High-Density Lipoprotein and Cardiovascular Disease—Where do We Stand?

Decades of research have shown that high-density lipoprotein cholesterol (HDL-C) levels in humans are associated with atherosclerotic cardiovascular disease (ASCVD). This association is strong and coherent across populations and remains after the elimination of covariates. Animal studies show that increasing HDL particles prevent atherosclerosis, and basic work on the biology of HDL supports a strong biological plausibility for a therapeutic target. This enthusiasm is dampened by Mendelian randomization data showing that HDL-C may not be causal in ASCVD. Furthermore, drugs that increase HDL-C have largely failed to prevent or treat ASCVD.