Dr. Elizabeth Barrett-Connor, professor of family and preventative medicine at the University of California, San Diego, who presented the results. "While raloxifene and hormone therapy are both prescribed for osteoporosis, the WHI data showed that combined estrogen-progestin hormone therapy actually increased the risk of stroke."
A TIME FOR 'SMART' ESTROGEN

Dr. Cheryl Keech, clinical research physician at Lilly, said the Evista results suggest a place for "smart" estrogen therapy that can target specific receptors within a cell.

"The one thing WHI has shown us is you have to do randomized controlled trials," Keech told Reuters.

Known by the chemical name of raloxifene HCI, Evista is a selective estrogen receptor modulator used for both the prevention and treatment of osteoporosis.

Along with the decreased risk of stroke in the subgroup of women at high risk for heart disease, Evista showed no increased risk of stroke among the total 7,705-patient population. Evista also did not increase blood pressure, a risk factor for stroke.

Lilly said it is studying Evista to determine its ability to reduce the risks of serious heart-related events and breast cancer (news - web sites) in post-menopausal women in a number of clinical trials.

In an ongoing 10,000-patient study of Evista in preventing heart disease, Lilly aims to determine whether Evista can have positive benefits without the problems of hormone replacement therapy.

"We don't see any harm and we see both benefits in stroke and coronary," she said, adding that the observations need to be proven in a prospective trial.

The company plans to use the data from that trial as part of a submission to the US Food and Drug Administration (news - web sites) to use Evista as a treatment to prevent heart disease. Early results of that study will be available in 2005.



Cross-Talk Between Iron Metabolism and Diabetes
José Manuel Fernández-Real, Abel López-Bermejo, and Wifredo Ricart
Diabetes 51(8):2348-2354, 2002. © 2002 American Diabetes Association, Inc.

Abstract
Emerging scientific evidence has disclosed unsuspected influences between iron metabolism and type 2 diabetes. The relationship is bi-directional—iron affects glucose metabolism, and glucose metabolism impinges on several iron metabolic pathways. Oxidative stress and inflammatory cytokines influence these relationships, amplifying and potentiating the initiated events. The clinical impact of these interactions depends on both the genetic predisposition and the time frame in which this network of closely related signals acts. In recent years, increased iron stores have been found to predict the development of type 2 diabetes while iron depletion was protective. Iron-induced damage might also modulate the development of chronic diabetes complications. Iron depletion has been demonstrated to be beneficial in coronary artery responses, endothelial dysfunction, insulin secretion, insulin action, and metabolic control in type 2 diabetes. Here, we show that iron modulates insulin action in healthy individuals and in patients with type 2 diabetes. The extent of this influence should be tested in large-scale clinical trials, searching for the usefulness and cost-effectiveness of therapeutic measures that decrease iron toxicity. The study of individual susceptibility and of the mechanisms that influence tissue iron deposition and damage are proposed to be valuable in anticipating and treating diabetes complications.
Introduction
It is increasingly recognized that iron influences glucose metabolism, even in the absence of significant iron overload. In the generalpopulation, body iron stores are positively associated with the development of glucose intolerance, type 2 diabetes,[1-7] and gestational diabetes.[8, 9] Among U.S. adults, men with newly diagnosed diabetes had an odds ratio (OR) of 4.94 (95%confidence interval [CI] 3.05-8.01) and women had an OR of 3.61 (2.01-6.48) of having elevated ferritin concentrations.[6] These figures are especially remarkable when considering the increased prevalence of elevated iron stores in the healthy, free-living U.S. elderly population (28% of men and 12.2% of women showed high iron stores in a recent study).[10]
Frequent blood donations, leading to decreased iron stores, have been demonstrated to reduce postprandial hyperinsulinemia in healthy volunteers,[11] to improve insulin sensitivity,[12] and to constitute a protective factor for the development of type 2 diabetes.[13] Phlebotomy was followed by decreases in serum glucose, cholesterol, triglycerides and a poprotein B,[14] and by improvement in both -cell secretion and peripheral insulin action in patients with type 2 diabetes.[15] A significant impact of tissue iron excess on systemic effects of diabetes is suggested by recent reports in which iron appears to influence the development of diabetic nephropathy and vascular dysfunction. In this sense, intravenous administration of deferoxamine resulted in improved coronary artery responses to cold stress testing in type 2 diabetic subjects[16] and in amelioration of endothelial dysfunction in subjects with coronary heart disease.[17]
All these observations suggest that iron is more intimately linked to human pathophysiology than previously thought. In fact, iron metabolism is closely associated with the clinical presentation of numerous systemic diseases.[18] Tissue iron excess contributes to produce and amplify the injury caused by free radicals as well as to modulate various steps involved in the inflammatory lesion.
In this article, we summarize the relationships between iron, insulin resistance, and type 2 diabetes and discuss the therapeutical and clinical implications of reducing body iron.
Iron Stores are Associated With Insulin Sensitivity, Insulin Secretion, and Type 2 Diabetes
Iron and Insulin Sensitivity
Iron stores, expressed as serum ferritin concentration, have been proposed to be a component of the insulin-resistance syndrome. Indeed, the concentration of circulating ferritin was significantly associated with centrally distributed body fatness as well as with several other measurements of obesity.[19] In the apparently healthy general population, serum levels of ferritin were also positively correlated with baseline serum glucose and with the area under the curve for glucose during the glucose oral tolerance test.[20, 21] In gestational diabetes, both BMI and serum ferritin levels were found to be independent predictors of 2-h glucose during an oral glucose tolerance test.[8, 9] Ferritin levels also correlated with diastolic arterial blood pressure, even after adjustment for BMI. Of note is the beneficial effect of blood letting, a means of reducing iron stores, in the treatment of resistant hypertension[22] and in posttrans plant hypertension associated with erythrocytosis.[23] Serum ferritin concentration was also directly associated with uric acid (another component of the insulin resistance syndrome) and inversely related with HDL cholesterol and the HDL2-to-HDL3 ratio.[21]
Insulin resistance itself, assessed by either the euglycemic clamp [24] or the minimal model,[25, 26] was found to be associated with total body iron stores, even in the presence of normal glucose tolerance. Dmochowski et al.[25] reported that serum concentrations of ferritin were negatively correlated with insulin sensitivity (r = -0.58) in subjects with hemosiderosis. Cavallo-Perinet al.[26] reported that insulin sensitivity, which correlated closely with iron overload (r = -0.70), was reduced by 40% in thalassemia patients. Insulin resistance also appeared to be closely linked to total body iron stores in the general population.[21] Serum ferritin levels could be a useful marker of insulin resistance beyond a given threshold.[20, 21] In the study by Toumainen et al.,[20] the increase in serum insulin concentrations was clearly apparent in the upper two quintiles of ferritin levels. In a different study, the correlation between circulating ferritin and insulin resistance was only observed in the upper two quartiles of ferritin levels.[21] Below this threshold, the potential tissue effects of siderosis would be negligible.
Some comments on the specifity of serum ferritin as an indicatorof iron stores seem necessary. The relationship between serum ferritin and histochemical assessment of stainable tissue iron contributes to define threshold values for serum ferritin, indicating exhausted, small, normal, ample, and increased iron stores. However, the barrier between "normal" and " small" or "ample" iron stores is not well defined and remains controversial. Approximately 10% of type 2 diabetic patients with high ferritin levels had transferrin saturations greater than normal (40%). On the other hand, serum ferritin should be cautiously evaluated in patients with type 2 diabetes, because it may falsely indicate "normal iron stores." It should not be ignored that chronic inflammation could contribute, to some extent, to increased ferritin concentration (see below).
Iron and Beta-cell Function
Recent in vitro studies have shown that H-ferritin mRNA is four-to eightfold higher in rat islets treated with 20 mmol/l glucose than in islets treated with 1 mmol/l glucose.[27] The potential reason for the increased ferritin in the -cell is that ferritin exhibits antioxidant properties and the -cell is particularly sensitive to oxygen radicals. This high amount of ferritin can explain why iron is preferentially retained in the -cell. In fact, iron deposition in islets, albeit variable, is restricted to -cells.[28]
An increase in -cell mass was demonstrated in a small number of nondiabetic or mildly diabetic patients with iron overload.[28] In agreement with this increase in -cell mass, raised basal and stimulated C-peptide secretion were observed in type 2 diabetic patients with increased serum ferritin concentration. Furthermore, significantly lowered C-peptide secretion was found after phlebotomy-induced iron depletion, suggesting increased-cell insulin sensitivity.[15]
Iron Overload and Type 2 Diabetes
Five additional pieces of scientific evidence favor the hypothesis that iron plays a role in type 2 diabetes. First, increased prevalence of hemochromatosis was found among unselected patients with type 2 diabetes. Phelps et al.[29] and Conte et al.[30] reported that diabetes confers increased risk for hereditary hemochromatosis, which was 2.4% and 1.34% higher in Australian and Italian populations, respectively.
This evidence, however, is not always consistent. The recent characterization of HFE has allowed a more direct study of the prevalence of its mutations in type 2 diabetes. Homozygosity for the C282Y change is generally associated with clinically evident hereditary hemochromatosis (83% of hemochromatosis patients are YY homozygotes). Compound heterozygotes for H63D mutation(C282Y/H63D) succumb to the disease, although with reduced penetrance. An increased frequency of C282Y mutations in subjects with type 2 diabetes has been described in some studies.[31-32] Notwithstanding, at least four additional studies reported nosignificant differences in the prevalence of C282Y mutations between patients with type 2 diabetes and control subjects of Caucasian origin.[33-36] In the Spanish population, the frequency of the H63D mutation was significantly higher in type 2 diabetic subjects.[36] The H63D mutation is also associated with other nonclassical conditions of iron overload. On the other hand, it is interesting to mention that genetic hemochromatosis contributed to 1% of late-onset type 1 diabetes.[37]
Second, frequent blood donations, leading to decreasing iron stones, have been demonstrated to constitute a protective factor for the development of diabetes.[13] This finding is especially important given the high prevalence of increased iron stores in the general population of western countries[10] and the observation that increased iron stores appear to predict an increased incidence of type 2 diabetes.[5] In experimental models, the incidence of diabetes was reduced from 78 to 22%at 120 days of age after serial blood withdrawals in the BBrat.[38]
Third, a recent randomized study also suggests that iron stores may influence insulin action in type 2 diabetes.[15] In this report, 28 type 2 diabetic patients with increased serum ferritin concentration and negative for C282Y mutation of hereditary hemochromatosis were randomized to blood letting (three 500ml phlebotomies at 2-week intervals) or to observation. Insulin secretion and sensitivity were tested at baseline and at 4 and 12 months thereafter. The two groups were matched for age, BMI, pharmacological treatment, and chronic diabetes complications.[15] Baseline glycated hemoglobin and insulin sensitivity were not significantly different between the two groups. A statistically significant increase in insulin sensitivity was observed in the blood-letting group (from 2.30 ± 1.81 to 3.08 ±2.55 mg · dl-1 · min-1 at 4 months to 3.16 ±1.85 mg · dl-1 · min-1 at 12 months, P = 0.045) in contrast to patients subjected to observation in whom insulin sensitivity did not significantly change (from 3.24 ±1.9 to 3.26 ± 2.05 mg · dl-1 · min-1 at 4 months to 2.31 ± 1.35 mg · dl-1 · min-1at 12 months). Accordingly, blood HbA1c decreased significantly only in the blood-letting group at 4 months (mean differences-0.61, 95% CI -0.17 to -1.048, P = 0.01).
Fourth, a novel syndrome of hepatic iron overload has been described that associates hyperferritinemia with normal transferrin saturation and is not linked to the HLA-A3 antigen, a common marker for hereditary hemochromatosis.[39] This condition is known as insulin resistance-associated hepatic iron overload (IR-HIO) and combines abnormalities in iron metabolism (isolated hyperferritinemia with normal transferrin saturation), steatohepatitis, and the insulin resistance syndrome (obesity, hyperlipidemia, abnormal glucose metabolism, and hypertension).[39-41] In IR-HIO, iron overload occurs in both hepatocytes and sinusoid cells, being higher in the latter cells in 45% of cases, a finding seen in only 3% of subjects with hemochromatosis.[42] Approximately two-thirds of these patients develop steatosis, whereas the remaining third show isolated signs of inflammation.[42] Thus, these patients are at high risk for developing liver fibrosis, a complication observed in 60% of all cases, even in the presence of moderate iron overload. In contrast, liver fibrosis affects only 33% of patients with hemocromatosis. Because patients with IR-HIO are prone to experience significant tissue damage and because this can be prevented with simple and inexpensive therapies (i.e., phlebotomy), higher awareness in order to diagnose the disease has been suggested.
It cannot be ruled out, however, that IR-HIO is the same process of iron overload-related insulin resistance that associate sliver steatosis and fibrosis in susceptible patients. It is important to recognize that in one study, liver iron stores were found within the normal range in patients with type 2 diabetes[43] in contrast to other studies.[29, 30] Under this assumption, IR-HIO would be at one end of the spectrum of iron overload-related insulin resistance.
Fifth, insulin resistance features are frequently seen in patients chronically infected with the hepatitis C virus. In these subjects, BMI, elderliness, iron stores, and family history of diabetes and advanced liver fibrosis were found to predict the development of diabetes.[44]
Interacting Pathways Linking Glucose and Iron Metabolism
A. Insulin Influences Iron Metabolism
Insulin is an anabolic hormone that stimulates the cellular uptake of many nutrients, including hexoses, amino acids, cations and anions. Intestinal absorption of nonheme iron is tightly regulated in keeping with the body requirements, and absorption of iron is minimal when body iron stores are normal. Absorption of heme iron (largely provided by red meat in western countries) does not appear to be dependent on body iron content. In the steady state, circulating iron is bound to transferrin and is taken up from the blood by a high-affinity specific transferrin receptor. The transferrin-receptor complex is internalized by endocytosis and released into a nonacidic cellular compartment, where it can be used in the synthesis of essential cellular components. Insulin is known to cause a rapid and marked stimulation of iron uptake by fat cells, redistributing transferrin receptors from an intracellular membrane compartment to the cell surface.[45] Insulin is also responsible for the increased ferritin synthesis in cultured rat glioma cells.[46] Importantly, transferrin receptors have been shown to colocalize with insulin-responsive glucose transporters and insulin-like growth factor II receptors in the microsomal membranes of cultured adypocytes, suggesting that regulation of iron uptake by insulin occurs in parallel with its effects on glucose transport.[47]
B. Iron Influences Glucose Metabolism
Reciprocally, iron influences insulin action. Iron interferes with insulin inhibition of glucose production by the liver. Hepatic extraction and metabolism of insulin is reduced with increasing iron stores, leading to peripheral hyperinsulinemia.[48] In fact, the initial and most common abnormality seen in iron overload conditions is liver insulin resistance.[49]There is some evidence that iron overload also affects skeletal muscle,[50] the main effector of insulin action.
C. Oxidative Stress Influences Both Glucose and Iron Metabolism
Oxidative stress induces both insulin resistance [by decreasing internalization of insulin[51]] and increased ferritin synthesis.
Iron is intimately linked to oxidative stress. Iron participates, through the Fenton reaction, in the formation of highly toxic free radicals, such as hydroxide and the superoxide anion, which are capable of inducing lipid peroxidation. For iron to act as a prooxidant agent, it must be in its free form. Iron can be released from ferritin by the action of reducing agents that convert Fe3+ into Fe2+.[52] Glycation of transferrin decreases its ability to bind ferrous iron[53] and, by increasing the pool of free iron, stimulates ferritin synthesis. Glycated holotransferrin is additionally known to facilitate the production of free oxygen radicals, such as hydroxide, that further amplify the oxidative effects of iron.[53]
The fraction of nonused and highly toxic iron is stored as ferritin molecules in order to be neutralized. Apoferritin, the protein fraction of ferritin, is spatially folded to create a central groove that holds oxidized iron molecules [Fe3+]. apoferritin is a high-molecular weight (450 kDa) multimeric protein (24subunits of heavy and light chains) that exhibits exquisite high capacity for iron storage (4, 500 mol iron per mole of ferritin). Synthesis of apoferritin is induced at both the transcriptional and posttranscriptional levels by the presence of free iron. The increase in Fe2+ down regulates the affinity of iron-regulatory element (IRE) binding protein (BP) for its IRE binding site in the 5' region of ferritin mRNA, leading to increased ferritin translation.
The heavy chain in the apoferritin molecule exerts ferroxidase activity, catalyzing the oxidation of Fe2+ into Fe3+, which prevents iron-induced cyclic red-ox reactions that would spread and amplify the oxidative damage. This activity occurs underaerobic conditions, allowing the storage of intracellular iron. When concentrations of antioxidants are low, the reducing potential and anaerobiosis progressively increase, facilitating a rapid release of iron from ferritin. Additionally, the ferroxidase activity in the heavy chain is down regulated in this setting, decreasing the incorporation of iron into ferritin. The overall result of oxidative reactions is an increase in the availability of free iron from the ferritin molecule as well as from other molecules undergoing degradation, such as the heme group. These events, in turn, can enhance and amplify the process of generation of free radicals, causing cellular and tissue damage. The oxidative stress also down regulates the affinity of IRE for IRE-BP. Thus, ferritin can act both as a source or iron, which induces oxidative stress, and as a mechanism that protects against iron toxicity.[54]
Hyperferritininemia is present in 6.6% of unselected patients with type 2 diabetes.[55] Serum concentrations of ferritin are usually increased in poorly controlled type 1 and type 2diabetic subjects, and ferritin has been shown to predict HbA1c independently of glucose,[21] probably reflecting increase doxidative stress. Short-term improvement in glycemic control is followed by variable decreases in serum ferritin concentration.
D. Cytokines Influence Iron and Glucose Metabolism
Cytokines simultaneously cause an increase in transferrin receptors on the cell surface, favoring tissue deposition of iron[56] and insulin resistance.[57]
In summary, a scenario can be envisioned in which the physiological action of insulin leads to increased uptake of different nutrients and iron. Any factor causing hyperinsulinemia (weight gain, aging, repeated usual-life infections, or periodontitis) amplifies this process, determining increased deposition of iron, which in the long-term worsens insulin resistance.
Clinical and Therapeutical Implications of Iron Depletion
A. Iron Depletion and Diabetic Metabolic Control
There are historical notes regarding iron overload conditions that can be helpful in delineating the effects of iron depletion.[58-60] Phlebotomy was first used in the treatment of hemochromatosis in the 1950s. Interestingly, diabetic metabolic control improved in 35-45% of patients with hemochromatosis after iron depletion.[58] In 1969, Williams et al.[59] showed that diabetic patients treated with phlebotomy required less insulin than similar patients during the prephlebotomy period. In 1972, Dymock et al.[60] reported a significant reduction in total daily insulin dosage following phlebotomy.
Facchini[11] found significant reductions in insulin concentrations 1 month after performing a 550-ml phlebotomy in healthy volunteers. It has also been suggested that the increased insulin sensitivity observed in vegetarian subjects might be related to their low-iron diet. Recently, as stated above, blood letting of 1, 500 ml has been demonstrated to improve insulin sensitivity and to decrease C-peptide secretion in type 2 diabetic subjects who were negative for common hemochromatosis mutations but had increased serum ferritin concentration.[15]
Iron chelators also seem beneficial in optimizing diabetic metabolic control. In 1989, Cutler[61] administered deferoxamine to nine type 2 diabetic patients with hyperferritinemia who were negative for the most common hemochromatosis haplotypes. Major improvement in the metabolic control was observed in seven patients, and parallel reductions in baseline concentrations of glucose, triglycerides, and glycated hemoglobin were observed. Treatment with either insulin or oral hypoglycemic agents could be discontinued insome patients.[61] Subsequently, it was reported that subcutaneous deferoxamine caused an improvement in glycated hemoglobin in another nine patients,[62] although serum concentrations of C-peptide after glucose or arginine infusion did not improve significantly.[62]
B. Iron Depletion and Chronic Diabetes Complications
Macrovascular Disease. The general effect of catalytic iron is to convert poorly reactive free radicals, such as H2O2, into highly reactive ones, such as OH- and O2. Free radicals and other oxidation by-products are well known factors that impair the mechanisms of vasodilatation[63] and cause endothelial depletion of endogenous antioxidants, such as ascorbic acid.[64] Iron chelation blocks oxidation of LDL, and iron released from heme and ferritin favors oxidation of this lipoprotein.[65] Increased iron availability is, theoretically, expected to contribute to macrovascular disease because iron has an adverse effect on endothelium[66] and accelerates the development of atherosclerosis.[67] In fact, ferritin gene expression increases in the course of atherosclerotic plaque formation.[68] Notwithstanding, studies performed in experimental models offer conflicting conclusions. For instance, an iron-deficient diet has been found to reduce atherosclerotic lesions,[69] whereas iron overload led to a decrease in atherosclerosis[70] in the same animal model. It should be noted, however, that the possible influence of obesity, insulin resistance, or diabetes has not been explored in experimental iron-modified atherosclerosis. Moreover, humans are the only species in which genetic iron overload has been described to induce significant parenchymal damage.[71]
In subjects with hemochromatosis, medium-sized arteries are characterized by an eccentric hypertrophy and decreased distensibility that are partially reversible after iron depletion.[72] These findings seem to be linked to iron-induced fibrogenesis, determining an increased total collagen content in arteries from these patients. There is also some evidence for iron-dependent growth of arterial wall tissue: iron chelation by deferoxamine inhibits vascular smooth muscle cell proliferation.[73]
Long-term use of the modified iron chelator hydroxyethyl starch conjugated-deferoxamine prevented endothelial dysfunction associated with experimental diabetes.[74] In type 2 diabetic patients, coronary artery responses to cold stress testing improved substantially after deferoxamine administration.[16] Similarly, iron chelation was shown to ameliorate the endothelial dysfunction of patients with coronary heart disease.[17]
Improvement of nitroglycerine-induced vasodilatation was also observed following phlebotomy in type 2 diabetic patients in a preliminary study. The improvement in vascular reactivity paralleled the decrease in serum transferrin saturation, total hemoglobin (markers of circulating iron), and blood glycated hemoglobin.[75] These observations suggest that diabetic vascular dysfunction seems partially reversible and that the circulating compartment acts as a reservoir of transition metals that directly affects vascular function.[76] Increased hemoglobin, an iron-enriched protein, is deleterious for endothelial function, as normal blood vessels exposed to total and glycated hemoglobin are known to experience impaired vascular relaxation.[77]
In the general population, the relationship between iron and atherosclerosis is, however, controversial.[78] Thus, some animal experimental data regarding the effect of manipulating iron stores on atherosclerosis and human data showing improvement of vascular structure and function following iron depletion[16, 17, 72, 75] are both consistent with the theory that iron contributes to the development of vascular disease. However, the current epidemiological data associating iron stores with either atherosclerosis or coronary heart disease (reviewed i[78] do not fully support this hypothesis.
Diabetic Nephropathy
An early development and accelerated course of diabetic nephropathy has been observed in iron-loaded patients with -thalassemia, a condition with recognized iron overload.[79] Increased proximal tubular lysosomal iron concentration has been observed in patients with diabetic nephropathy.[80] These observations are pertinent to the finding that mutations for hereditary hemochromatosis appeared to predict the development of diabetic nephropathy.[32]
Diabetic Neuropathy
Deferoxamine administration restored motor and sensory nerve conduction velocity and improved nerve blood flow in experimental studies.[76] The possible extrapolation of these findings to human diabetes has not been explored.
Conclusions
The central role of iron in biology is illustrated by the fact that this is the fourth most abundant element in Earth’s crust as well as the transition element most abundant in living organisms. Iron has additionally proven to be fundamental in the selection imposed by evolution, given its close relationship with oxygen. Although loses of this metal are only a tenth of those found in any other given mammal, iron regulation is maintained within very narrow limits in humans.[71]
Our biochemistry and physiology are tuned to life conditions that existed before the advent of agriculture some 10, 000 years ago. Hunter-gatherer societies obtained more than 56-65%of their subsistence from animal foods.[81] Meat eaters, with a typical high protein and low- carbohydrate diet, have a significant higher plasma concentration of iron[82] and concomitant insulin resistance in the liver and peripheral tissues.[83] It is plausible that the survival advantage of both iron and high protein-induced insulin resistance in our ancestral line was that the little available glucose from carbohydrate consumption was preserved for brain function and reproductive fetal/placental/mammary tissues.[84] Nowadays, with increased life expectancy, this protective mechanism has become detrimental, with iron promoting both insulin resistance and increased oxidative stress.
In the last decades, the impact of transition metals, in general, and iron, in particular, on human physiology has begun to be elucidated. Because iron is a first-line prooxidant, it contributes to regulate the clinical manifestations of numerous systemic diseases, including diabetes and atherosclerosis. Iron regulation of the cell oxidative stress can explain, at least in part, its close association with abnormalities in insulin sensitivity (see Figure 1 for a summary of iron interactions with insulin sensitivity).

