Table 2: Controversies surrounding the “HDL hypothesis.”

HDL and atherosclerosis: proThe “HDL hypothesis” questioned

Strong biological plausibility for HDL as a therapeutic targetMendelian Randomization does not support HDL-cholesterol as a causal risk factor

The epidemiological association between HDL-C and CVD is strong and coherent HDL-C loses its predictive value if LDL-C is low

Animal data is unequivocal: HDL protects against atherosclerosisThe clinical trial data with drugs that raise HDL-C (fibrates, niacin, torcetrapib, and dalcetrapib) is neutral