HDL Cholesterol: Causal or Just a Marker for Coronary Risk?

Although randomized trials have established a causal relation between high LDL cholesterol levels and high cardiovascular risk, a similar causal association between high HDL cholesterol levels and low cardiovascular risk has not been proven. Moreover, if HDL cholesterol is merely a marker for some underlying factor that lowers cardiovascular risk, therapies designed to raise HDL cholesterol levels might not affect cardiovascular outcomes.

Investigators identified a genetic variant that is associated with substantially elevated HDL cholesterol levels but that does not affect other lipid or nonlipid cardiovascular risk factors. If high HDL cholesterol levels directly lower risk for myocardial infarction (MI), individuals with this genetic vari…