Impact of increases in high-density lipoprotein cholesterol on cardiovascular outcomes during the armed forces regression study

Introduction: High-density lipoprotein (HDL) cholesterol is a well-established inverse risk factor for cardiovascular disease. The extent to which cardiovascular risk can be modified through changes in HDL, however, is less clear. We further examined the role of aggressive HDL raising therapy on cardiovascular outcomes in the 143 patients enrolled in the Armed Forces Regression Study (AFREGS). Methods: Reanalysis of the AFREGS population. Patients with stable coronary disease were randomized to receive gemfibrozil, niacin, and cholestyramine in combination or matching placebos, on top of aggressive dietary and exercise modification for a 30-month period. Blood work was performed at baseline and repeated after 1 year of therapy. Results: Patients were divided into 3 groups based on their therapeutic response: no HDL increase, mild HDL increase, and large HDL increase (% change in HDL ≤0, ≤ the lower 2 tertiles of HDL increase, and > the upper tertile of HDL increase, respectively). A progressive decrease in cardiovascular events was noted across these groups (30.4%, 19.4%, and 3.2%, respectively, P =.01). Kaplan-Meier analysis according to percentage change in HDL demonstrated a similar improvement in event-free survival (P =.01). Proportional hazards modeling also demonstrated that increasing HDL predicted a lower hazard of cardiovascular events, even after adjusting for changes in low-density lipoprotein ([LDL] P <.01). For every 1% increase in HDL achieved, a 2% decrease in events was recognized. Conclusions: These data suggest that in a population of patients with stable atherosclerosis, the greater the percentage increase in HDL achieved, the greater the cardioprotective benefit. This further supports HDL raising as a beneficial therapeutic strategy.