Raising HDL-C Levels Slows CAD Progression and Reduces Mortality

Peggy Peck

April 03, 2003

April 3, 2003 (Chicago) — Results of two studies of high-density lipoprotein cholesterol (HDL-C)-targeted therapies indicate that attacking heart disease by increasing HDL-C levels appears to slow progression of atherosclerosis and reduce mortality.

Although the protective effect of HDL-C is well known, "most researchers ignore this fact," said Henrietta Reicher-Reiss, MD, from Sheba Medical Center in Tel Hashomer, Israel. It is a costly oversight since "about half of heart attack victims have normal [low-density liprotein cholesterol (LDL-C) levels]," she said.

Richard Krasuski, MD, from Wilford Hall Army Medical Center in San Antonio, Texas, and lead investigator of the second study, said, "HDL is a stronger predictor of outcome than LDL" and that aggressively targeting HDL-C can slow the progression of coronary artery disease.

In Dr. Krasuki's study, 30 months of HDL-C targeted therapy increased average HDL-C by 37% while decreasing LDL-C by 5% and dropping total cholesterol levels by an average of 16%. At the same time, triglycerides were reduced by 45% but fasting blood sugar increased by 18%. "Coronary stenosis decreased by 1% compared to a 1% increase in the placebo arm, " Dr. Krasuski said.

A combined endpoint of unstable angina, transient ischemic attack, stroke, percutaneous intervention, coronary bypass, or death was reached by nine patients receiving active therapy and 19 placebo patients.

In his study, 143 patients with heart disease were randomized to an HDL-C targeted regimen of gemfibrozil, niacin, and cholestryamine or placebo. Both groups were also put on a cardiovascular workout program and a heart-healthy diet. Ninety-two percent of the patients were men, and the average age was 63 years, Dr. Krasuski said.

At baseline, total cholesterol was 195 ± 31 mg/dL, LDL-C was 127 ± 27 mg/dL, HDL-C was 34 ± 6 mg/dL, and triglycerides were 169 ± 82 mg/dL. Systolic blood pressure was 139 ± 16 mm Hg, and fasting blood sugar 80 ± 14 mg/dL. There was no difference in baseline characteristics between the two groups.

After 30 months, patients in the placebo group increased total cholesterol by 3%, LDL-C was 21% higher; HDL-C was up by 2%, triglycerides increased by 3%, and fasting blood sugar increased by 8%.

The Israeli study by Dr. Reicher-Reiss and colleagues is an analysis of extended follow-up data from the Bezafibrate Infarction Prevention (BIP) trial. More than 3,000 patients were randomized to 400 mg of bezafibrate or placebo. The results of 1,509 patients treated with bezafibrate were analyzed in tertiles of on-treatment increments comparing the ratio of HDL-C to total cholesterol and those results were compared to outcomes in 1,517 patients in the placebo group.

After 8.2 years, the mortality was 15.2% in the placebo group and 13.9% in the bezafibrate group (P = .033).

"Mortality decreased as patient compliance with bezafibrate therapy increased as indicated by favorable change in the HDL-C to total cholesterol ratio," Dr. Reicher-Reiss told Medscape. "The patients with the best compliance had the most favorable HDL-C/total cholesterol ratio and were rewarded with the lowest mortality."

The mortality rate in the tertile with highest treatment compliance was 11%. She said most of the survival benefit came from "a significant decline in deaths from heart disease."

Richard Pasternak, MD, an associate professor at Harvard Medical School in Boston, said the studies are a wake-up call for many cardiologists. "The emphasis has been on statins, which reduce total cholesterol, significantly reduce LDL and have a modest effect on HDL," he told Medscape. "These studies point out that statins are not the only way to treat cholesterol and point out, again, the important protective role of HDL."

Noting the lifestyle component of the Krasuski study, Dr. Pasternak added, "this is another reminder that prevention of heart disease does not always come in pill form."

But, Dr. Pasternak said, drugs designed to target HDL-C have a number of adverse effects. Niacin, for example, causes flushing, and fibrates are associated with gastrointestinal side effects. That side-effect profile might be a factor against this approach. Statins, on the other hand, tend to be very well tolerated, he said.

ACC 52nd annual scientific sessions: Abstract 876-1, presented April 2, 2003; abstract 876-3, presented April 2, 2003.

Reviewed by Gary D. Vogin, MD



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