Figure 1. Schematic representation of iron interactions with insulin resistance and oxidative stress. Insulin influences iron metabolism. Insulin stimulates ferritin synthesis and facilitates iron uptake by the cell through the translocation of transferrin receptors from the intracellular compartment to the cell surface. Conversely, iron influences glucose metabolism. Iron in a potent prooxidant that increases the cell oxidative stress, causing inhibition of insulin internalization and actions, results in hyperinsulinemia and insulin resistance. Free iron also exerts a positive feedback on ferritin synthesis, while oxidative stress increases the release of iron from ferritin. The increased oxidative stress and insulin resistance cause endothelial and tissue damage. Protein glycation, as seen in diabetes, further amplifies these abnormalities stimulating iron release from transferrin, increasing the cell oxidative stress and directly causing endothelial and tissue damage. NO, nitric oxide; TR, transferrin receptor; (+), stimulation; (-), inhibition; dotted lines, possible trafficking or iron through the cell membrane.
The clarification of the mechanisms that regulate this interaction are proposed to contribute to improve the management of diabetes and to anticipate its possible complications. Here, we show that iron modulates insulin action in healthy individuals and in patients with type 2 diabetes. The extent of this influence should be tested in large-scale clinical trials, searching for the usefulness and cost-effectiveness of therapeutic measures that decrease iron toxicity. Of paramount importance will be the definition of "normal body iron stores" and the establishment of early therapeutical interventions. Simple and inexpensive therapies, such as blood letting and iron chelators, are emerging as alternative and effective treatments for insulin resistance.
It will also be necessary to explore whether important elements of iron metabolism are altered in diabetes, namely the transporters DMT1, ferroportin, and MTP1, which are critical in intestinal absorption and entry of iron into the circulation, and haephastin, which oxidizes Fe2+ to Fe3+ during this process.[85] Interestingly, certain genes appear to be simultaneously involved in iron balance, inflammation, and glucose responsiveness, suggesting a link between these pathways and type 2 diabetes.[85]
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Linoleic Acid Intake May Cut Stroke Risk: Study
Thu Aug 1, 5:25 PM ET
NEW YORK (Reuters Health) - Consuming foods rich in linoleic acid--a fatty acid found in corn, sunflower and safflower oils and soybeans--may protect a person from the most common type of stroke, new study findings suggest.
   
Ischemic strokes, which occur when a clot or narrowed artery cuts off the blood supply to part of the brain, account for about 80% of all strokes. The other 20% are due to broken blood vessels in the brain and are called hemorrhagic strokes.
Lead author Dr. Hiroyasu Iso of the University of Tsukuba in Ibaraki-ken, Japan, and colleagues followed 7,450 men and women aged 40 to 85 for a period of 6 to 14 years. At the start of the study each person answered questions about their daily food intake and gave a blood sample that was later evaluated for levels of linoleic acid.
At the end of the study period, 122 people had an ischemic stroke and 75 had hemorrhagic strokes, according to the report published in the August issue of Stroke: Journal of the American Heart Association ( news - web sites).
"The major finding of the present study was that (levels of blood) linoleic acid was inversely associated with the risk of total stroke, ischemic stroke and more specifically lacunar infarction"--a type of stroke that involves small arteries deep in the brain, according to Iso and colleagues.
The investigators report that a 5% increase in consumption of linoleic acid was associated with a 28% decrease in total stroke risk, a 34% decrease in ischemic stroke, a 37% reduction in lacunar stroke and a 19% reduction in hemorrhagic stroke.
Iso's team notes that linoleic acid may decrease blood pressure and reduce the blood's ability to "stick" together, or form clots.
"This finding implies the potential importance of dietary intake of linoleic acid for the prevention of ischemic stroke. A clinical trial is necessary to confirm the causality between linoleic acid intake and risk of ischemic stroke," the authors conclude.
SOURCE: Stroke 2002;33.



Many Methods to Reduce Blood Pressure
Source: American Diabetes Association
Publication date: 2002-07-02
The New York Times
July 2, 2002
By JANE E. BRODY
Three decades after the National High Blood Pressure Education Program started saying that controlling high blood pressure saves lives, rates of hypertension are rising.
In addition, the proportion of patients being treated — or treated well enough to bring their blood pressure readings under control — is falling, creating waves of alarm among cardiovascular specialists.
As a result, stroke rates are going up and the decline in heart attacks has leveled off; both strokes and heart attacks are directly linked to uncontrolled hypertension.
In trying to account for these changes, experts point to a number of factors. One is the sharp increase in the percentage of Americans who are overweight or obese, creating for themselves the leading risk factor for hypertension.
Another is a basic quality of the condition: it is a silent disease, and a vast majority of people with it feel fine, even as it causes life-threatening or fatal damage. About 30 percent of people with hypertension don't know they have it.
A third factor is the unwillingness or inability of most people with high blood pressure to change their diets and try exercise and relaxation techniques that can bring their readings down to normal.
Fourth is the reluctance of many patients to take medications and the failure of many doctors to keep up with drug developments that would allow them to design individual treatments and prescribe the remedies likely to produce the most benefit with the fewest side effects.
Further complicating the picture are the insurance-dictated constraints on doctors. Many of them don't take the time to educate patients about the importance of continually monitoring their pressure readings.
Last but hardly least, the drug companies with the greatest financial interest in getting all people with hypertension into treatment may have had a detrimental effect on the acceptance of drug therapy.
At the expense of older, less expensive drugs, pharmaceutical companies have heavily promoted newer and more expensive medications that may not always be the best for a particular patient. These may also be too costly for many older patients, who, since Medicare does not pay for drugs, have been known to take half the prescribed dosages to stay within their budget.
Tailoring Treatment
There are six classes of medications and scores of different drugs and drug combinations that are tailored to control high blood pressure.
Which drug or drug combination is right is determined by factors like sex, age, systolic blood pressure (the higher number, representing the pressure on arteries when the heart beats), smoking habits, total cholesterol, level of protective H.D.L. cholesterol, and whether the patient has diabetes or an enlarged left ventricle, the heart's main pumping chamber.
The simplest remedy that achieves the desired goal is the best choice. For example, say most experts, among them Dr. Steven A. Dosh of Escanaba, Mich., patients who have no known underlying disease are best treated initially with diuretics, which bring blood pressure down by reducing the volume of fluid the heart has to pump to outlying tissues. Diuretics in low doses are well tolerated, safe, effective and cheap and need be taken only once a day.
But, as Dr. Dosh wrote recently in The Journal of Family Practice, for those who have already had a heart attack or are otherwise known to have coronary artery disease, beta-blockers, which slow the heart and reduce the force of its contractions, may be the initial drug of choice. When combined with a diuretic, beta-blockers were proved to be especially good at preventing strokes, though less effective than expected in preventing heart attacks, according to Dr. Michael Alderman, a hypertension specialist at Albert Einstein Medical Center in the Bronx.
But one newer, more expensive drug may be better for some patients. For example, for patients with diabetes or systolic hypertension after a heart attack, the best remedy may be ACE, or angiotensin-converting enzyme, inhibitors. They relax blood vessels by reducing production of angiotensin I, which is converted into angiotensin II, a hormone that constricts arteries.
If an ACE inhibitor's side effects — a cough and a rash — are troublesome, a patient could try an A.R.B, or angiotensin receptor blocker, which prevents the action of angiotensin II. Thus far, the A.R.B.'s appear to be more effective than beta-blockers in preventing strokes, though the drugs are equally effective in reducing blood pressure, Dr. Alderman said.
The other classes are vasodilators, which relax blood vessels, and calcium channel blockers, which also relax blood vessels but in a number of studies have been linked to an increased risk of cardiovascular disease, especially congestive heart failure. However, studies have also indicated that long-acting calcium channel blockers may be more effective at preventing strokes than the ACE inhibitors, Dr. Alderman said.
So far, neither the ACE inhibitors nor the calcium channel blockers have been shown to be better than diuretics in preventing heart attacks, he added.
What Should a Patient Do?
First, don't do what one woman in her 50's did. Having experienced swollen ankles and a rapid heart beat as a side effect of a calcium channel blocker prescribed for hypertension, she stopped taking the drug and never returned to the doctor.
All drugs have side effects, a fact especially troublesome for blood pressure treatment, since the disorder itself usually produces no symptoms. Diuretics in high doses force patients to the bathroom many extra times a day and several times a night.
Many diuretics also deplete the body of potassium and magnesium and may raise blood levels of cholesterol and glucose. Beta-blockers in full dose can make people groggy, slow the heart rate and cause bronchial spasms.
Vasodilators can cause headaches, fluid retention and rapid heart rate. ACE inhibitors commonly cause an annoying dry cough, whereas the A.R.B.'s, which are generally better tolerated, may cause high blood levels of potassium. And nearly all the antihypertensive medications can inhibit sexual function, particularly in men.
Dr. Alderman suggested that in many patients, the ideal treatment is a combination of low doses of two or more drugs. This has the advantage of limiting the likelihood of disturbing side effects while increasing the drugs' effectiveness.
Patients should be closely monitored in the first months of treatment and every six months afterward; if the treatment is or becomes ineffective, it must be changed, by increasing the dose or changing drugs. Home blood pressure monitoring can alert patients to the need to see a doctor.
And for any drug treatment to work optimally, otherwise healthy patients should also adopt protective habits, including eating diets rich in fruits, vegetables and low-fat dairy products and low in fat and salt and other sources of sodium.
Aerobic exercise for at least 45 minutes a day three times a week is highly recommended. And, if the patient is overweight, a loss of 10 percent of total body weight can be very beneficial. Relaxation exercises like meditation may also help.
Publication date: 2002-07-02
© 2002, YellowBrix, Inc.

Antioxidants Battle InflammationSource: American Diabetes Association Publication date: July 14, 2002
High-fat meal raises blood's proinflammatory factors; vitamins E and C counter that response
In a series of studies designed to define the role of dietary macronutrients in the initiation of arterial inflammation that predisposes a person to atherosclerosis, University at Buffalo researchers have found that a high intake of glucose, or eating a high-fat, high-calorie, fast-food meal causes an increase in the blood's inflammatory components.
However, they also have shown that the antioxidant vitamins E and C can nullify this inflammatory response.
Results of the research were presented in San Francisco, California at the June 2002 annual meeting of the American Diabetes Association. "A meal high in calories and fat caused an increase in inflammatory markers that lasted 3-4 hours," said Paresh Dandona, MD, professor of medicine, head of the University of Buffalo School of Medicine and Biomedical Sciences' Division of Endocrinology, and senior author on the studies.
"We think the influx of macronutrients may alter cell behavior and that genes are activated to produce more powerful enzymes and mediators that are potentially more damaging to the lining of blood vessels. Obese persons may have an ongoing abnormality of the white blood cells and the lining of blood vessels.
"On the other hand, we found that one way to render an 'unsafe' meal 'safe' is to include antioxidant vitamins," Dandona said. "The proinflammatory effect of glucose is stopped if right at the outset you give vitamins E and C."
The "meal" study was conducted with nine normal subjects who ate a 900-calorie breakfast - an egg-and-ham sandwich and hash browns from a fast-food restaurant - after an overnight fast. Blood samples were taken before eating and at 1, 2 and 3 hours after eating to determine the concentration of oxygen free radicals, which can begin the inflammation cascade by injuring blood vessel linings, and of several blood mediators of inflammation.
Results showed a mean increase of free radicals over baseline of 129%, 175% and 138% at the three sampling times, respectively. Levels of several proinflammatory indicators also increased significantly, while the level of a factor that inhibits inflammation was reduced.
Four additional studies further defined the proinflammatory cascade initiated by an influx of glucose alone and of an infusion of fatty acids. These studies also showed that both sugar and fat caused a reduction in the ability of vessels to expand and contract in response to changes in blood flow, actions crucial for maintaining healthy blood pressure and blood flow to vital organs.
In yet another study, eight subjects took 1200 I.U. of vitamin E and 500 mg of vitamin C before a glucose challenge, and on a subsequent occasion, took only glucose. Blood samples were taken before the challenges and at 1, 2, and 3 hours after.
Results showed that levels of oxygen free radicals and two proinflammatory markers increased when glucose was taken alone, but did not increase when accompanied by the two antioxidant vitamins.
This article was prepared by Heart Disease Weekly editors from staff and other reports.
www.NewsRx.net
Publication date: 2002-07-09
© 2002, YellowBrix, Inc.

