50th Annual scientific sessions of the American college of cardiology.

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, 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 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 with atorvastatin 10 mg. 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 “ontreatment” 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 doubleblind 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-treatment LDL-C/HDL-C ratio; every reduction of 1.0 in the ratio resulted in a 31% reduction in risk.