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.

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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.

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