Aspirin For Ulcer Patients
People who have both heart disease and ulcers may be able to
safely take a daily aspirin to prevent heart attacks and strokes.
A study from Hong Kong finds that a taking a heartburn drug may
prevent stomach problems caused by low-dose aspirin. In the
study, researchers looked at 123 people with heart problems who
had been taken off of aspirin therapy because of bleeding ulcers.
All of the people were infected with Heliobacter pylori, the
bacteria that cause many ulcers. After receiving antibiotics for
the H. pylori infection, the participants went back on aspirin
therapy. Half of them also took the prescription heartburn
medication Prevacid, while the rest got a placebo. After one
year, only one of the people taking Prevacid had started bleeding
from the stomach again, compared to nine of the people taking the
placebo, The Associated Press reports.  The study was published
in the New England Journal of Medicine.

How Exercise Protects the Heart
Mon Jun 24, 6:35 PM ET
NEW YORK (Reuters Health) - Women who are more physically fit may have lower levels of inflammation in their bodies--and, therefore, a lower risk of heart attack--than those who exercise less, according to researchers.
   
This finding suggests that the benefits of exercise on the heart may, in fact, stem from its ability to reduce inflammation within blood vessels, a supposed risk factor for heart attack, the authors note.
"The health benefits from enhanced fitness may have an anti-inflammatory mechanism," Dr. Michael J. LaMonte of the University of Utah in Salt Lake City and colleagues write.
LaMonte and his team investigated the effect of exercise on inflammation by comparing a woman's fitness to her blood levels of a substance known as C-reactive protein (CRP), which is a marker for inflammation.
The body releases CRP as part of its response to infection and injury. During infection, for instance, blood CRP levels temporarily soar as the immune system jumps into action. More subtly, chronic CRP elevations have been linked to an increased risk of heart disease, and inflammation is believed to play a key role in the hardening and narrowing of arteries that can lead to heart attack and stroke.
In this study, the authors did not measure a woman's fitness by simply asking her how much she exercised, for those reports are often inaccurate. Rather, LaMonte and his team determined how in shape a woman was by testing her stamina on a treadmill. While each woman was on the treadmill, the machine sped up and increased its elevation periodically during the test. The authors measured how long each woman could keep exercising on the machine, with those lasting the longest designated as the most physically fit.
The researchers tested fitness and CRP levels in 135 African-American, Native-American, and white women.
Reporting in the recent issue of Circulation: Journal of the American Heart Association, LaMonte and his team found that Native-American women and whites who were the most physically fit also had the lowest levels of CRP in their blood. Surprisingly, the authors did not detect a link between CRP blood levels and exercise stamina in African-American women.
African-American women had the highest levels of CRP in their blood, with an average of 0.43 milligrams per deciliter of blood, contrasted with the 0.25 and 0.23 milligrams per deciliter measured in the blood of Native-American and white women, respectively.
CRP levels also varied according to a woman's body mass index (BMI), a measurement of obesity that factors in height and weight. Women with normal BMIs exhibited the lowest levels of CRP in their blood, while those who were considered obese had the highest CRP levels.
Low levels of CRP have been associated with a lower risk of developing diabetes, the authors note, and the anti-inflammatory benefits of exercise may be responsible for that effect, as well.
"Higher fitness levels appear to have an anti-inflammatory effect that may be a mechanism for lowering [heart disease] and type 2 diabetes," LaMonte and his colleagues conclude.
SOURCE: Circulation: Journal of the American Heart Association 2002;106.

SYNDROME X
Hidden Heart Disease
Researchers may have discovered a cause of one "hidden" form of
heart disease. A study published in the New England Journal of
Medicine suggests that irregular blood flow in tiny arteries in
the heart wall may be behind the puzzling condition known as
"syndrome X." People with syndrome X experience chest pain, or
angina, but their tests show none of the classic signs of heart
disease, The Associated Press reports. This has raised medical
debate over whether the condition is a form of heart disease or a
neurological problem, the AP says. Now, British researchers have
evidence suggesting that syndrome X is a cardiovascular problem.
In the study, the researchers performed magnetic resonance
imaging (MRI) tests on 20 people with syndrome X and 10 healthy
people. The MRIs showed that the people with syndrome X had too
little blood flowing in the inner heart wall and too much in the
outer layer. The researchers say the problems with blood
movement in the heart arteries could be due to faulty biochemical
signaling or minute spasms, the AP reports. However, there is no
evidence that this condition actually raises a person's risk of
having a heart attack or other cardiac problem, the researchers
say.

FISH OIL FOR ARRYTHMIAS
Previous studies have suggested that fish oil supplements may reduce the risk of an additional heart attack or stroke in patients who have recently experienced a heart attack. Now new study findings reveal that the supplement may also reduce the risk of sudden death. The findings show that this reduced risk was evident after as few as 3 months, which seems to support the hypothesis that adding n-3 polyunsaturated fatty acids (PUFAs)--commonly found in fish and fish oil--to a healthy diet may lower the risk of fatal arrhythmia, an irregular heartbeat that in severe cases can lead to cardiac arrest, the authors report. "Reduction of sudden death appeared early after start of treatment," lead study author Dr. Roberto Marchioli, of Consorzio Mario Negri Sud in Italy, told Reuters Health. This "seems to support the idea that (the benefits of PUFAs) could be due to an anti-arryhythmia effect," he added. The study included 11,323 patients who had suffered a heart attack within the previous 3 months. All of the patients received the same preventive care and ate Mediterranean-style diets rich in fruits, vegetables, olive oil and fish. But some patients also consumed 1 gram of the fish oil supplements per day. During the 3.5-year follow-up period, 1,031 individuals died, Marchioli and his colleagues report in the April issue of the Circulation: Journal of the American Heart Association. Patients who took the fish oil supplements appeared to be at a 41% lower risk of death from any cause after only 3 months of treatment, study findings indicate. After 4 months of treatment, these patients also appeared to be at a significantly reduced risk of sudden cardiac death. And by the end of the study period, patients treated with fish oil supplements were 45% less likely to die suddenly from a heart-related cause, Marchioli and his colleagues report. In light of the findings, Marchioli said that the benefit of fish oil supplements "seems to be additive to the benefit that can be obtained by standard preventive treatment." "One capsule of a fish oil concentrate daily for 3.5 years resulted in a very significant reduction in sudden cardiac death. Thus, a simple and safe change in diet can potentially produce a large public health benefit," editorialist Dr. Alexander Leaf of Harvard Medical School in Boston, Massachusetts, told Reuters Health. "Individuals who have known coronary heart disease or a family history of coronary heart disease among immediate relatives would be prudent to heed the recent advice of the American Heart Association to eat two or more meals of oily fish per week or take a daily supplement of fish oil capsules," Leaf added.
Eating oily fish cuts heart attacks
Studies suggest fatty oils can reduce risk of cardiac deaths up to 30 percent.By David Brown / Washington Post

BOSTON -- Two new studies show that both men and women who eat substantial amounts of oily fish are greatly protected from fatally abnormal heart rhythms.
The studies -- which both draw their conclusions from long-term observation of tens of thousands of people -- greatly bolster the evidence that eating fish regularly can have major health benefits.
While most of earlier studies involve only men, one of the new studies demonstrates fish's benefit in women.
Although ocean-living, cold-water oily fish such as salmon, swordfish and tuna offer the largest easily accessible source of beneficial n-3 fatty acids, there are others. Flax seed oil, canola oil, and English walnuts all contain significant amounts of the oils.
Scientists in both studies said that while eating fish is good advice, people shouldn't jump to the conclusion that fish-oil supplements are an equivalent or a substitute.
One Brigham and Women's Hospital study, which appears in today's Journal of the American Medical Association, found that the more frequently a woman ate fish, the less likely she was to suffer a heart attack or die of any cardiac cause.
Specifically, those who ate fish three times a month had a 30 percent lower risk of heart attack or death as those who never ate fish. Eating fish five times a week was only slightly more beneficial; those women had a 34 percent lower risk. Similar trends were seen in estimations of n-4 fatty acids in the diet.
The study was based on the experience of 85,000 women nurses, beginning in 1976.
Each year, about 220,000 Americans experience sudden death, collapsing and dying within an hour, often before they get to a hospital. In most cases, an abnormal heart rhythm arising from existing heart disease is believed to be the cause. In about 50 percent of cases, however, the sufferer is unaware he or she has heart disease. There's no chest pain or previous heart attack. Instead, sudden death is the first symptom of their problem.
"Prevention is really the only way to impact the rate and mortality from sudden death," said Christine Albert, a cardiologist at Brigham and Women's Hospital in Boston, who headed a second study. "One way you could do it in a population that's healthy is through diet and lifestyle."
In Albert's study, published in this week's New England Journal of Medicine, researchers looked at the experience of about 22,000 male doctors who enrolled in the Physicians' Health Study in 1982. They were all free of heart disease at the time, and about 15,000 also volunteered a blood sample.
Over the next 17 years, 94 of the men who'd given blood samples and who hadn't subsequently been diagnosed with heart disease died suddenly. The researchers chose about 180 surviving members of the study and compared them with those victims. In particular, they compared the bloodstream concentrations of substances called n-3 fatty acids, found primarily in fish oils.
On average, the men who died had lower amounts of n-3 fatty acids than the ones who hadn't died suddenly. When the researchers divided all the men into four groups based on the concentration of n-3 fatty acids in the blood, the men in the highest quarter had only one-fifth the risk of sudden death as those in the lowest quarter.
The researchers used dietary information gathered in five interviews between 1980 and 1994 to estimate fish intake. They also calculated the approximate amount of n-3 fatty acid consumed, based on the type of fish the women listed in their diet questionnaires.
The nurses' study also showed that the primary effect was in reducing sudden death, although the risk of having a heart attack was also lower in fish-eaters.
Terry Jacobson, a physician at Emory University who has studied the effects of fish oils on heart disease, said he believes the new studies "have large public health implications." He added, however, that before fish-oil can be used as preventive medicine in healthy people, a study needs to be done in which people are randomly assigned to either get the oils or a placebo.
He said he plans to propose such a study to the National Institutes of Health in the near future. He said at least 6,000 people would need to be enrolled and observed for at least three or four years.
A European study published in 1999 showed that fish-oil supplements reduced the risk of sudden death in people who'd already suffered a heart attack. The n-3 fatty acids appear to have a specific antiarrhythmic effect, possibly by stabilizing membranes of heart muscle cells.
The oils also have a blood-thinning effect similar to aspirin. In some observational studies, fish consumption has been associated with a lower risk of stroke. There have been anecdotal observations that fish-oil supplements may have anti-depressant effects, as well.




Top Blood Pressure Number Key for Gauging Risk
     NEW YORK, Mar 11 (Reuters Health) - The top number in a blood pressure reading is the best way to determine a man's heart attack and stroke risk, and should be used to guide treatment, according to a new report. But many doctors continue to treat patients based on the lower number, and the study authors believe this practice should change.
     The top number measures systolic blood pressure, the force on blood vessel walls during a heart beat. The bottom, or diastolic, number gauges pressure when the heart is at rest between beats. High blood pressure, or hypertension, is defined as a systolic reading of 140 millimeters of mercury (mm Hg) or greater or a diastolic reading of 90 mm Hg or above.
     The diastolic number has conventionally been viewed as a more sensitive indicator of hypertension, and is the reading that commonly influences clinical decision-making regarding degree of disease present and what therapeutic steps should be taken.
In the current study, lead author Dr. Athanase Benetos of the Institut de la Sante et de la Recherche Medicale in Paris, France, and colleagues found that patients with uncontrolled systolic blood pressure were almost 2.5 times more likely to die of heart disease than patients with controlled blood pressure.
     But risk of death from cardiovascular disease was not associated with diastolic blood pressure, the investigators report in the March 11th issue of the Archives of Internal Medicine.
"The most important result of this study is that cardiovascular mortality, especially coronary heart disease mortality, is much higher in uncontrolled hypertensive men than in controlled hypertensive men, and that systolic blood pressure levels, but not diastolic blood pressure levels, can predict coronary vascular disease risk independent of age," the authors write.
The study also revealed that 85.5% of men being treated for high blood pressure had uncontrolled systolic or diastolic blood pressure, or both. These patients had a 66% greater risk of death associated with heart disease than those men with controlled blood pressure.
"This clearly confirms that, as measured in a clinical setting, a controlled blood pressure, especially systolic blood pressure, is uncommon," Benetos and colleagues write.
     Nevertheless, the authors emphasize that treating systolic blood pressure is of greater value than treating diastolic blood pressure since it has been shown to be a better predictor of death from heart disease. "Our results show that in clinical practice a well-controlled systolic blood pressure (less than 140 mm Hg) should be the goal of antihypertensive treatment," the researchers conclude.
"As advised in the recent recommendations of the National High Blood Pressure Education program, it is crucial for healthcare providers to focus on systolic blood pressure for diagnosis, staging and therapeutic strategy in hypertension, particularly in the elderly," Dr. Prakash C. Deedwania of the University of California, San Francisco, writes in an editorial accompanying the study.
"It is also important to emphasize that often more than one, but usually two or three drugs are needed to achieve optimal control of systolic blood pressure," he adds.
SOURCE: Archives of Internal Medicine 2002;162:506-508, 577-581.
Blood Pressure On Top
New research confirms that the top number in a blood pressure
reading is more useful than the bottom number in determining
heart disease risk. Doctors have typically looked at diastolic
pressure (the bottom number) to assess whether people are at risk
for heart disease, but a study published in the Archives of
Internal Medicine adds to growing evidence that it's systolic
blood pressure (the top number) that matters most. In the study,
researchers looked at 4,714 French men, whose average age was 52,
for a period of 14 years. They found that during that period,
men with systolic blood pressure of 160 or higher had more than
twice the risk of death from heart disease compared to men with
systolic blood pressure of less than 140. Systolic pressures
between 140 and 160 were associated with a slightly increased
risk. The diastolic pressure reading did not appear to have any
effect on heart disease risk. Although earlier studies suggested
that high systolic blood pressure was an important risk factor
for elderly people, the new study shows that it is also important
in middle-aged people, The Associated Press reports. An optimal
blood pressure reading is 120 over 80 or lower.



The New England Journal of Medicine:   March 14, 2002
Exercise Capacity and Mortality
  In this study, more than 6000 men, some with and some without cardiovascular disease, underwent treadmill exercise testing and were followed for six years. Exercise capacity, as measured in metabolic equivalents, was a strong predictor of overall mortality, whether or not there was clinical evidence of cardiovascular disease.

The findings, which demonstrate a strong association between reduced exercise capacity and higher mortality, are subject to two different interpretations. One is that reduced exercise capacity is simply a marker of a higher risk of death. The other is that reduced exercise capacity is part of the chain of causation and that increasing physical fitness through regular exercise may reduce mortality.


Antibiotics May Prevent Second Heart Attack
Mon Mar 11, 5:34 PM ET
By Merritt McKinney
NEW YORK (Reuters Health) - Treatment with antibiotics may reduce the risk of heart attack and chest pain in some patients with heart disease, according to the results of a new study.
   
In a study of 148 patients who experienced a heart attack or an episode of severe, heart-related chest pain, those who took a 3-month course of the antibiotic clarithromycin were 41% less likely to have another cardiovascular "event" during the next year and a half than patients who received an inactive (placebo) pill.
"Antibiotics seem to be a beneficial option" for patients with coronary heart disease, the study's lead author, Dr. Juha Sinisalo of Helsinki University Central Hospital in Finland, told Reuters Health.
But the Finnish researcher cautioned that the results are preliminary. "Larger studies are needed before this treatment can be justified for routine use," Sinisalo said.
One potential problem with using antibiotics to treat heart attack patients is that such widespread use of the drugs could increase the rate at which bacteria become resistant to antibiotics, Sinisalo noted. If antibiotics were to be used to treat heart attack in large numbers of people, "it would be better to limit the use to one certain group of antibiotics," according to Sinisalo. Widespread use of several different types of antibiotics could lead to more antibiotic resistance, the researcher explained.
Inflammation plays a role in both heart attacks and unstable angina  a type of heart-related chest pain that occurs when a person is at rest. Recently, more and more attention has been paid to the idea that infections may contribute to this inflammation.
Based on the potential link between infections and the inflammation involved in heart disease, investigators have tried to find out whether clearing infections with antibiotics can benefit heart disease patients. So far, the results of these studies have not been conclusive.
Unlike other studies that tested the effectiveness of short-term antibiotic treatment, Sinisalo's team evaluated the effects of a 3-month course of the antibiotic clarithromycin. The study included patients who had had a severe heart attack or unstable angina. The findings will be published in the April 2nd issue of Circulation: Journal of the American Heart Association
Patients treated with the antibiotic were 41% less likely to have another heart attack, unstable angina or other type of cardiovascular event. The apparent beneficial effect of clarithromycin began while patients were taking the drug, but this effect did not diminish after the patients stopped taking it.
The researchers suspect that most of the benefits were due to clarithromycin's antibacterial effect. They note that a bacterium called Chlamydia pneumoniae, which is targeted by clarithromycin, can produce inflammation in blood vessels. But the authors point out that clarithromycin may have affected other infections, too. In addition, the antibiotic has a direct anti-inflammatory effect, which could have accounted for some of the benefits, they note.
SOURCE: Circulation 2002;105.


