Adiponectin draws increasing interest as novel CV risk factor

Adiponectin draws increasing interest as novel CV risk factor

Bruce Jancin

ORLANDO, FLA. — Now that C-reactive protein has entered the clinical mainstream as a cardiovascular risk assessment tool, adiponectin may be emerging as the next cardiovascular risk factor.

A protein secreted by fat cells, adiponectin may play a central role in the interrelated epidemics of obesity, diabetes, and coronary disease. Animal and human studies show that adiponectin enhances insulin secretion, reduces blood pressure, and helps burn visceral fat. A low level of plasma adiponectin is linked to low HDL cholesterol levels, high triglyceride levels, and a shift toward more highly atherogenic small, dense LDL particles.

A large case-control study has now shown that high plasma adiponectin has been associated with a reduced risk of acute MI among men, several investigators said at the annual scientific sessions of the American Heart Association.

Dr. Tobias Pischon of the Harvard School of Public Health, Boston, reported on 18,130 men who were free of heart disease in 1994, when they provided blood samples as participants in the Health Professionals Follow-up Study. During the next 6 years, 266 of the men died of coronary heart disease or had a first nonfatal acute MI. Each was matched with two control subjects on the basis of age, smoking status, and date of blood draw.

In a multivariate analysis further adjusted for HDL, triglycerides, glycosylated hemoglobin, C-reactive protein, physical activity, alcohol consumption, hypertension, and other factors, men in the highest quintile of adiponectin levels were at only half the risk of MI, compared with those in the lowest quintile.

A key unanswered question is whether a low adiponectin level is merely a marker of cardiovascular and diabetes risk, or is causally related and thus a prime target for drug therapy. No clinical studies have examined this issue, but animal data are encouraging. Dr. Kengo Matsumoto has genetically manipulated adiponectin levels in laboratory animals. When he lowered the adiponectin level, the animals developed insulin resistance, hypertriglyceridemia, low HDL, neointimal thickening, and atherosclerosis.

“And overexpression of adiponectin prevented progression of atherosclerosis in vivo,” added Dr. Matsumoto of Kure (Japan) National Medical Center.

Dr. Klaus A. Dugi noted that the peroxisome proliferator-activated receptor (PPAR) agonists rosiglitazone and pioglitazone can raise adiponectin levels by up to threefold, an effect that may mediate at least part of the drugs’ clinical benefits.

If so, perhaps a small-molecule drug can be devised that activates the adiponectin receptor–which was recently cloned and published–without the weight gain and other side effects of currently available PPAR agonists, said Dr. Dugi of the University of Heidelberg (Germany).

Dr. Lewis Kuller’s research in the Healthy Women Study has focused on adiponectin’s value in identifying over-weight or obese postmenopausal women at very high risk for diabetes and cardiovascular disease.

Increasingly, measuring adiponectin, insulin, and glucose levels appears to be a simple yet powerful way to assess insulin resistance. Together with measuring the coronary calcium level via electron beam CT, these techniques may turn out to be effective in identifying subsets of over-weight patients who require aggressive pharmacologic and nonpharmacologic therapies, said Dr. Kuller, professor of epidemiology at the University of Pittsburgh.

Although an adiponectin assay is available in most laboratories, it’s not ready for prime time clinical practice, the researchers stressed.

“Adiponectin has substantial potential value, but until we get further studies about its role, it’s still only an emerging risk factor,” Dr. Kuller observed.

BY BRUCE JANCIN

Denver Bureau

COPYRIGHT 2004 International Medical News Group

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