Causal Effect of Lipids and Lipoproteins on Atherosclerosis: Lessons from Genomic Studies.

Mendelian randomization studies demonstrate that apolipoprotein B-containing lipoproteins have both causal and cumulative effects on the risk of atherosclerotic cardiovascular disease. The clinical benefit of lipid-lowering therapies depends on both the absolute reduction in circulating apolipoprotein B-containing lipoproteins and the total duration of exposure to these particles. Because atherosclerosis seems to be caused by the retention of apolipoprotein B-containing lipoproteins rather than by the cholesterol content carried by those lipoproteins, high-density lipoprotein-mediated efflux of cholesterol from the arterial wall may not reduce the risk of atherosclerotic cardiovascular disease.