HIGH BLOOD PRESSURE-SOME QUICK FACTS
Approximately 60 million Americans are affected by cardiovascular disease.[1] Since the beginning of the 20th century, cardiovascular disease has consistently been the leading cause of death in the United States despite numerous advances in treatment. In 1998, approximately 1 million people died of cardiovascular disease. Hypertension and heart failure are the first and fifth most common causes of cardiovascular disease, affecting 50 million and 5 million Americans, respectively. The estimated economic burden resulting from hypertension and heart failure exceeds $60 billion/year.[2] In addition, hypertension is the leading cause of heart failure and end-stage renal disease. Despite increased awareness and treatment of hypertension, only 27% of Americans with hypertension achieve modest control (blood pressure < 140/90 mm Hg), according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.[3] Hypertension is present in 75% of patients with heart failure, and from 1979-1998 heart failure deaths increased 135%.[2]


Effects of an Angiotensin-Converting–Enzyme Inhibitor, Ramipril, on Cardiovascular Events in High-Risk Patients
New England Journal Article  Volume 342:145-153  January 20, 2000  Number 3
Discussion:
Our findings show that ramipril, an angiotensin-converting–enzyme inhibitor, is beneficial in a broad range of patients without evidence of left ventricular systolic dysfunction or heart failure who are at high risk for cardiovascular events. Treatment with ramipril reduced the rates of death, myocardial infarction, stroke, coronary revascularization, cardiac arrest, and heart failure as well as the risk of complications related to diabetes and of diabetes itself.
Our findings indicate that the spectrum of patients who would benefit from treatment with an angiotensin-converting–enzyme inhibitor is quite broad and complement those of previous studies of patients with low ejection fractions3 or heart failure and acute myocardial infarction.7 The underlying rationale for our study was that the inhibition of angiotensin-converting enzyme would prevent events related to ischemia and atherosclerosis, in addition to those related to heart failure and left ventricular dysfunction (although patients with these two conditions were excluded from the study). We therefore included a broad range of patients with any manifestation of coronary artery disease (e.g., a history of myocardial infarction or revascularization, unstable angina, or stable angina), a history of cerebrovascular disease or peripheral vascular disease, or diabetes and one cardiovascular risk factor, and ramipril was beneficial in all these subgroups.
A total of 3577 patients in our study had diabetes, 1135 of whom had no clinical manifestations of cardiovascular disease, and the event rate in this group was about half that in the other patients (10.2 percent vs. 18.7 percent). Nonetheless, overall, treatment with ramipril was beneficial in patients with diabetes.
The magnitude of the benefit of treatment with ramipril with respect to the primary outcome was at least as large as that observed with other proven secondary prevention measures, such as treatment with beta-blockers,8 aspirin,9 and lipid-lowering agents,10 during four years of treatment. In addition, there were reductions in the rates of revascularization, heart failure, complications related to diabetes, and new cases of diabetes. The rapid and sustained response to ramipril and the continuing divergence in results between the ramipril group and the placebo group indicate that longer-term treatment may yield even better results. Ramipril was also well tolerated.
The benefits of ramipril were observed among patients who were already taking a number of effective treatments, such as aspirin, beta-blockers, and lipid-lowering agents, indicating that the inhibition of angiotensin-converting enzyme offers an additional approach to the prevention of atherothrombotic complications. Only a small part of the benefit could be attributed to a reduction in blood pressure, since the majority of patients did not have hypertension at base line (according to conventional definitions) and the mean reduction in blood pressure with treatment was extremely small (3/2 mm Hg). A reduction of 2 mm Hg in diastolic blood pressure might at best account for about 40 percent of the reduction in the rate of stroke and about one quarter of the reduction in the rate of myocardial infarction.11 Howev-er, the results of recent studies, such as the Hypertension Optimal Treatment study,12 suggest that for high-risk patients (e.g., those with diabetes), it may be beneficial to lower blood pressure even if it is already within the "normal" range. Moreover, a recent reanalysis of 20 years of blood-pressure data from the Framingham Heart Study13 suggests that the degree of benefit expected from a decrease in blood pressure may have been underestimated. Despite these considerations, it is likely that angiotensin-converting–enzyme inhibitors exert additional direct mechanisms on the heart or the vasculature that are important. These may include antagonizing the direct effects of angiotensin II on vasoconstriction,1 the proliferation of vascular smooth-muscle cells,1 and rupture of plaques14; improving vascular endothelial function1; reducing left ventricular hypertrophy; and enhancing fibrinolysis.1
We also observed a reduction in the incidence of heart failure in patients with no evidence of impairment of left ventricular systolic dysfunction. These data complement those of a study of patients with a low ejection fraction15 and studies of patients after myocardial infarction,1,2,3,7,16,17 which demonstrated that treatment with angiotensin-converting–enzyme inhibitors prevents heart failure, and the studies of patients with documented low ejection fractions and heart failure, which indicated that angiotensin-converting–enzyme inhibitors reduced the rate of hospitalization for heart failure.17 Both these results and our findings suggest that angiotensin-converting–enzyme inhibitors will be beneficial for patients who are at high risk for heart failure, irrespective of the degree of left ventricular systolic dysfunction.
We believe that the extent to which our results may have been affected by the inclusion of patients with undiagnosed low ejection fractions is very small, because a large substudy of 496 consecutive patients at three centers indicated that only 2.6 percent had an ejection fraction of less than 0.40, an extensive review of charts identified only 8.1 percent of patients with a low ejection fraction before randomization, and treatment was clearly beneficial in the subgroup of 4772 patients who were documented to have preserved ventricular function (relative risk, 0.73; 95 percent confidence interval, 0.63 to 0.84; P<0.001) and in those with no history of myocardial infarction (relative risk, 0.77; 95 percent confidence interval, 0.65 to 0.91; P=0.002).
We observed a marked reduction in the incidence of complications related to diabetes and new cases of diabetes. These effects may be mediated by improved insulin sensitivity, a decrease in hepatic clearance of insulin, an antiinflammatory effect, improved blood flow to the pancreas,18 or an effect on abdominal fat.19 The results are also consistent with the results of the recent Captopril Prevention Project study,20 which indicated a lower rate of newly diagnosed diabetes in patients who were randomly assigned to receive captopril than in those who were assigned to receive a diuretic or beta-blocker, and with the results of other trials, which reported that treatment with an angiotensin-converting–enzyme inhibitor slowed the progression of nephropathy among patients with type 2 diabetes21 as well as those without diabetes.22
Our findings clearly demonstrate that ramipril, a long-acting angiotensin-converting–enzyme inhibitor, reduces the rates of death, myocardial infarction, stroke, revascularization, cardiac arrest, heart failure, complications related to diabetes, and new cases of diabetes in a broad spectrum of high-risk patients. Treating 1000 patients with ramipril for four years prevents about 150 events in approximately 70 patients.

Funded by the Medical Research Council of Canada, Hoechst–Marion Roussel, AstraZeneca, King Pharmaceuticals, Natural Source Vitamin E Association and Negma, and the Heart and Stroke Foundation of Ontario. Dr. Yusuf was supported by a Senior Scientist Award of the Medical Research Council of Canada and a Heart and Stroke Foundation of Ontario Research Chair. We are indebted to N. Bender, B. Rangoonwala, A. Ljunggren, G. Olsson, W. Whitehill, J.C. Dairon, J. Ghadiali, B. Carter, J.P. St. Pierre, W. Schulz, M. Jensen, L. Rios-Nogales, M. Bravo, J. Bourgouin, C. Vint-Reed, and F. Schutze for support and to Karin Dearness for secretarial help. * The investigators are listed in the Appendix.


C-reactive protein, serumPathology Associates of Lexington, P.A.  our  pathology group
is the first of the "acute phase reactant" proteins to increase during states of acute inflammation and is exclusively produced in the liver. CRP elevation is thought to correlate with endothelial dysfunction6. The plasma level can double every 8 hours, peaking in 50 hours; upon removal of the stimulus, CRP drops rapidly, having a 5-7 hour half life1. In the post-shock (trauma, sepsis, etc.) period, the body swings into a catabolic phase and makes acute phase reactants at the expense of such proteins as prealbumin and albumin7.
More recently, related to theories that CRP is a surrogate reflector of part of the pathogenesis of coronary artery obstructive lesions, it has been noted that risk of future acute myocardial infarction (AMI) is increased in persons with sustained levels of CRP above 2.0 mg/L. This "cardio-CRP" screen (CRP-H...high-sensitivity CRP...hs-CRP, detect down to about 0.1 mg/L) should, like lipid profiles, be done only during periods of good health, free from any recent minor or major illnesses. NOTE: tests at different times in the same non-sick person may vary by about 30%4.
Some (clinical chemist, Nader Rifai, of Harvard) feel that hs-CRP is the single best predictor of future cardiovascular disease risk (those with CRP levels in the upper 25% are 3 times as likely to suffer a heart attack). Sustained elevations are also predictive of increased stroke and peripheral vascular disease risk. In healthy adults, 75% of hs-CRP values are < 0.32 mg/L3. The median normal concentration of CRP is 0.8 mg/L, with 90% of apparently healthy individuals having a value less than 3 mg/L and 99% less than 12 mg/L1. Our lab's "normal" is <0.2 mg/dl (2 mg/L).
And, different methodology in different labs will likely not relate exactly to published quintile and quartile information6...therefore, risk categorization should be viewed somewhat loosely.
situations with CRP within normal range:
lowest cardio-risk quintile (quintile #1) is < 0.55 mg/L
low-mid cardio-risk (quintile #2) is 0.55-0.99 mg/L
mid-high cardio-risk (quintile#3) is 1.0-2.1 mg/L
even such smoldering important but non-acutely threatening active chronic infections as gingivitis and periodontitis can cause elevations into one of the higher quintiles
a normal CRP is highly unlikely in the face of a significantly acutely threatening bacterial infection1
in evaluating a patient with "fever and night sweats", the signs and symptoms are almost certainly NOT due to hidden infection when CRP is in normal range (therefore, could be malignant lymphoma)
detecting supervening infection after "clean" surgery: a potentially valuable marker to serially follow after surgery...in search of early detection of postoperative, initially occult (hidden) infection. Clean CRP pattern: begin increase from baseline in 4-6 hours postop & peaks at (usually to intermediate elevations) 48-72 hours, begins to decrease after 72 hours and back near baseline by 5th-7th postop day.5
situations with CRP elevations:
with cardio-risk in mind, values greater than 15 mg/L suggest that the screening effort is confounded by recent or acute inflammatory disease beyond what could be expected related to coronary artery disease6; post-shock (trauma, sepsis) catabolic phase can highly elevate CRP7
those with troponin-normal cardiac events who have hs-CRP >3 mg/L at discharge have increased risk of major event within the next 3 months and, if >5 mg/L on admission, an increased risk of a major event on out for 6 months6
hi-risk cardio-risk (quintile #4) is 2.1-3.8 mg/L
highest cardio-risk zone (quintile #5), is from 3.9-15 mg/L
even such smoldering important but non-acutely threatening active chronic infections as gingivitis and periodontitis can cause elevations into one of the higher quintiles
hs-CRP predicts a future stroke, AMI, or PVD event in males & females, smokers & nonsmokers, when in the highest quartile at a relative risk over "normals" of 2-fold, 3-fold, and 4-fold, respectively.
hs-CRP joined with TC:HDL-C ratio gives strongest predictive information6
estrogen replacement therapy (HRT or ERT) increases CRP level6; obesity, smoking, and vitamin B6 deficiency will each cause CRP "elevations" (probably meaning as to cardio-risk quintiles)
minor elevations1: SLE, scleroderma (systemic sclerosis), dermatomyositis, ulcerative colitis, leukemia, GVHD (graft vs. host disease)
major serum/plasma elevations:1
infections
   
CSF CRP reported to increase in bacterial, not viral5
hypersensitivity complications of infections
   
rheumatic fever
erythema nodosum
inflammatory disease
   
rheumatoid arthritis
juvenile chronic arthritis
ankylosing spondylitis
psoriatic arthritis
systemic vasculitis syndromes
polymyalgia rheumatica
Reiter's disease
Crohn's disease
familial Mediterranean fever
allograft rejection
   
kidney & marrow (not heart)5
malignant but not benign tumors5
   
carcinoma (breast, lung, GI)5
lymphoma
sarcoma
necrosis
   
acute myocardial infarction (AMI)
tumor embolization
acute pancreatitis
trauma
   
burns
fractures
bacterial vs. viral infection: a very high level (>100 mg/L) more likely bacterial than viral, while intermediate levels (10-50 mg/L) can be either viral or bacterial
postoperative elevations, especially when they can be concretely related to a normal or reasonably low-elevated preoperative CRP baseline test value, tend to be reflective of infection and not just organizing resolution of clean-surgical tissue damage
monitoring extent & therapeutic response to inflammatory disease:
postoperative "dirty case" monitor
is the infection responding to the antibiotic (pyelonephritis, pelvic infections, osteomyelitis, meningitis, endocarditis)? CRP not affected by drugs or fever suppressants1.
detection and management of intercurrent infections: in lupus, ulcerative colitis, Crohn's disease, a major rise above usual baseline CRP level suggests an infection1
References:
Hunter Area Pathology Services information sheet, Nov. 2001 [site]
Specialty Labs manual, Jan 2001.
Mayo Medical Lab manual, Jan 2001.
Serum Markers of Risk for Coronary Artery Disease, Plaut D, Advance for ...., 10(11):41-44, Nov. 2001.
Interpretation of Diagnostic Tests, Wallach, 2000, 7th Ed., pages 843-847.
Rafai & Ridker, Clinical Chemistry, 47(3):403-411, 2001
Proteins Used in Nutritional Assessment, Spiekerman AM, Clinics In Lab. Medicine 13(2):353-369, June 1993..
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Statins and preventative cardiology
Implications of HPS
What impact will the results of HPS have on the practice of preventive cardiology or on the use of statins? Clearly, HPS adds considerable strength to the already impressive foundation of statin literature. While we await publication of the final results, we can also anticipate years of reports that will come from this database. However, there of course will be more immediate effects on clinical practice. Assuming that the final data are similar to what was presented at the AHA meeting, the clinician may feel that clinical trial evidence is now available to support what was already a common practice among more aggressively treating physicians - the use of statins in post-MI patients with average-to-low LDL-C levels (< 125-130 mg/dL).
Perhaps another critical impact of HPS will be the choice of first-line drug therapy among diabetes patients, who often have average-to-low LDL-C levels, low HDL-C levels, and modestly to significantly elevated triglycerides. Although many physicians have been prescribing statins in such scenarios, in fact the only available evidence prior to HPS was from the Veterans Affairs HDL Intervention Trial (VA-HIT)[4] using the fibric acid gemfibrozil (Lopid). In that study, patients with mean LDL-C 110 mg/dL, HDL-C 32 mg/dL, and triglycerides 160 mg/dL who received Lopid 600 mg twice a day had a significant decrease in cardiovascular end points. This was not due to LDL-lowering, since those levels rose some 4 points, HDL rose 6 mg/dL, and triglycerides fell circa 25%. Not surprisingly, among patients with such numbers, 25% were diabetic and as many as 50% may have been insulin resistant. Although we must await the final HPS results for such diabetes patients, especially in terms of their baseline lipids and subsequent lipid changes, statins may well become first-line therapy in this group as well.
This widely pervasive effect of statins on outcomes led the AHA-designated discussant, Dr. Salim Yusuf,[5] McMaster University, Toronto, Ontario, Canada, to suggest that there may no longer be a need to check a lipid profile prior to initiation of a statin. Although this may not have been the consequence that HSP's leader, Dr. Rory Collins, intended to convey, it warrants comment, given its citation by various clinicians in discussion after the session.
Even with the widespread benefits apparently seen in HPS, lipid profiles remain of value. They allow the clinician to gauge risk, important information that may also guide therapy and help motivate the patient in other areas that have independent benefits, eg, diet and exercise. A lipid profile allows the physician to decide the degree of LDL-lowering needed, which may help with selection of the statin, as well as a basis in terms of follow-up. It also provides the physician with information regarding other aspects of the patient's dyslipidemia, ones that can represent additional targets for reducing risk, eg, raising HDL or lowering triglycerides. HPS does not eliminate the ongoing interest in improving HDL while lowering LDL, for example, through the use of combination therapy. The interest in doing so persists, given the obvious fact that simvastatin-treated patients in HPS were certainly not cured and events continued to happen.


NEW ENGLAND JOURNAL ARTICLE ON MRI OF HEART
Volume 345:1863-1869  December 27, 2001  Number 26
Coronary Magnetic Resonance Angiography for the Detection of Coronary Stenoses

W. Yong Kim, M.D., Ph.D., Peter G. Danias, M.D., Ph.D., Matthias Stuber, Ph.D., Scott D. Flamm, M.D., Sven Plein, M.D., Eike Nagel, M.D., Susan E. Langerak, M.Sc., Oliver M. Weber, Ph.D., Erik M. Pedersen, M.D., Ph.D., Matthias Schmidt, M.D., René M. Botnar, Ph.D., and Warren J. Manning, M.D.
ABSTRACT

Background An accurate, noninvasive technique for the diagnosis of coronary disease would be an important advance. We investigated the accuracy of coronary magnetic resonance angiography among patients with suspected coronary disease in a prospective, multicenter study.

Methods Coronary magnetic resonance angiography was performed during free breathing in 109 patients before elective x-ray coronary angiography, and the results of the two diagnostic procedures were compared.

Results A total of 636 of 759 proximal and middle segments of coronary arteries (84 percent) were interpretable on magnetic resonance angiography. In these segments, 78 (83 percent) of 94 clinically significant lesions (those with a 50 percent reduction in diameter on x-ray angiography) were also detected by magnetic resonance angiography. Overall, coronary magnetic resonance angiography had an accuracy of 72 percent (95 percent confidence interval, 63 to 81 percent) in diagnosing coronary artery disease. The sensitivity, specificity, and accuracy for patients with disease of the left main coronary artery or three-vessel disease were 100 percent (95 percent confidence interval, 97 to 100 percent), 85 percent (95 percent confidence interval, 78 to 92 percent), and 87 percent (95 percent confidence interval, 81 to 93 percent), respectively. The negative predictive values for any coronary artery disease and for left main artery or three-vessel disease were 81 percent (95 percent confidence interval, 73 to 89 percent) and 100 percent (95 percent confidence interval, 97 to 100 percent), respectively.

Conclusions Among patients referred for their first x-ray coronary angiogram, three-dimensional coronary magnetic resonance angiography allows for the accurate detection of coronary artery disease of the proximal and middle segments. This noninvasive approach reliably identifies (or rules out) left main coronary artery or three-vessel disease.

http://www.americanheart.org/Scientific/statements/1997/endoasc.htm

Impact of High-Normal Blood Pressure on the Risk of Cardiovascular Diseas

Ramachandran S. Vasan, M.D., Martin G. Larson, Sc.D., Eric P. Leip, M.S., Jane C. Evans, Ph.D., Christopher J. O'Donnell, M.D., M.P.H., William B. Kannel, M.D., M.P.H., and Daniel Levy, M.D.
ABSTRACT
Background Information is limited regarding the risk of cardiovascular disease in persons with high-normal blood pressure (systolic pressure of 130 to 139 mm Hg, diastolic pressure of 85 to 89 mm Hg, or both).

Methods We investigated the association between blood-pressure category at base line and the incidence of cardiovascular disease on follow-up among 6859 participants in the Framingham Heart Study who were initially free of hypertension and cardiovascular disease.

Results A stepwise increase in cardiovascular event rates was noted in persons with higher base-line blood-pressure categories. The 10-year cumulative incidence of cardiovascular disease in subjects 35 to 64 years of age who had high-normal blood pressure was 4 percent (95 percent confidence interval, 2 to 5 percent) for women and 8 percent (95 percent confidence interval, 6 to 10 percent) for men; in older subjects (those 65 to 90 years old), the incidence was 18 percent (95 percent confidence interval, 12 to 23 percent) for women and 25 percent (95 percent confidence interval, 17 to 34 percent) for men. As compared with optimal blood pressure, high-normal blood pressure was associated with a risk-factor–adjusted hazard ratio for cardiovascular disease of 2.5 (95 percent confidence interval, 1.6 to 4.1) in women and 1.6 (95 percent confidence interval, 1.1 to 2.2) in men.

