American College of CardiologyLow HDL-Cholesterol and the LDL-Cholesterol/ HDL-Cholesterol Ratio as Predictors of Cardiovascular Events

Speaker: Philip Barter, MD, PhD, Director, Heart Institute, Camperton, Australia, and Professor of Medicine, University of Sydney, Sydney, Australia

Although the control of low-density lipoprotein-cholesterol (LDL-C) remains a pivotal focus of preventing cardiovascular disease (CVD), the Treating to New Targets (TNT) study suggests that high-density lipoprotein-cholesterol (HDL-C) and the ratio of LDL-C to HDL-C provide additional information in predicting cardiovascular events and should be considered potential targets for future drug therapy.

In the randomized, double-blind, parallel-group, multicenter TNT study, 10,001 patients with clinically evident stable coronary heart disease received atorvastatin (Lipitor drug, Pfizer) at a dose of 10 mg/day during an eight-week, open-label, run-in phase. After the run-in phase, patients with an LDL-C concentration above 130 mg/dl were selected to receive generic atorvastatin 10 or 80 mg/dl. These patients were observed for a median of 4.9 years. The initial results showed that intensive lipid-lowering therapy provided clinical benefits far beyond that afforded by treatment.

An analysis was then designed to investigate the relationship between the frequency of major cardiovascular events and HDL-C levels in treated patients during the TNT study and to determine whether this relationship was modified by “on-treatment” LDL-C levels. The frequency of major events was calculated by quintiles of on-treatment HDL-C levels below 38 mg/dl, between 38 and 43 mg/dl, between 43 and 48 mg/dl, between 48 and 55 mg/dl, and at 55 mg/dl or higher. HDL-C levels were determined at the third month during the double-blind treatment phase.

The data strongly suggest that HDL-C levels and the ratio of LDL-C to HDL-C are predictive of CVD risk. Although lower on-treatment HDL-C levels were correlated with an increased incidence of major cardiovascular events, an increment of 1 mg/dl in on-treatment HDL-C was associated with a decrease of approximately 2% in the risk of experiencing a major event. This compared with a reduction of 0.7% in the risk of a major event for every 1-mg/dl reduction in on-treatment LDL-C levels in this study.

HDL-C levels remained predictive of the frequency of major cardiovascular events at both high and low LDL-C concentrations. This suggests that HDL-C levels are a major consideration even when LDL-C levels are being managed intensively. There was also a comparable direct relationship between the frequency of major cardiovascular events and the on-treat-ment LDL-C/HDL-C ratio; every reduction of 1.0 in the ratio resulted in a 31% reduction in risk.

Long-Term, Extended-Release Niacin Raises HDL-Cholesterol Levels

Speaker: Leonard M. Keilson, MD, Director, Maine Center for Lipids and Cardiovascular Health, Scarborough, Maine

Ten years of continuous treatment with extended-release (ER) niacin (Niaspan, Kos Pharmaceuticals), combined with two to 10 years of statin therapy, resulted in long-term positive benefits, with 5% of patients proving to be niacin hyper-responders (i.e., achieving HDL-C levels 50% above their baselines values).

Overall, 11,000 patient records covering 15 years were screened at The Maine Center for Lipids. The investigators collected data on body mass index (BMI), blood glucose levels, and medications used, and they performed a manual chart review. The medical database identified 270 patients who had received ER niacin therapy for as long as 10 years continuously.

The purpose of the study was to describe ER niacin-treated patients with a greater than 50% increase in HDL-C over baseline measurements. The medical database uncovered 13 ER niacin-treated patients who had made more than three office visits and included baseline values, values during treatment, and an HDL-C level greater than 50% of the baseline value. In this group, 69% of patients received a statin for the entire treatment period and 100% received a statin for at least two years.

These 13 niacin hyperresponders made 22 office visits per patient over five years (median, seven years). At the baseline, HDL-C levels were 32.2 ± standard deviation (SD) 11 mg/dl and triglyceride levels were 288 ± SD 71 mg/dl. Over the treatment period, average HDL-C levels increased by 90% (range, 52%-153%), with a median increase of 63%.
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Compared with baseline values, triglyceride levels declined by 43% and body weight decreased by 4%. Of these hyper-responders, 4% were diabetic patients whose glucose levels were controlled with diet.