The primary and especially secondary prevention of coronary heart disease (CHD) through aggressive reduction of low-density lipoprotein cholesterol (LDL-C) has been one of the major public health accomplishments of the last 3 decades. Natural experiments have consistently shown that populations with low LDL-C levels experience a lower risk of CHD, whereas those with genetic mutations that confer higher LDL-C levels have a substantially higher risk of CHD events. Results from clinical trials have convincingly demonstrated that LDL-C is dose-dependently linked to CHD risk,1,2 suggesting a causal role in the atherogenesis pathway.