Conclusions High-normal blood pressure is associated with an increased risk of cardiovascular disease. Our findings emphasize the need to determine whether lowering high-normal blood pressure can reduce the risk of cardiovascular disease.


Source Information

From the Framingham Heart Study, Framingham, Mass. (R.S.V., M.G.L., E.P.L., J.C.E., C.J.O., D.L.); the Cardiology Section (R.S.V.) and the Department of Preventive Medicine and Epidemiology (R.S.V., M.G.L., J.C.E., W.B.K., D.L.), Boston University School of Medicine, Boston; the Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston (C.J.O.); the Divisions of Cardiology and Clinical Epidemiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston (D.L.); and the National Heart, Lung, and Blood Institute, Bethesda, Md. (C.J.O., D.L


Antibiotics For Heart Attacks
Popping an antibiotic pill after a heart attack may help heart
patients prevent further attacks. A study presented at the
European Society of Cardiology in Stockholm finds that heart
patients who are given antibiotics have a 40 percent lower chance
of further heart problems than patients who don't take
antibiotics. Some researchers have suspected that infection with
the bacteria chlamydia pneumoniae or heliobacter pylori may cause
the inflammation found in atherosclerosis patients, The
Associated Press reports. This study looked at 324 patients
admitted to the hospital with severe angina or a first heart
attack. About half these patients were found to be infected with
either chlamydia pneumoniae or H. pylori bacteria, the AP says.
The patients were divided into three groups, with one group
receiving a week's worth of the antibiotic axitromycin, the
second receiving a week of amoxycillin and the third getting
dummy pills. A year later, the researchers found that patients
who had received either of the antibiotics were doing better than
patients who got a placebo. The antibiotics appeared to help
even patients who had not tested positive for the bacterial
infections, the AP says. However, the AP quotes experts who say
that larger-scale studies are needed before antibiotics can be
used to treat heart patients. They note than increasing
antibiotic use raises the risk that more bacteria will become
antibiotic-resistant.
For more on heart health, go to: http://www.intelihealth.com/IH/ihtIH/WSIHW000/8059/8059.html

Heart Attack Warning Signs
Some heart attacks are sudden and intense - the "movie heart attack," where no one doubts what's happening. But most heart attacks start slowly, with mild pain or discomfort. Often the people affected aren't sure what's wrong and wait too long before getting help. Here are some of the signs that can mean a heart attack is happening.
Chest discomfort. Most heart attacks involve discomfort in the center of the chest that lasts more than a few minutes, or that goes away and comes back. It can feel like uncomfortable pressure, squeezing, fullness or pain.

Discomfort in other areas of the upper body. Symptoms can include pain or discomfort in one or both arms, the back, neck, jaw or stomach.

Shortness of breath. This feeling often comes along with chest discomfort. But it can occur before the chest discomfort.

Other signs: These may include breaking out in a cold sweat, nausea or lightheadedness.
If you or someone you're with has chest discomfort, especially with one or more of the other signs, don't wait longer than a few minutes (no more than 5) before calling for help. Call 9-1-1…Get to a hospital right away.
Calling 9-1-1 is almost always the fastest way to get lifesaving treatment. Emergency medical services staff can begin treatment when they arrive - up to an hour sooner than if someone gets to the hospital by car. The staff are also trained to revive someone whose heart has stopped. You'll also get treated faster in the hospital if you come by ambulance.
If you can't call 9-1-1, have someone drive you to the hospital right away. If you're the one having symptoms, don't drive yourself, unless you have absolutely no other option.


Stroke Warning Signs
The American Stroke Association says these are the warning signs of stroke:

New Evidence for Stroke Prevention
Scientific Review
Sharon E. Straus, MD; Sumit R. Majumdar, MD; Finlay A. McAlister, MD 
Context Stroke is a major cause of morbidity and mortality, and the application of evidence for stroke prevention varies considerably.
Objective To review the most recent, high-quality evidence for primary and secondary stroke prevention.
Data Sources and Study Selection Searches of MEDLINE, The Cochrane Library, and the ACP Journal Club were performed to identify English-language articles published from 1998 to 2001 that focused on primary and secondary stroke prevention. The references of each retrieved article were scanned, and experts in the field were contacted to identify additional relevant articles.
Data Extraction Each of the articles was appraised, and its quality was graded with levels of evidence based on specific scientific methods that affect a study's validity.
Data Synthesis
For primary prevention of stroke, adequate blood pressure reduction, and treatment of hyperlipidemia, use of antithrombotic therapy in patients with atrial fibrillation and of antiplatelet therapy in patients with myocardial infarction are effective and supported by evidence from several randomized trials. Effective strategies for the secondary prevention of stroke include treatment of hypertension and hyperlipidemia, antithrombotic therapy for patients with atrial fibrillation, antiplatelet therapy, and carotid endarterectomy in patients with severe carotid artery stenosis.
Conclusions Stroke is a major public health concern, and a significant body of evidence supports many primary and secondary prevention strategies.
JAMA. 2002;288:1388-1395
Author/Article Information
Author Affiliations: Division of General Internal Medicine, University Health Network, University of Toronto, Toronto, Ontario (Dr Straus); and Division of General Internal Medicine, University of Alberta, Edmonton (Drs Majumdar and McAlister).

Corresponding Author: Sharon E. Straus, MD, Department of Medicine, University Health Network, Toronto General Hospital, 200 Elizabeth St, ENG 248, Toronto, Ontario, Canada M5G 2C4 (e-mail: sstraus@mtsinai.on.ca).
Reprints are not available from the author.
Funding/Support: Dr Straus is supported by a Career Scientist Award from the Ontario Ministry of Health and Long-Term Care, Drs Majumdar and McAlister are Population Health Investigators of the Alberta Heritage Foundation for Medical Research, and Drs Straus and McAlister are funded by the Canadian Stroke Network.
Financial Disclosure: Dr Straus was coinvestigator on an unrestricted scientific grant from Organon.


Scientific Review and Clinical Applications Section Editor: Wendy Levinson, MD, Contributing Editor. We encourage authors to submit papers to "Scientific Review and Clinical Applications." Please contact Wendy Levinson, MD, Contributing Editor, JAMA; phone: 312-464-5204 begin_of_the_skype_highlighting              312-464-5204      end_of_the_skype_highlighting; fax: 312-464-5824; e-mail: wendy.levinson@utoronto.ca.

Waist Circumference Helps Predict Cardiovascular Risk
Fri Oct 11,11:51 PM ET
By Amanda Gardner
HealthScoutNews Reporter
FRIDAY, Oct. 11 (HealthScoutNews) -- If you want to determine your risk for cardiovascular disease, maybe you should throw out your scale and grab the measuring tape.
   
A study appearing in a recent issue of the American Journal of Clinical Nutrition (news - web sites) suggests waist circumference is more strongly associated with cardiovascular risk factors than body mass index (BMI).
"There's been some research that shows that it may not be the total amount of fat in your body but where it is stored. In other words, fat distribution," says Stanley Heshka, a co-author of the study and a research associate at the New York Obesity Research Center at St. Luke's Roosevelt Hospital in New York City.
Body mass index (the measure of body fat based on height and weight) is the most widely used gauge to tell if adults are overweight or obese. The problem is that it doesn't take into account the wide range of fat distribution found in people.
Meanwhile, various studies have found body fat distribution is a better predictor for many diseases.
In the new study, the researchers looked at information on white men and women gathered for NHANES III, the National Health and Nutrition Examination Survey, which collected data on the health and nutrition of 9,019 Americans. Then the researchers correlated BMI values of 25 and 30 (which indicate overweight and obese, respectively) with cardiovascular and diabetes risk factors. They set out to determine what waist circumferences have the same degree of risk for cardiovascular disease and diabetes as the BMI guidelines.
To minimize the risk of heart disease, men should not go above a 35-inch waist and women should not go above 33 inches, Heshka says. Men whose waists are 39 inches or more and women whose waists are 37 inches or more should lose weight -- and inches, he says.
Though the study data involved exquisitely precise measurements (taken just above the top of the hip bone and at the end of a normal exhalation), regular folks don't need to be quite that exact.
If you come close to the recommended cutoff points, though, you need to take them seriously, Heshka cautions.
The researchers are still working to figure out why girth may be a better predictor of risk for cardiovascular disease. It may be because the amount of fat around the waist reflects more fat inside the abdominal cavity, something that has been associated with coronary vascular disease, Heshka says.
Some people have hypothesized that the fat drains into the portal vein and is then distributed to areas most sensitive to the development of cardiovascular disease.
"No one really knows how the fat works," Heshka says.
Heshka is quick to add that waist circumference alone may not be the best measure to determine cardiovascular disease risk.
Heshka and other researchers are now trying to see what combination of measures (for example, height, weight, waist circumference, body frame size…) are the best predictors for the development of cardiovascular disease.
"We may find that waist circumference and BMI in combination have an even stronger association," Heshka says. "That's what the goal is now: To find optimal predictors so we can find those people at risk."
More data is also needed to confirm that people with large waists are also the ones who eventually develop cardiovascular disease.

Treating Hypertension  WITH ACE INHIBITORS. 
This prospective, open-label, randomized study compared the outcomes in hypertensive subjects 65 to 84 years of age who received therapy with angiotensin-converting–enzyme (ACE) inhibitors or diuretic agents. The rate of cardiovascular events or death from any cause was lower among male subjects who received ACE inhibitors.

Treating hypertension in older persons with an ACE inhibitor may confer an advantage over a diuretic in terms of outcome, despite similar reductions of blood pressure. The difference may be particularly evident among men.
Related Editorial   
Not infrequently, on release of the results of major multicenter trials, the lay press promulgates an immediate response before physicians have had time to assess the peer-reviewed paper. By the next morning, physicians are greeted by a multitude of messages containing frantic questions from patients about how the reported results relate to their particular problems. When the report deals with a common disease (such as hypertension), the magnitude of the public's anxieties is intensified. Moreover, when results appear to conflict with those of a previous study, not infrequently described as "landmark," there is potential for mass confusion and loss of confidence in individual health care providers, exacerbated by media reports that pose this rhetorical question: "Just what are we to believe?"

In this issue of the Journal, Wing et al.1 report the results of a major trial comparing the effects of angiotensin-converting–enzyme (ACE) inhibitors with the effects of diuretics on the rate of cardiovascular events in elderly hypertensive patients. The investigation, the Second Australian National Blood Pressure Study (ANBP2), involved 6083 patients who were followed by 1594 family practitioners for a median of 4.1 years. Numbers of patients and the design and conduct of the study appear reliable, but some of the results contradict those of another major trial, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).2 ALLHAT was designed to compare the diuretic chlorthalidone with agents representing each of three other classes of antihypertensive drugs (ACE inhibitors, calcium antagonists, and alpha-adrenergic–receptor inhibitors) and involved more than 42,000 patients from the United States and Canada. The trials should therefore be comparable. But ANBP2 indicates that ACE inhibitors have an outcome advantage over diuretics (particularly among older men), whereas ALLHAT concluded that diuretics were more effective for blood-pressure control, as well as in terms of outcomes. So what are we to believe?

First, we should consider the sources. Both trials were sponsored and supervised by national health research institutions with academic participation and without commercial influence. A second issue might be whether the drugs studied in each class were equivalent. The honest answer is that we do not really know. ANBP2 used hydrochlorothiazide as the diuretic, whereas ALLHAT used chlorthalidone. Hydrochlorothiazide has an excellent track record and was used as the diuretic in most early trials of antihypertensive therapy; chlorthalidone is equally well accepted. However, there have been no head-to-head trials comparing the efficacy of and outcomes with these two diuretics. In addition, ANBP2 used enalapril as the ACE inhibitor, whereas ALLHAT used lisinopril. Again, questions may be raised, since it is possible that one agent may have a greater effect not only on blood pressure, but also on local renin–angiotensin systems that may affect disease outcomes.3 There have not been (nor are there likely to be) head-to-head comparisons of the long-term efficacy of and outcomes with the two ACE inhibitors. We may also ask whether these were the only drugs used to control blood pressure in these trials. The answer to this question is equivocal. In both trials, other antihypertensive medications were frequently required to achieve blood-pressure goals, and the use of these additional agents also compounds the complexities of any comparison between the trials.

All of these are straightforward questions whose answers could explain the differences between the conclusions. There are also some more complex questions. Which agent controlled blood pressure better? The ANBP2 report indicates that there were similar reductions in blood pressure in the two treatment groups, whereas in ALLHAT, the diuretic-based regimen was more efficacious (as indicated both by the blood pressures and by the percentage of patients in whom the blood-pressure goal was achieved). We may well ask why there was a difference in blood pressure if the participating physicians were allowed to achieve the goal with the addition of the other classes of antihypertensive drugs.

What about clinical outcomes? Again, we must equivocate, because the trials used vastly different definitions of primary and secondary outcomes. The primary outcome in ANBP2 was the total number of fatal and nonfatal cardiovascular events, which favored enalapril. In ALLHAT, the treatment groups were similar in terms of the primary outcome of death from coronary causes or nonfatal myocardial infarction, but when combined with the secondary cardiovascular events, outcomes favored chlorthalidone. Perhaps comparison of the demographic and clinical characteristics of the subjects in the two trials can help. Age, sex, and body-mass index were similar. Ninety-five percent of the subjects in ANBP2 were white, whereas 35 percent of the subjects in ALLHAT were black. In ANBP2, the pretreatment blood pressures were higher. Could the differential in achieved blood pressure between the chlorthalidone group and the lisinopril group in ALLHAT have affected its results? The percentages of patients with diabetes, smokers, and patients with coronary heart disease or cerebrovascular disease in ANBP2 were lower. These characteristics could also have an effect on outcomes.4,5

In order to obtain firm answers to these questions for ourselves and our patients, medical leaders and responsible health care providers should assume more direct oversight of the interpretation of such studies. Whereas epidemiologists focus on responses at the population level in order to develop therapeutic guidelines, health care providers must deal with the specific relationship between the physician and the patient. This relationship is where the therapeutic tire meets the road, and there is no place for absolute or categorical answers. Population-based studies of therapies help to point the way but are not analogous to the care of individual patients.

Elsewhere in this issue of the Journal, there is an informative article by August6 that describes an exceedingly common clinical problem faced by all primary care physicians: the initial treatment of patients with less severe essential hypertension. Although such hypertension was formerly considered to be "mild," we must recognize that all hypertension is severe in that it is associated with an increased risk of premature illness and death. August outlines the importance of a comprehensive evaluation and the necessity for prompt recognition and treatment of hypertension.

Now we can develop specific resolutions to the apparent dilemma presented by the results of ANBP2 and ALLHAT. For patients with essential hypertension but without complications, it makes sense for the prescribing physician to choose a diuretic in a dose that does not cause potassium wasting, precipitate gout, or have other unwanted effects. In ANBP2 and ALLHAT, it was frequently necessary to prescribe a second or third medication in order to control blood pressure. In such a circumstance, the addition of an ACE inhibitor makes sense. Furthermore, a diuretic alone is not sufficient for the achievement of blood-pressure goals in some patients with hypertension, and both ACE inhibitors and diuretics are valuable and currently available as generic compounds. One should not lose sight of the fact that both diuretics and ACE inhibitors are extremely effective in improving clinical outcomes.7,8,9 However, patients with hypertension — particularly elderly patients — frequently have associated coexisting conditions. If a patient has diabetes, it would certainly be wise to initiate therapy with an ACE inhibitor, as long-term studies have clearly demonstrated.10,11,12 If a patient has cardiac failure, one might use both a diuretic and an ACE inhibitor. If there is a history of myocardial infarction, an ACE inhibitor diminishes the risks of future cardiac failure, a second infarction, and subsequent death13,14,15; a beta-blocker is also indicated for such a patient.7 If the patient has angina pectoris, whether from atherosclerotic epicardial coronary artery disease or from hypertensive arteriolar disease, it may also be wise to use a calcium antagonist. Dihydropyridine calcium antagonists not only relieve chest pain, but also help to prevent strokes.7,16

The answer to our question about what we are to believe has now become apparent. First, measure blood pressure in all patients. Second, if blood pressure remains elevated, control it with medication so as to achieve the blood-pressure goal (systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg). In selecting appropriate therapy, choose a drug or a combination of drugs for which there is strong evidence of effectiveness in persons with the type of problem found in the patient.

Finally, we must not join the clamor of media and industry, allowing newscasts to declare immediately which class of drugs is best. Treatment of the individual patient with hypertension is complicated, requiring time and judgment. In choosing between a diuretic and an ACE inhibitor, the physician can make a reasonable selection by reviewing the patient's history and course. We must remember that trials describe population averages for the purposes of developing guidelines, whereas physicians must focus on the individual patient's clinical responses.


Ibuprofen Could Be Bad for Heart Patients
Fri Feb 14, 7:31 AM ET  By EMMA ROSS, AP Medical Writer

LONDON - Fresh evidence adds to suspicions that ibuprofen could be dangerous for most heart patients because it can block the blood-thinning benefits of aspirin.
New research published this week in The Lancet medical journal found that those taking both aspirin and ibuprofen were twice as likely to die during the study period as those who were taking aspirin alone or with other types of common pain relievers.

Scientists believe ibuprofen clogs a channel inside a clotting protein that aspirin acts on. Aspirin gets stuck behind the ibuprofen and cannot get to where it is supposed to go to thin the blood.

Aspirin is considered the most important medicine for heart disease. Nearly all heart patients take it every day because it prevents the clots that cause heart attacks and strokes. Ibuprofen, which is in Motrin and Advil among other brands, is widely used for arthritis and other aches and pains.

Scientists at the Medicines Monitoring Unit of Britain's Medical Research Council checked the medical records of 7,107 heart patients who had been discharged from hospitals between 1989 and 1997 with aspirin prescriptions and had survived at least one month after leaving the hospital.

They were divided into four groups according to their prescriptions.

The first group included those on aspirin alone.

The second were given aspirin and ibuprofen and the third group had aspirin with another pain killer, diclofenac. Ibuprofen and diclofenac both belong to a widely used class of pain relievers known as nonsteroidal anti-inflammatory drugs, or NSAIDs.

The last group included those taking aspirin with any other NSAID, such as acetaminophen, which is in Tylenol.

The researchers found that those taking ibuprofen were almost twice as likely as those taking aspirin alone to die by 1997. That meant that for every 1,000 patients treated, there were 12 extra deaths a year when ibuprofen was taken with aspirin.

For heart-related deaths, ibuprofen was linked to three extra deaths per 1,000 patients treated per year.

Experts say it is important to track both heart-related deaths and deaths in general because deaths are sometimes attributed to the wrong cause and heart-related cases may be missed. For instance, a death certificate may say the person died in a car crash when, in fact, a heart attack or stroke at the wheel caused the crash.

No extra deaths were seen in the groups taking the other types of NSAIDs.

