Abstract 1688: Impact of Change in High-Density Lipoprotein Cholesterol on Cardiovascular Disease Morbidity and Mortality: Systematic Review and Meta-Regression Analysis
To investigate the association between treatment-induced change in HDL-cholesterol and risks of coronary heart disease (CHD) death, CHD events (CHD death and nonfatal myocardial infarction), and total death adjusted for changes in LDL-cholesterol, using data from randomized controlled trials of lipid-modifying interventions. We conducted a systematic review and meta-regression analysis. Pairs of reviewers independently determined eligibility of randomized trials that tested lipid-modifying interventions to reduce cardiovascular risk, reported HDL- and LDL-cholesterol, mortality or myocardial infarctions separately for treatment groups, and followed participants for at least 6 months. The analysis included 108 randomized trials involving almost 300,000 individuals at risk for cardiovascular events. All analyses that adjusted for changes in LDL-cholesterol showed no association between treatment-induced change in HDL-cholesterol and risk ratios for CHD deaths, CHD events, or total deaths. Change in HDL-cholesterol explained almost no variability (< 2%) in any of the outcomes. The change in the quotient of LDL- and HDL-cholesterol did not explain more of the variability in any of the outcomes than did the change in LDL-cholesterol alone. Similarly, we found no association between change in triglycerides and the risk of CHD events whenever the model adjusted for the change in LDL-cholesterol. We found a statistically significant and clinically important association between change in LDL-cholesterol and risk ratios for CHD deaths (7.3% decrease per 10mg/dl LDL reduction, P = 0.001), CHD events (7.2% decrease per 10mg/dl LDL reduction, P < 0.001), and total deaths (4.4% decrease per 10mg/dl LDL reduction, P = 0.002) when adjusted for change in other lipid subfractions and types of lipid-modifying interventions. Change in LDL-cholesterol explained about one third of the variability in treatment effect across studies. Our results provide no support for treatment-induced changes in HDL-cholesterol reducing risk for CHD or deaths in interventions tested thus far in randomized trials. Our results support reduction in LDL-cholesterol as the primary goal of lipid-modifying interventions.