Lower HDL Cholesterol Increases Risk of Cardiovascular Event

March 14, 2006

March 14, 2006 (Atlanta) — High-density lipoprotein (HDL) cholesterol levels represent a potential target for further reducing cardiovascular disease risk in patients who achieve optimal low-density lipoprotein (LDL) cholesterol reductions with statin therapy, an ad-hoc analysis of data from the Treating to New Targets (TNT) study suggests.

"Clinicians know that HDL is important, but many think that it ceases to be important if we get LDL levels to below 100 mg/dL," chief investigator Philip Barter, MD, director of the Heart Research Institute in Sydney, Australia, told Medscape.

"Our study, in which half the population achieved LDL levels below 80 mg/dL, clearly shows that even if LDL is low, HDL is still important," Dr. Barter said.

The study, presented here at the 55th Annual Scientific Session of the American College of Cardiology, included 10,001 patients randomized to treatment with atorvastatin 80 mg or atorvastatin 10 mg.

Men and women aged 35 to 75 years with clinically evident coronary heart disease (CHD) were eligible for inclusion. CHD was defined as one or more of the following: prior myocardial infarction, prior or current angina with objective evidence of atherosclerotic CHD, or a history of coronary revascularization.

The patients were seen every 3 months in the first year and every 6 months thereafter, for a median of 4.9 years.

The primary end point was the occurrence of a first major cardiovascular event, defined as death from CHD; nonfatal, non–procedure related MI; resuscitation after cardiac arrest; or stroke.

The study showed that every 1 mg/dL increase in HDL cholesterol concentration was associated with an approximate 2% reduction in the relative risk of a major cardiovascular event. "This compares with a reduction of 0.7% in the risk of major events for every 1 mg/dL reduction in on-treatment LDL cholesterol we had previously reported," Dr. Barter said.

When the 4387 patients with LDL cholesterol levels of 80 mg/dL or lower were analyzed separately, the same inverse relationship between HDL cholesterol levels and major cardiovascular disease rates were observed. For example, 10% of such patients with HDL levels below 38 mg/dL on either dose had a major event compared with 5% of those with HDL levels 55 mg/dL or higher. In addition, there was a 31% reduction in the risk of major events for every 1.0 reduction in the LDL-HDL cholesterol ratio ( P < .001).

Nieca Goldberg, MD, an American Heart Association spokesperson, said that the results reinforce the importance of paying attention to HDL cholesterol levels in clinical practice.

"If you look at all the LDL cholesterol&#8211;lowering studies, only 35% to 45% of patients benefit with a reduction in cardiovascular disease risk, so clearly other factors are at play," she told Medscape. Dr. Goldberg is a clinical assistant professor of medicine at New York University School of Medicine and chief of women's cardiac care at Lenox Hill Hospital in New York City.

At the present time, however, clinicians are limited in what they can offer their patients with low HDL levels, Dr. Goldberg said. "There's diet, exercise, and, if the patient can tolerate it, niacin. On the bright side, there are promising drugs in clinical trials," she said.

The study was sponsored by Pfizer, Inc.

ACC 55th Annual Scientific Session: Abstract 914-203. Presented March 12, 2006.

Reviewed by Ariana Del Negro