"The message here is beginning to be 'go for something other than ibuprofen,'" said Garret FitzGerald, who was not connected with the latest study, but whose research sparked concerns about the combination just over a year ago.

"Mechanistically, you have a very clear rationale for why it should happen," said FitzGerald, professor of cardiovascular medicine and chair of pharmacology at the University of Pennsylvania. "Now we have four studies each coming out with the same message. It's several pieces of ancillary evidence that when assembled are more persuasive than when taken in isolation."

"Lots of people take these two kinds of drugs chronically and probably a large number take both together chronically," FitzGerald said. "Talk to your doctor before you embark on this combination thinking that it's totally innocuous because both are available over the counter."

Dr. Tom MacDonald, who led the Lancet study, said taking the odd ibuprofen for a few days would not be a problem. It's regular use that seems to be at issue.

But the findings are not rock solid, experts said.

"This definitely raises a red flag ... but I don't think this can be viewed as the definitive answer on the question," said Dr. Veronique Roger, head of cardiovascular research at the Mayo Clinic in Rochester, Minn., who was not connected to the study.

It could be that heart patients who take ibuprofen have additional conditions that in turn make them more prone to premature death and were not accounted for in the study, she noted.

___
Baby, Coated Aspirin May Not Prevent Stroke-Study
Fri Feb 14, 5:38 PM ET  Add Health - Reuters to My Yahoo!
By Maggie Fox
WASHINGTON (Reuters) - People who take baby aspirin or coated aspirin to try to prevent heart attacks or strokes may not be getting the benefits they expect, US researchers said on Friday.

A study of more than 250 people showed that most of those who took low-dose or coated aspirin in fact saw no reduced blood clotting, the researchers told a meeting of the American Stroke Association in Phoenix.

Full-sized, uncoated aspirin seemed more effective, according to a measurement of the blood's stickiness called platelet function, said Dr. Mark Alberts, director of the Stroke Program at Northwestern Memorial Hospital in Chicago.

"More than 50% of patients who got coated or low dose aspirin seemed to have normal platelet function," Alberts said in a telephone interview. "This is remarkable."

He said his study would help explain why aspirin does not seem to work for many people. "About half the patients who have a heart attack or stroke are taking aspirin at the time they have a heart attack or stroke," he said.

Several studies have shown that aspirin can reduce blood clotting, lowering the risk of heart attack and stroke. Stroke is the third leading cause of death in the United States, affecting 750,000 people a year and killing 165,000.

But aspirin can be dangerous. It and related drugs are blamed for thousands of deaths every year, so doctors want patients to take the lowest-possible dose that is effective.

Alberts and colleagues tested 126 patients prescribed aspirin after having strokes or clogged arteries to the brain.

LOW-DOSE ASPIRIN WORK IN FEWER THAN HALF

The patients were taking various doses and formulations of aspirin. Alberts found that 56% of those taking 81 milligram "baby" aspirin had no changes in blood clotting.

But 72% of patients taking 325 mg aspirin pills had measurable effects.

He found 65% of patients taking coated aspirin--no matter what the strength--had no reduced clotting, while 75% of patients taking uncoated aspirin did have reduced clotting.

Alberts stressed that no one should be taking aspirin to prevent heart disease or stroke without first visiting a doctor. But he said his study suggests that doctors may want to take the time to check to see whether aspirin is working in a patient, perhaps using the platelet test.

The findings have implications for more than patients.

Bayer this week asked the US Food and Drug Administration (news - web sites) to allow it to market aspirin to prevent a first heart attack or stroke, and it has launched a specially packaged 81 mg coated aspirin product.

In 2002 Bayer sued rival Johnson & Johnson over Johnson's advertising for its St. Joseph brand of aspirin, which comes in a "baby" dose. Bayer argued that larger doses of aspirin were more effective than the lower doses.

Dr. Allen Heller, vice president and head of global research and development for Bayer, said he would have to study the findings further but also stressed that no one take aspirin for preventing heart disease without a doctor's advice. But he said Bayer had little guidance for doctors.

"We don't tell doctors what dose to prescribe," he said.

Aspirin is not approved for children or babies because it can cause a fatal brain condition called Reye syndrome.


PLAC test
The PLAC Test Advances Stroke and CHD Prevention
The PLAC test is the only FDA-cleared blood test to aid in determining the risk for ischemic stroke associated with atherosclerosis
Elevated Lp-PLA2 doubles an individual's risk of experiencing an ischemic stroke or coronary event, independent of traditional risk factors
Lp-PLA2 is additive to blood pressure in predicting future incident ischemic stroke
Major clinical studies have shown Lp-PLA2 to be highly predictive of cardiovascular risk
The PLAC test provides accurate, reliable results that you can trust to identify your patients who may be at an elevated risk for a future ischemic stroke or coronary event

By measuring levels of Lp-PLA2 (lipoprotein-associated phospholipase A2), a cardiovascular-specific inflammatory enzyme implicated in the formation of vulnerable, rupture-prone plaques, the PLAC test provides important information specific to your patient's risk of an ischemic stroke or coronary event.
The PLAC test is a blood test that was cleared by the FDA for the quantitative determination of Lp-PLA2 in human plasma to be used in conjunction with clinical evaluation and patient risk assessment as an aid in predicting risk for coronary heart disease, and ischemic stroke associated with atherosclerosis.
Predictive. Powerful. Specific.
Predictive
Levels of Lp-PLA2 have been found to be significantly higher in cases of ischemic stroke, while LDL-C levels typically have not
Lp-PLA2 can help identify stroke-prone hypertensive patients
Lp-PLA2 is a strong risk factor for stroke and CHD, statistically independent of traditional risk factors as well as markers of systemic inflammation, such as CRP and fibrinogen
The PLAC test provides you with a clearer picture to help determine the right risk reduction strategy that can prevent your patients from suffering an ischemic stroke or heart attack
Powerful
Individuals with elevated Lp-PLA2 levels double an individual's risk of stroke or coronary event, independent of traditional risk factors
Individuals with the highest levels of Lp-PLA2 and systolic blood pressure had a sixfold higher risk of suffering an ischemic stroke
Specific
Lp-PLA2 is a cardiovascular-specific inflammatory enzyme implicated in the formation of vulnerable, rupture-prone plaque
The PLAC test reports consistent and reliable values that do not typically fluctuate during acute systemic inflammation
Because Lp-PLA2 is not typically elevated by other concomitant inflammatory conditions, it can easily be used in all necessary patients to gather accurate cardiovascular risk information
The PLAC test is a high-complexity test as categorized under CLIA 88 and must be run in laboratories that are CLIA-certified as highly complex.


TAKING YOUR BLOOD PRESSURE AT HOME  by Mandie, Devincentis, R.N.
* The earpieces of the stethoscope should be pointing towards your noe.
* The blood pressure cuff has the word 'artery' written on it with a vertical line just below it. This is meant to help you position the cuff correctly and you should line it up so that it is just above your antecubital artery (located at the inner bend of your elbow).
* Wrap the cuff completely around your arm, between your shoulder & elbow, at the heart level. If you have another person at home this is the part where you will most likely need some assistance at first. The cuff should not be able to slip around or fall down your arm on it's own. Also, don't wrap the cuff around your arm too tightly. You should just be able to fit the head of your stethoscope underneath the cuff.
* It's easier to control the cuff inflation & deflation if you place the blood pressure cuff on your non-dominant limb. However, there is no reason why this is medically necessary. It's just easier this way.
* Before you begin inflating the cuff, make sure the air valve is closed (i.e. turn it to the right to close it). Also, make sure you can easily release the valve (by turning it to the left) with your thumb and index finger before pumping up the cuff.
* If you know (approximately) what your top number usually is, add 40 and pump up the cuff until the needle reaches around this number. Then slowly release the valve with your thumb & index finger by turning it to the left. The needle should fall steadily if done correctly.
* The FIRST beat you hear is the top number of your blood pressure. As the needle falls, the beats you hear will sound methodical & become softer. Listen closely because the LAST beat you hear is the bottom number of your blood pressure. This might take some practice.
* If you do not feel confident with your blood pressure reading after two attempts and want to try taking it again, you should either switch arms OR wait 10-15 minutes before trying again on the same arm. Taking it more than twice in a row on the same arm can increase the arterial pressure & give you an inaccurate reading.
* Never use the same side hand to inflate the cuff as the arm on which it is placed. In other words, if the cuff is placed around your left arm you don't want to pump it up with your left hand. This will give you an inaccurate reading because pumping your fist increases the arterial pressure in that arm.
* When documenting your BP reading note the time, date, & whether or not you have taken your medications. It's also a good idea to mention any changes recently made in your medications, how you are feeling (i.e. stressed, tired, relaxed, etc.) and anything else you may feel is important.
* Bring your documented blood pressure readings to your appointments. I will make a copy of them to keep in your chart.
* If you don't feel confident in your readings and would like me to show you again, just let me know and we will review it together at the office. We'll go over it as many times as you need, just ask.
Good Luck!
Mandie, R.N.

Walnuts May Decrease Risk of CVD
New York - A new study shows that walnuts can lower low-density lipoprotein (LDL) cholesterol levels and reduce cardiovascular disease (CVD) risk.
Earlier research has suggested that nuts in general provide health benefits, specifically coronary benefits. Some studies have shown that eating 5 servings of nuts per week reduced the risk of heart attacks by 40%-50%. Although there are several theories on the potential mechanisms of the protective effect of nuts, the exact mechanism is unknown.
In this study, published in the July issue of the American Journal of Clinical Nutrition, researchers looked at walnuts exclusively and found that adding walnuts to both regular and low-fat diets significantly reduced total cholesterol as well as the low-density lipoprotein (LDL) cholesterol levels. This finding, researchers say, suggests that the way walnuts lower cholesterol is by changing lipid distribution in favorable ways.
"What's different about walnuts is that they are rich in polyunsaturated fat, while other nuts are rich in monounsaturated fat," says study author Sidika Kasim-Karakas, MD, of the department of endocrinology and nutrition at the University of California at Davis. "We have identified a potential additional mechanism by which walnuts prevent heart disease."
Five men and 13 postmenopausal women (average age, 60 years) who have high cholesterol and high triglyceride levels) participated in the study. They were given 4 diets in sequence over a period of 5.5 months:
Regular (pre-study) diet.
Regular diet + walnuts.
Low-fat diet.
Low-fat diet + walnuts.
Participants were on each diet for 6 weeks. At the end of each diet, researchers measured cholesterol and triglyceride levels. "Wherever we added walnuts, regardless of [whether it was] the second or the fourth phase, we had favorable changes in the small [density] LDL," says Dr. Kasim-Karakas.
"We showed a decrease in small-density LDL from 46% in the regular diet to 33% in the regular plus walnuts diet," says Dr. Kasim-Karakas. More studies on walnuts or nuts in general are needed to understand better the mechanisms of their protective effect, he said.
John Sabaté, MD, DrPH, professor of nutrition at the School of Public Health at Loma Linda University, California, who has done extensive research on walnuts, says that his studies have shown that eating walnuts lowered cholesterol among both healthy men and women as well as people with high cholesterol.
"This study confirms our previous results that walnuts reduce lipoprotein cholesterol levels," says Sabaté. "Supplementation of walnuts lower[s] not only the total amount of cholesterol, but the LDL cholesterol, preferentially lower[ing] the small particle LDL."
But Dr. Sabaté points out that it is difficult to distinguish the precise effects of different diets because they were administered consecutively. "The results need to be repeated, especially on the small LDL," says Sabaté.
One interesting point in the study is that walnuts did not increase weight in people who consumed walnuts in addition to their regular diets, says Lola O'Rourke, MS, RD, a spokesperson for the American Diatetic Association.
"Although the mechanism is not entirely clear, one theory is that nuts are very satiating, they give a sense of satisfaction so people stop eating sooner," Ms. O'Rourke explains.
O'Rourke points out that over the last few years, fat intake has gone down, yet the number of Americans who are overweight has gone up. One reason may be that there are many low-fat and non-fat products popping up on the market, and people are probably eating more of them.
"Many people in our society are 'fat phobic,' and nuts are often perceived as something that should be avoided for that reason," says O'Rourke. "It's important to keep in mind that some fat is still a good thing. The basis of a balanced diet is variety and moderation. Nuts fit into that extremely well."
Am J Clin Nutr. 2001;73(7):000-000

Hong Mautz is senior news writer with CBS Healthwatch, Medscape's sister site for patients.
MedscapeWire is edited by Deborah Flapan, an associate editor at Medscape. Send press releases and comments to medscapewire2@medscapeinc.com.  Fruit, Vegetables Do Matter Against Heart Disease, Says Large, Long-Term Study
URL: http://www.annals.org/issues/v134n12/abs/200106190-00010.html
Ann Intern Med. 2001;134: 1106-1114. "The Effect of Fruit and Vegetable Intake on Risk for Coronary Heart Disease"
06/21/2001 08:03:46 AM
By Anne MacLennan


consumption of fruits and vegetables, particularly those rich in vitamin C and green leafy vegetables, to a protective effect against coronary heart disease
Until now, data on the relationship have been sparse, although many constituents of fruits and vegetables are known to reduce risk for coronary heart disease.

This was a prospective cohort study set within the large Nurses' Health Study and Health Professionals' Follow-up Study in the United States.

Kaumudi J Joshipura and colleagues from Harvard School of Public Health, Harvard School of Dental Medicine, Channing Laboratory, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts did the research.

Participants were 84,251 women aged 34 years to 59 years who were followed for 14 years and 42,148 men aged 40 years to 75 years who were followed for eight years.

All of the participants were free of diagnosed cardiovascular disease, cancer and diabetes at baseline.

As the main outcome measure, researchers used incidence of nonfatal myocardial infarction or fatal coronary heart disease (1,127 cases in women and 1,063 in men).

Diet was assessed by food-frequency questionnaires.

Once researchers took standard cardiovascular risk factors into account, people in the highest quintile of fruit and vegetable consumption had a relative risk for coronary heart disease of 0.80 versus those in the lowest quintile.

Indeed, each one-serving/day increase in fruit or vegetable intake was linked with a four percent lower risk for coronary heart disease.

Green leafy vegetables and vitamin C-rich fruits and vegetables contributed most significantly to the apparent protective effect of total fruit and vegetable intake.

toxic compound is formed when sugar, proteins and fat are processed at cooking temperatures for long periods of time. This compound may increase blood vessel damage in diabetics

In a study appearing this week in the Proceedings of the National Academy of Sciences (news - web sites), researchers say a toxic compound is formed when sugar, proteins and fat are processed at cooking temperatures for long periods of time. This compound may increase blood vessel damage in diabetics, the study suggests.
Dr. Helen Vlassara, a diabetes researcher at Mount Sinai School of Medicine in New York and first author of the study, said the compound, called advanced glycation end products or AGEs, can prompt an angry reaction from the immune system, eventually damaging blood vessels.
"AGEs attack virtually every part of the body," said Vlassara. "It is as if we have a low-grade infection. They tend to aggravate the immune cells."
She said a lifelong diet high in AGEs leaves the immune system in a constant state of low-grade inflammation which damages the small and mid-sized arteries. This, in turn, can prompt heart disease and other problems common to diabetics, she said. Diabetics are particularly sensitive to the effects of vessels damaged by AGEs, she said.
But dietary AGEs can be controlled by cooking foods differently, she added.
Dr. Eugene Barrett, a professor of medicine at the University of Virginia and the president-elect of the American Diabetes Association, said the study by Vlassara is potentially important in the control of diabetes, but more research is needed to understand the role AGEs may play in heart disease.
He said research into AGEs is still at an early stage and it may be too soon to conclude that limiting AGEs will reduce heart disease among diabetics.
Vlassara's study used 24 diabetic patients divided into two groups. One group maintained a normal diet recommended for diabetics which included chicken, fish and meat. The other group had the same foods, but cooked differently.
At the end of six weeks, said Vlassara, the AGEs in the test group registered declines ranging from 33 percent to 40 percent. She said the study was too short to detect any fundamental changes in the patients' health.
However, she said studies using diabetic animals have shown that a reduction in AGEs can reduce the incidence of heart disease or delay its onset. Such studies need to be conducted in humans to prove the value of AGE control, she said.
The key to lowering AGEs, said Vlassara, is to cook for a short time in the presence of high humidity. This means either boiling or steaming meats for the minimum time required. Meat can be sauteed, she said, but it should be cut very thin and cooked quickly with a small amount of oil.
She said one of the worst AGE offenders is turkey cooked in the traditional American way.
"We cook for many hours," she said. "That would tend to make a tremendous number of AGEs."
Vlassara said coffee, cola and chocolate drinks also are loaded with AGEs. For diabetics, she recommends sugar-free versions of clear sodas instead of the diet versions of dark drinks. Some of the dark colas, she said, add caramelized products which are heavy in AGEs. MRI Artery Scans Predict Stroke Risk-Studies
Mon Jun 9, 5:30 PM ET  Add Health - Reuters to My Yahoo!
By Ransdell Pierson

MRI PREDICTS STROKES

NEW YORK (Reuters) - Magnetic resonance imaging can help predict which patients are at risk of strokes from clogged arteries, and thereby alert patients to have surgery or take protective drugs, according to two studies released on Monday.

The studies involving the carotid artery, appearing in Circulation: Journal of the American Heart Association (news - web sites), were the first to use MRI scans to detect bleeding within fatty plaque material that lines and clogs arteries.

Such bleeding indicates the plaque has become "complicated," meaning the surface of the deposit has broken apart and pieces of it could travel to the brain, forming clots that cause stroke.

Strokes often occur when branches of the carotid artery, the main blood vessel supplying blood from the neck to the brain, become clogged and brain cells become starved of blood and oxygen.

MRI scans used in the two studies detected high-risk complicated plaque in the carotid arteries of 60 percent of patients who had shown signs and symptoms that precede stroke -- including "mini-strokes" which cause no major permanent damage but indicate danger of serious future strokes.

By contrast, MRI scans found no complicated plaque in the carotid arteries of a smaller group of people who had no previous signs or symptoms of stroke.

One of the studies involved 63 patients who had surgery to remove obstructions in the carotid artery.

Fatty deposits removed during the surgeries were later analyzed by conventional pathology techniques and showed complicated plaque in 44 patients.

MRI scans taken before surgery successfully predicted complicated plaque in 41 of the patients, an accuracy rate of 93 percent.


"The MRI studies show that plaque is not some benign quiet process in which the arteries gradually harden," said Dr. Alan Moody, who helped write the two Circulation reports.


"In up to 60 percent of cases, active bleeding is going on within the plaque -- making the plaque bigger and further clogging the artery," said Moody, who is chief radiologist at Sunnybrook and Women's College Health Sciences Center in Toronto.

He said all patients with such bleeding are at elevated risk of stroke and that many could benefit from surgery or certain drugs that help keep plaque from breaking up into dangerous pieces. They include statins, a popular class of cholesterol-lowering medicines.

Angiography is currently the "gold standard" for verifying plaque in arteries. But Moody said the procedure, which involves running a catheter between the patient's groin and neck and then filling it with dye, actually causes strokes in 1 percent of patients.

He said other screening procedures -- including ultrasound, computed tomography and positron emission tomography -- can also indicate the presence of plaque but without the convenience and detailed information available from MRI scans.

"In the future, the new gold standard of identification may be a combination of ultrasound and MRI scans," Moody said, adding that other studies suggest combined use of those non-invasive tests may provide the same detailed level of information as angiography.

Moody said angiography procedures currently cost about $1,000, compared with $250 for ultrasound and $400 for MRI scans.

The Circulation articles said MRI scans might also hold promise in detecting elevated risk of heart attack in patients with complicated plaque.




Raising HDL levels may be as important as lowering LDL
Researchers find that changing the focus of lipid-lowering therapy may improve outcomes, but some experts say it is too soon to alter recommendations.
By Victoria Stagg Elliott, AMNews staff. April 28, 2003.

Targeting drug therapy to raise levels of HDL cholesterol alone may be sufficient to reduce the risk of heart disease and improve cardiovascular health, according to several studies presented at the American College of Cardiology meeting held earlier this month in Chicago.
One study, which was presented by researchers at the Heart Institute, Sheba Medical Center in Tel Hashomer, Israel, found that raising HDL cholesterol was associated with improved long-term survival among more than 1,500 patients with coronary disease.
Another from the Uniformed Services University of Health Sciences in Bethesda, Md., randomized nearly 150 patients with stable coronary disease to receive either medications to raise HDL or a placebo. Those on meds increased their HDL as well as decreasing their total cholesterol significantly and had far fewer heart-related mortality or morbidity events.
"There's ample epidemiologic evidence that HDL cholesterol is very predictive of cardiovascular events," said Maj. Richard A. Krasuski, MD, the study's lead author and director of cardiovascular research at Uniformed Services University. "This study suggests that it could be possible that aiming to raise the HDL may be as good or maybe even better than trying to lower the LDL."
Although these studies focused on people who have already had cardiac events, the strategy does have the potential to impact prevention for those who do not yet have heart disease. "If you have a primary prevention group that has a number of cardiovascular risk factors and a low level of HDL cholesterol, I think looking at ways to raise HDL is certainly a viable option, but it's certainly one that needs further study," said Dr. Krasuski.
Low HDLlevels have long been acknowledged as a heart disease risk factor. Last November's guidelines, the most recent, from the National Institutes of Health's National Cholesterol Education Project, "Detection, Evaluation and Treatment of High Blood Cholesterol in Adults," raised the bar by increasing the definition of low HDL to less than 40 mg/dl from less than 35 mg/dl.
Traditional treatment goals have always been to lower the total cholesterol as well as levels of LDL, and the new guidelines did not suggest an HDL goal. "In all persons with low HDL cholesterol, the primary target of therapy is LDL cholesterol," spelled out the guidelines.
But increasingly, experts are recognizing HDL as an independent risk factor that needs to be addressed. "The epidemiology is strong, and the population data are compelling," said Andrew Tonkin, MD, head of cardiovascular disease epidemiology and prevention at Monash University in Melbourne, Australia.
Experts said, though, that more data were needed before clinical practice should be altered. Head-to-head trials pitting drugs that primarily lower LDL against ones that are most effective at raising HDL are needed.
"I'm kind of a [National Cholesterol Education Program] guideline person, and they were the biggest on the LDL," said Paul Thompson, MD, director of preventive cardiology at Hartford Hospital in Hartford, Conn. "We have less outcome data on raising the HDL than we do on lowering the LDL, and we need outcome data."
No escaping lifestyle changes
The conference was not solely focused on the role of various drug therapies. Experts were quick to point out that lifestyle changes can be just as effective or even more so at improving a patient's cardiac risk profile, either by themselves or with medications. Several studies were presented highlighting that drastic lifestyle alterations can improve heart health.
One study from Indiana University School of Medicine in Indianapolis suggested that exercise could increase the number of vessel wall repair cells circulating in the blood. Another from the University of Texas Medical School at Houston suggested that exercise as well as extreme dietary changes accompanied by traditional lipid-lowering medications may offer advantages over medication with only minor lifestyle changes.
In the UT study, more than 400 patients with coronary artery disease were randomized to receive either no intervention; an intervention involving an extremely low-fat diet combined with exercise and medication; or an intervention combining minor lifestyle changes and traditional drug therapies. The group that exercised and ate an extremely low-fat diet had a cardiac event rate of just over 6%. Those who made only minor changes had a rate of around 20%. Those who did nothing had a rate of 30%.
"Pills don't substitute for diet and exercise," said Stefano Sdringola, MD, lead author and assistant professor of cardiology at the University of Texas Medical School, Houston.


For primary prevention of stroke, adequate blood pressure reduction, and treatment of hyperlipidemia, use of antithrombotic therapy in patients with atrial fibrillation and of antiplatelet therapy in patients with myocardial infarction are effective and supported by evidence from several randomized trials. Effective strategies for the secondary prevention of stroke include treatment of hypertension and hyperlipidemia, antithrombotic therapy for patients with atrial fibrillation, antiplatelet therapy, and carotid endarterectomy in patients with severe carotid artery stenosis.
Conclusions Stroke is a major public health concern, and a significant body of evidence supports many primary and secondary prevention strategies.
JAMA. 2002;288:1388-1395


PLAVIX Cuts Risk of Second Stroke, Heart Attack
WEDNESDAY, Nov. 12 (HealthDayNews) -- The anti-clotting medicine clopidogrel reduces the risk of recurrent heart attack and stroke and is cost-effective.That's the conclusion of an Emory University study presented Nov. 12 at the American Heart Association (news - web sites)'s annual conference in Orlando, Fla."We have three separate investigations showing uniform results in both the short- and long-term use of clopidogrel. Specifically, the use of clopidogrel in addition to aspirin produces a significant risk reduction in recurrent heart attack, stroke or cardiovascular death," Dr. William Weintraub, a researcher at the Emory Center for Outcomes Research, says in a prepared statement.



Soy Helps Even with Normal Cholesterol
Updated 6:08 PM ET March 2, 2001
WASHINGTON (Reuters) - Even people with normal levels of cholesterol can benefit from eating more soy because it boosts levels of so-called good cholesterol, researchers said on Friday.
Heart experts said the study supports their advice that Americans replace at least some artery-clogging meat and dairy foods with soy protein.
Healthy people who ate food with extra soy protein, such as baked items made with soy flour, saw their high density lipoprotein (HDL or good) cholesterol go up while levels of low density lipoprotein (LDL or bad) cholesterol stayed down.
"Our study demonstrates that, in a population with normal cholesterol levels and low dietary protein intake, soy protein increases HDL in the bloodstream, but does not significantly alter LDL," Dr. Jiang He of Tulane University School of Public Health and Tropical Medicine in New Orleans, who led the study, said in a statement.
He, who presented his team's findings to a meeting of the American Heart Association in San Antonio, tested 60 men and 90 women in China, aged 35-65, all of whom had normal cholesterol levels.
"People in China usually consume a low-protein diet and get little animal protein," He said. This makes them less likely to develop high cholesterol and heart disease in the first place.
He's team fed half of them biscuits containing soy protein supplements every day, and half were given a different biscuit.
Three months later, those who ate the soy showed on average a 4.7 percent increase in HDL, which carries artery-clogging fat out of the blood vessels for disposal.
The American Heart Association last year recommended that everyone eat more soy, and said this study supports its position. Several studies have shown that adding soy protein to the diet can help people lower high cholesterol -- especially if it replaces meat and cheese.
"There is increasing evidence that consumption of soy protein in place of animal protein lowers blood cholesterol levels and may provide other cardiovascular benefits," the association's Nutrition Committee said in a statement.
"Most bean proteins are good for health," He said. "However, soybean protein is the only one that has been documented to affect cholesterol levels by clinical trials conducted in western countries."
Most Americans get more protein than they need anyway. Human beings need to get only 15 percent of calories from protein. But soy is considered a "complete" protein that has all of the nutritional benefits of meat.



Crestor Drug Beats Lipitor in Study  Mon Sep 6, 6:56 AM ET
  LONDON (Reuters) - AstraZeneca Plc's cholesterol-lowering drug Crestor performed better than Pfizer Inc's Lipitor (news - web sites) in an AstraZeneca-funded study of patients with metabolic syndrome, according to results released on Monday.

Metabolic syndrome covers a cluster of risk factors that predispose people to diabetes and heart disease, including obesity, high blood pressure, high blood sugar, high blood fat levels and low levels of beneficial HDL cholesterol.

Nearly a quarter of adults in the West have the condition.

The 400-patient clinical trial found that patients with metabolic syndrome given 20 milligrams a day of Crestor had a 49 percent reduction in levels of harmful LDL cholesterol levels after 12 weeks of treatment while their HDL increased 10.5 percent. Those on the same dose of Lipitor had a 43 percent decline in LDL and only a 5.7 percent increase in HDL, according to findings presented at the annual meeting of the European Association for the Study of Diabetes in Munich.

"Results from this study show that Crestor is an effective medication for this higher-risk patient group," said Dr Christie Ballantyne of Baylor College of Medicine in Houston, one of the study investigators.

AstraZeneca, which launched Crestor last year, is battling for market share against Lipitor, which with annual sales running at some $10 billion dominates the lucrative cholesterol drug market.

Cholesterol medicines are the biggest sellers in the world, with aggregate sales totaling $24.7 billion in the 12 months to June, according to healthcare consultancy IMS Health.

AstraZeneca's Crestor has so far taken only a small part of that market, with sales in the second quarter of 2004 totaling $207 million, but the Anglo-Swedish firm is aiming to secure a 20 percent share.

Part of its strategy involves conducting a large number of post-launch clinical studies, which are designed to prove the effectiveness of Crestor and lay to rest concerns about possible adverse side effects.

The latest study is part of much larger project. So far, three studies in the so-called Galaxy clinical trials program have been completed and 14 studies are ongoing, which have in total recruited more than 40,000 patients.

AstraZeneca said the latest study, known as Comets, showed Crestor to be well tolerated, with a rate of adverse events similar to that seen with Lipitor.Omega-3 Fatty Acids Improve Systemic Arterial Compliance
Laurie Barclay, MD
Medscape Medical News 2002. © 2002 Medscape


OMEGA THREE IMPROVES ARTERIAL COMPLIANCE Two omega-3 fatty acids contained in fish, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), significantly improve systemic arterial compliance, according to the results of a double-blind, placebo-controlled trial reported in the August issue of the American Journal of Clinical Nutrition. As a result, systolic and pulse pressure and total vascular resistance tended to decrease, while triglyceride levels dropped significantly.
"Substantial epidemiologic and other evidence shows that eating fish may benefit people at high risk for ischemic heart disease (IHD), [and] sudden cardiac deaths occur less frequently in individuals who habitually [eat] fish," write Paul Nestel, from Baker Medical Research Institute in Melbourne, Australia, and colleagues. "Because of increasing evidence linking heightened pulse pressure, a reflection of increased arterial stiffness, to increased coronary risk, interventions that improve arterial compliance are thought likely to reduce risk for IHD."
During a seven-week dietary intervention, 38 middle-aged men and women with elevated plasma total cholesterol were randomized to treatment with an EPA supplement (3 g/day), a DHA supplement (3 g/day), or placebo.
Systemic arterial compliance was unchanged in the placebo group, rose 36% in the EPA group and 27% in the DHA group (P=.043), and there was a trend toward reduced systolic and pulse pressure in the omega-3 fatty acid groups. Plasma total and very low density lipoprotein triacylglycerol concentrations were significantly lower in the treatment groups than in the placebo group (P=.026 and .006, respectively).
"EPA and DHA increase systemic arterial compliance and tend to reduce pulse pressure and total vascular resistance, effects that may reduce the risk of adverse cardiovascular events," the authors write.
Am J Clin Nutr. 2002;76:326-330
Reviewed by Gary D. Vogin, MD
Laurie Barclay, MD, is a staff writer with WebMD.
Medscape Medical News is edited by Deborah Flapan, an associate editor at




Coronary Magnetic Resonance Angiography for the Detection of Coronary Stenoses

W. Yong Kim, M.D., Ph.D., Peter G. Danias, M.D., Ph.D., Matthias Stuber, Ph.D., Scott D. Flamm, M.D., Sven Plein, M.D., Eike Nagel, M.D., Susan E. Langerak, M.Sc., Oliver M. Weber, Ph.D., Erik M. Pedersen, M.D., Ph.D., Matthias Schmidt, M.D., René M. Botnar, Ph.D., and Warren J. Manning, M.D.
ABSTRACT

Background An accurate, noninvasive technique for the diagnosis of coronary disease would be an important advance. We investigated the accuracy of coronary magnetic resonance angiography among patients with suspected coronary disease in a prospective, multicenter study.

Methods Coronary magnetic resonance angiography was performed during free breathing in 109 patients before elective x-ray coronary angiography, and the results of the two diagnostic procedures were compared.

Results A total of 636 of 759 proximal and middle segments of coronary arteries (84 percent) were interpretable on magnetic resonance angiography. In these segments, 78 (83 percent) of 94 clinically significant lesions (those with a 50 percent reduction in diameter on x-ray angiography) were also detected by magnetic resonance angiography. Overall, coronary magnetic resonance angiography had an accuracy of 72 percent (95 percent confidence interval, 63 to 81 percent) in diagnosing coronary artery disease. The sensitivity, specificity, and accuracy for patients with disease of the left main coronary artery or three-vessel disease were 100 percent (95 percent confidence interval, 97 to 100 percent), 85 percent (95 percent confidence interval, 78 to 92 percent), and 87 percent (95 percent confidence interval, 81 to 93 percent), respectively. The negative predictive values for any coronary artery disease and for left main artery or three-vessel disease were 81 percent (95 percent confidence interval, 73 to 89 percent) and 100 percent (95 percent confidence interval, 97 to 100 percent), respectively.

Conclusions Among patients referred for their first x-ray coronary angiogram, three-dimensional coronary magnetic resonance angiography allows for the accurate detection of coronary artery disease of the proximal and middle segments. This noninvasive approach reliably identifies (or rules out) left main coronary artery or three-vessel disease.


Blood Pressure Drugs Fend Off Stroke
A combination of blood pressure medication and diuretics could be
a lifesaver for stroke patients. A study presented at the
European Society of Hypertension meeting in Milan finds that this
drug combination may halve a patient's risk of having a second
stroke, The Associated Press reports. In the study, 6,100 stroke
patients worldwide were given a combination of the ACE inhibitor
Aceon and the diuretic Lozol or else dummy pills for a period of
four years. The results: 150 of the patients taking the drug
combination had a stroke, compared to 255 of the patients taking
the placebo. The drug combination lowered risk even in patients
who'd had normal blood pressure, the AP says. The patients
taking Aceon and Lozol also had lower risk of complications such
as heart attack or dementia, the AP says. The question that
remains is whether it is the lower blood pressure or some other
effect of the drugs that provides the benefit. The study was
partly funded by the French pharmaceutical company Servier, which
manufactures Aceon.















 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROTECT YOURSELF
ASPIRIN
EXERCISE
HIGH BLOOD PRESSURE
WARNING TESTS
RISK
FOODS
STROKE
C-REACTIVE PROTEIN
STATINS
TESTS:
MEDICATIONS:
FATS

FRAMINGHAM HEART STUDY: THE BEAT GOES ON
HEART DISEASE: A WOMAN'S BIGGEST HEALTH THREAT
SYNDROME X
HEART BYPASS
NEW ENGLAND JOURNAL ARTICLE
Half of all myocardial infarctions occur in persons in whom plasma lipid levels are normal













 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Framingham Heart Study: The beat goes on
A long-running Massachusetts study on heart disease has dramatically changed the way medicine is practiced today, and it promises to continue to break new ground.
By Susan J. Landers, AMNews staff. Feb. 18, 2002.

In 1948 President Harry S. Truman won an upset victory over Thomas Dewey, Mahatma Gandhi was assassinated, the average income was less than $3,000 a year, life expectancy was 63 years and great numbers of people were dying of cardiovascular disease.
Also in that year, the Framingham Heart Study was begun in an attempt to identify factors that contributed to this growing epidemic of heart disease.
Intended as a 20-year study, it's still going strong. After 53 years it is the longest running prospective epidemiologic study of heart disease ever and researchers are now enrolling the grandchildren of the study's original participants.
Its success is legendary among heart specialists, boosting the fame of the town of Framingham, Mass., and even making its participants somewhat celebrities.
There's no doubt that the study's findings have been important. "The Framingham Heart Study provided the foundation for preventive cardiology as we know it today," said Roger Blumenthal, MD, director of preventive cardiology at Johns Hopkins Hospital in Baltimore.
"It was one of the first to alert doctors and the public that there are major risk factors for heart disease that we now take for granted. But 50 years ago there was still a lot of controversy about what caused heart attacks and strokes," said Dr. Blumenthal, who is also a national spokesperson for the American Heart Assn.
"We've had an enormous impact using data from the Framingham Heart Study to identify people who are at risk and then modifying those risk factors," said Teri Manolio, MD, PhD, director of epidemiology and biometry at the National Institutes of Health National Heart Lung and Blood Institute.
"We've seen heart disease death rates come down dramatically and a lot of that is due to this study," she said.
When the study began, people knew very little about heart disease, much less about its causes and virtually nothing about what could be done to prevent it, said its current director, cardiologist Daniel Levy, MD.
But through the vision of its first director, Thomas Dawber, MD, the Framingham Heart Study was the first to apply the discipline of epidemiology to a chronic, noninfectious disease.
Previously, epidemiology had mostly to do with tracking such diseases as tuberculosis, syphilis, malaria and polio, said Philip Wolf, MD, principal investigator in the Framingham study and a professor of neurology at Boston University.
"The idea that you could use the methods of epidemiology to study chronic disease evolved after World War II, and that's when the Framingham study was conceived," Dr. Wolf said.
Risk factors identified
The assumption was that heart disease would develop in some of the subjects during the study's run. It did.
Researchers were provided the opportunity to closely examine the lifestyles of the participants. And from that examination, the term "risk factor" emerged. "This is really the first time the term was used in the history of the world," Dr. Wolf said.
Researchers found that it was possible from an initial examination to determine which people were at the highest risk of developing heart disease: namely, smokers with high blood pressure and high cholesterol levels.
Previously, physicians saw patients who had already had a stroke or heart attack, said Dr. Wolf, and questions about a patient's lifestyle were answered after the fact. With this study, measurements were made before the illness occurred, he said, allowing researchers to make an unbiased assessment and have a whole group with which to compare.
The discovery of risk factors is not the only finding the study revealed. It has produced more than 1,000 scientific papers and has branched out into other areas.
There have been a number of projects related to the study of arthritis and osteoporosis, noted Dr. Levy. Additional projects underway are related to hearing loss and eye diseases as well as dementia, he added.
The project was funded and run exclusively by the NHLBI until 1971 when Boston University became the principal subcontractor for the study, Dr. Levy said.
The researchers worked with a pool of 5,209 men and women between the ages of 30 and 62 recruited from Framingham, a small town about 20 miles west of Boston. This town was chosen from among several others because it had a successful track record with community projects and its near-Boston location provided proximity to a number of prominent medical researchers, Dr. Levy said.
The study has produced more than 1,000 scientific papers.
Framingham was also fairly isolated in 1948, before construction of the nearby Massachusetts Turnpike.
Since its inception, participants have undergone extensive physical examinations and lifestyle interviews every two to four years.
Many of the original participants have returned for biennial exams for 26 years. For any particular exam at least 85% of the participants return, said Dr. Wolf. The youngest participant in the original cohort is now 84, several are older than 100 and some of the exams are carried out in nursing homes or assisted living facilities, Dr. Wolf said.
"But many still come in," he said. "We had about 300 of the original group turn up for an MRI of their brain."
Meanwhile, the study has also grown from this base. For instance, in 1971, the study recruited 5,124 children and their spouses of the original participants for a second study, called the "Offspring Study."
In 1995, researchers began recruiting from Framingham's growing minority community, the result of an influx of immigrants from Brazil, India and Pakistan. With this effort, known as the Omni study, researchers are investigating whether the risk factors associated with heart disease in these minority populations are the same as risk factors found in the other cohorts.
And last year, researchers mailed about 5,200 cards to the third generation of the original participants. The plan is to recruit about 3,500 grandchildren and their spouses.
By late December, 3,000 or so cards had been returned and about 95% said, "Sure, sign me up," Dr. Wolf said.
Loyal participants
The trust that has built between researchers and subjects is what keeps participants returning for follow-up exams, said Dr. Levy. "It's a mutual relationship," he said.
Study participants return for a variety of reasons, he noted. "Some are motivated by altruism, and some found it an opportunity for a free exam."
No one had health insurance in 1948, he remarked, and for some of the participants the prospect of a free exam was probably enough of an enticement.
As results came in, participants began to understand the importance of the study, a fact that reinforced their resolve to continue.
While the original participants may have thought their volunteerism could, some day, help their own children, little did they know that their children and grandchildren would also become participants in the study.
Thomas Berardi is one of the third-generation participants recently recruited for the study. His mother, described by Berardi as "a worrier," urged her son to take advantage of the opportunity. She was concerned that he wasn't attending to his health as he should be, Berardi said.
With a family history of heart disease -- a grandmother died at about age 70 of a sudden heart attack, a grandfather died of heart disease and his father has had some heart problems -- Berardi, at 49, admits that self-interest is partially responsible for his participation.
"By volunteering, I am going to get the checkups that I may have put off," he said.
But he acknowledges a feeling of pride in the role he and his family have played in helping many people lead longer and healthier lives.
Berardi has a cousin who lives in Florida and is also a study participant. His cousin, who receives his checkups during return visits for family reunions, noted that his Florida physician treated him like a celebrity when he revealed his involvement in the Framingham study.
Poised for the future
Crucial to the study's longevity has been its ability to move with the times and adopt the latest in technology.
When research began, blood pressure, electrocardiogram, medical history and physical exams were the tools employed. Those measures are still used today, Dr. Wolf said. "We try to make the same measurements in 2001 that we used in 1951," he said, "so we can look at changes over time."
But technology marches on. Now researchers have added echocardiography, carotid artery ultrasound and densitometry to their measures.
One important sign that researchers are keeping abreast with modern science is their new focus on genetics. They have much material to work with given the study's multigenerational nature.
"The expansion to a third generation opens up the chance to explore important new questions about disease risk, especially those related to genetics," said NHLBI Director Claude Lenfant, MD.
The researchers have been collecting DNA for about 15 years and developing cell lines for about five years, Dr. Levy said. Thousands of genetic tests will be able to be performed on a single tube of blood, he noted. "We're hoping that with this unique family structure in Framingham and the long-term nature of the data collection here, we will be able to contribute in important ways to understanding the genetic basis for common conditions that are involved in heart disease and stroke."
Participation of the third generation of subjects is also expected to further scientists' understanding of the role of genetics in the development and progression of such diseases as stroke, dementia, osteoarthritis, vision and hearing loss, Dr. Wolf said.
"We'll be able to look at all sorts of things, such as the genetic and environmental characteristics of healthy aging," Dr. Levy pointed out. Framingham researchers are working to identify a region of the human genome that appears to contain a gene that protects individuals from developing heart disease. The gene in this region is related to the production of increased amounts of high density lipoprotein, the "good cholesterol."
Researchers are also looking for locations of genes that increase the risk for heart disease and are focusing on a region containing a gene that appears to cause high levels of low density lipoprotein, the "bad cholesterol."
It is doubtful that there will be an end to the diseases studied by the Framingham Heart Study anytime soon. So does that mean the study will go on forever?
There are no guarantees. The study has to sing for its supper every five, six or seven years, and justify why it should continue, Dr. Manolio said. But it has been very successful in doing so, she added, explaining that the NHLBI soon will be announcing another six- or seven-year extension for the study.
"All I can say is that we are here today because of a track record of productivity and not just that we were productive, but the lessons learned from Framingham in many ways changed the way medicine is practiced in the United States," Dr. Levy said.
Back to top.


Study directors brought a variety of expertise
The Framingham Heart Study has had four directors in its more than 50-year life span. Daniel Levy, MD, the current director, is a clinical cardiologist. He is expanding the study to include the third generation of participants and, in doing so, is refocusing research on the family patterns of disease.
But each of those who came before him left important footprints in the direction the study took and the findings that resulted.
Thomas Dawber, MD, the director from 1949 to 1966, was the architect of the initial project. "He made it happen," Dr. Levy said. Dr. Dawber recruited participants and instituted scientific rigor in the field of epidemiology, which was a fledgling field in medicine.
After him came William Kannel, MD, who directed the study from 1966 to 1979. He was an "amazingly productive researcher," according to Dr. Levy, and the first to take the notion of risk factors and develop it fully. Dr. Kannel was probably the key scientist in the history of the study.
From 1979 to 1995, William Castelli, MD, took the helm. Dr. Levy considers him the ambassador. He got out on the lecture circuit and, with an "evangelical-like fervor," stressed the role of cholesterol as a critical risk factor for heart disease before others joined the fight.

Framingham Heart Study (http://www.framingham.com/heart/)
 
Heart Disease: A Woman's Biggest Health Threat
When it comes to heart disease, what women don't know can kill them.

For instance, most women don't realize that heart disease is a bigger threat than any other illness they might face. A recent American Heart Association (news - web sites) survey found that a majority of women thought breast cancer (news - web sites) was the leading cause of death.

"One in 28 women will die of breast cancer, whereas almost one in two will die of heart disease," says Dr. Robert Bonow, president of the heart association and chief of cardiology at Northwestern University in Chicago.

"Partly, it's that women are less aware of their risk factors. They are less likely to see heart disease as an illness that will kill them rather than men," Bonow adds.

In 2000, cardiovascular diseases claimed the lives of 505,661 American women. In the same year, 440,175 men died from these diseases, which range from heart attack to atherosclerosis, a buildup of plaque in the arteries.

With those disturbing statistics as a backdrop, February has been designated American Heart Month. And the American Heart Association (AHA) is working to spread the word that preventive measures and early screening of risk factors can help Americans thwart heart disease before it strikes.

"If we're really going to change this epidemic, it's going to take prevention. People need to know their blood pressure and cholesterol, and they need to be treated effectively," Bonow says.

"Also, people need to be more careful about their diet," he adds. "Our younger population is becoming more obese. And fewer schools are providing physical education."

To underscore the heightened risk facing women, consider these statistics: In 1980, 4 percent more American men died of cardiovascular disease than women. But by 1984, that gap had disappeared.

Today, 15 percent more women than men die of heart disease.

"These diseases claim the lives of more than half a million females every year -- about a death a minute. That's more lives than the next seven causes of death combined," states the American Heart Association.

Part of the problem can be traced to a historical lack of attention on women's health issues. While much research has been done on heart disease in men, it's only in the last decade that researchers have focused studies on women, says Dr. Nieca Goldberg, chief of the Women's Heart Program at Lenox Hill Hospital in New York City.

"I remember in medical school, when instructors referred to heart disease, they would show slides of a middle-aged businessman clutching his chest," says Goldberg, who wrote the book, "Women are Not Small Men: Lifesaving strategies for preventing and healing heart disease in women."

Another point for women to consider is that women and men get heart disease at different points in the lives. For men, it generally shows up in their 40s, but for women it usually doesn't appear until after menopause, around 60. And as the population ages, a growing number of women are being diagnosed with heart disease, Goldberg says.

What's more, men survive heart attacks more often than women. This is partly due to medical improvements in fighting heart attacks, but also because men are generally younger when they are stricken, Bonow says.

And the warning signs for heart attack differ between the sexes. Instead of the characteristic chest pain men get, women often have shortness of breath, exhaustion and discomfort in the lower chest, which can be mistaken for stomach illness. As a result, they frequently don't realize they are having a heart attack, Goldberg says.

"They need to be aware that the earlier they get to the hospital, the more likely we can save them," she says.

To prevent heart disease, women and men must address the three largest risk behaviors -- being overweight, lack of physical activity, and smoking.

Exercise and a diet rich in fruits, vegetables, grains and fish are essential. But so is early screening for high cholesterol and blood pressure. The sooner doctors can detect the warning signs of heart disease in a person, the more likely they can prevent it, experts say.

As part of American Heart Month, the AHA is also stressing the value of CPR training, which can save a heart attack victim's life. The group is also pushing an initiative to increase the number of portable defibrillators in public places.

"Heart disease is not just a U.S. issue. It's also an international issue," Bonow says. "You start with public awareness."


Time of Day Affects Drug's Blood Pressure Control
By Keith Mulvihill

NEW YORK (Reuters Health) - Several different classes of drugs can be used to get blood pressure under control, and now a small study suggests that some may be more effective at certain times of the day than others.

"Different classes of drugs act more effectively at different times of the day," Dr. Trefor O. Morgan told Reuters Health. "This differential effect has not previously been clearly shown."

The new findings suggest that prescribing more than one blood pressure medication may provide more effective treatment, according to Morgan, of the University of Melbourne in Australia.

Normally, a person's blood pressure dips and climbs over a 24-hour period. Blood pressure climbs most rapidly in the morning after awakening and typically plateaus during the middle-to-late portion of the day. It then declines in the evening and is lowest during sleep.

In the current investigation, Morgan and co-author Adrianne Anderson looked at the effects of four different blood pressure medications on 24 people over age 65 with elevated systolic blood pressure--the first number in a blood pressure reading.

Each of the patients took one medication or a placebo for two months before switching to the next treatment. Blood pressure measurements were taken three times over a 24-hour period at the end of each of five treatment periods.

The medications evaluated include a diuretic (hydrochlorothiazide), a beta-blocker (atenolol), an angiotensin converting enzyme (ACE) inhibitor (perindopril), and a calcium channel blocker (felodipine).

Their results are published in the January issue of the American Journal of Hypertension.

The investigation found that diuretics and calcium channel blockers were relatively consistent at lowering blood pressure around the clock, said Morgan. Beta-blockers, on the other hand, lowered daytime blood pressure but had little effect on nighttime blood pressure. ACE inhibitors lowered blood pressure more at night than during the day, Morgan noted.

"Experiments in animals and human observations indicate that nighttime blood pressure elevation is associated with more cardiac enlargement and a higher morbidity and mortality," Morgan told Reuters Health.

As a result, combinations of drugs may need to be used to obtain optimal blood pressure control over a 24-hour interval, according to Morgan.

"The reason that beta blockers may not have as good results as diuretics on complications may result from (its) failure of blood pressure control at night," Morgan added.

Currently, the majority of patients with hypertension are on one drug, Morgan said. However, single drug therapy controls blood pressure in less than 30% of patients, according to the Australian researcher.

"This may explain why control of blood pressure achieved in the community is so poor," he concluded.

SOURCE: American Journal of Hypertension 2003;16:46-50.

In conclusion, blood pressure is controlled by a large number of variables.We recognize this by the individual variation that occurs in response to specific drugs.The evidence from this study those different times of the day may require us to rethink our therapeutic strategies.It is probably an additional reason to use multiple drugs rather than relying on high dose monotherapy



UC Davis Study Identifies C-Reactive Protein as Cause of Blood Clot Formation
Source: University of California, Davis - Medical Center
Further underscoring the limitations of cholesterol screening in assessing a patient's risk for heart disease, a new study by UC Davis physicians is the first to conclusively link C-reactive proteins (CRP) to formation of blood clots, a major cause of heart attacks, strokes and other vascular disease. Until now, CRP had been recognized mainly as a risk marker of heart disease. The study appears in the January 25, 2003, print edition of the journal Circulation, a publication of the American Heart Association (news - web sites), and is available on the Web at www.circulationaha.org.

"The study provides further conclusive evidence that CRP, until now viewed as an 'innocent bystander' in the formation of heart disease, is in fact a key culprit that causes inflammation in the arteries, resulting in formation of clots and plaque that lead to heart attacks and strokes," said Ishwarlal Jialal, professor of pathology and director of the Laboratory for Atherosclerosis and Metabolic Research at UC Davis School of Medicine and Medical Center.

The study demonstrates that CRP causes cells in the arteries, known as human aortic endothelial cells, to produce higher levels of an enzyme that inhibits the breakdown of clots. The enzyme, plasminogen activator inhibitor-1 (PAI-1) is also a strong risk marker for heart disease, especially in diabetics (news - web sites). The study used a variety of techniques to convincingly show how CRP activates PAI-1 in aortic cells, causing lesions in the arteries that ultimately lead to formation of plaque and blood clots.

The study underscores the need to use CRP screening to more accurately assess at-risk populations, according to Jialal, who is the Robert E. Stowell Endowed Chair in Experimental Pathology.

"Based on these findings, if a patient has normal cholesterol but high levels of CRP, an aggressive course of treatment is recommended to help the patient reduce the risk of heart attack, stroke and other heart diseases," said Jialal. "By relying on cholesterol alone, a physician could significantly underestimate a patient's risk level."

High CRP levels can occur in otherwise healthy individuals, according to the study. Patients with high levels of CRP can reduce risk by losing weight, exercising on a regular basis, stopping cigarette smoking, or taking statin drugs, Jialal added.

The study also closely links CRP and PAI-1 to diabetes and metabolic syndrome, a disorder characterized by a disproportionate amount of abdominal fat, elevated blood pressure, blood sugar and triglycerides and low levels of HDL, the "good" kind of cholesterol.

"In another important discovery, this study shows that in the presence of high blood-glucose levels, CRP is especially active in the stimulation of PAI-1. As a result, the effect of CRP is especially acute for patients with diabetes and metabolic syndrome," said Sridevi Devaraj, a co-investigator and assistant professor of pathology at UC Davis. "Given the current pandemic of obesity which increases one's risk of diabetes, the study's insights about the active role of CRP and PAI-1 in heart disease are especially valuable."

The new study adds to the findings of another landmark study on CRP by Jialal's team at UC Davis that showed CRP actually damages the blood vessel wall by blocking a critical "protector" protein and inhibiting nitric oxide.

"Interestingly, the new study indicates that activation of PAI-1 was unrelated to the nitric oxide inhibition identified in the earlier study," said Jialal. "This indicates that CRP has multiple, independent effects that cause heart disease."

Dan Yan Xu, a physician and postgraduate researcher in the pathology department at UC Davis, also contributed to the study.

This study was supported by grants from the National Institutes of Health (news - web sites), the Juvenile Diabetes Foundation and American Diabetes Association.



 
ROBOT.TXT
Chocolate Good for the Heart and Brain
August 29, 2011 (Paris, France) — In a city renowned for its love of food, it is only fitting that researchers presented the results of a new study in Paris, France, showing that chocolate is good for the heart and brain. In a presentation at the European Society of Cardiology (ESC) 2011 Congress, British investigators are reporting that individuals who ate the most chocolate had a 37% lower risk of cardiovascular disease and a 29% lower risk of stroke compared with individuals who ate the least amount of chocolate.

In the study, published online August 29, 2011 in BMJ to coincide with the ESC presentation, Dr Adriana Buitrago-Lopez (University of Cambridge, UK) and colleagues state: "Although overconsumption can have harmful effects, the existing studies generally agree on a potential beneficial association of chocolate consumption with a lower risk of cardiometabolic disorders. Our findings confirm this, and we found that higher levels of chocolate consumption might be associated with a one-third reduction in the risk of developing cardiovascular disease."

In this meta-analysis of six cohort studies and one cross-sectional study, overall chocolate consumption was reported, with investigators not differentiating between dark, milk, or white chocolate. Chocolate in any form was included, such as chocolate bars, chocolate drinks, and chocolate snacks, such as confectionary, biscuits, desserts, and nutritional supplements. Chocolate consumption was reported differently in the trials but ranged from never to more than once per day. Most patients included in the trials were white, although one study included Hispanic and African Americans and one study included Asian patients.

Of the seven studies, five trials reported a significant inverse association between chocolate intake and cardiometabolic disorders. For example, individual studies showed reductions in the risk of coronary heart disease (odds ratio 0.43; 95% CI 0.27–0.68), the risk of cardiovascular disease mortality (relative risk [RR] 0.50; 95% CI 0.32–0.78), and the risk of incident diabetes in men (hazard ratio 0.65; 95% CI 0.43–0.97).

Overall, the pooled meta-analysis results showed that high levels of chocolate consumption compared with the lowest levels of chocolate consumption reduced the risk of any cardiovascular disease 37% (RR 0.63; 0.44–0.90) and stroke 29% (RR 0.71; 0.52–0.98). There was no association between chocolate consumption and the risk of heart failure, and no association on the incidence of diabetes in women.

The researchers note that the findings corroborate the results of previous meta-analyses of experimental and observational studies in different populations showing a similar relationship between chocolate and cocoa consumption and cardiometabolic disorders.

"These favorable effects seem mainly mediated by the high content of polyphenols present in cocoa products and are probably accrued through the increasing bioavailability of nitric oxide, which subsequently might lead to improvements in endothelial function, reductions in platelet function, and additional beneficial effects on blood pressure, insulin resistance, and blood lipids," conclude Buitrago-Lopez and colleagues.