Elevated serum low-density lipoprotein cholesterol (LDL-C) levels at middle-age constitute a strong risk factor for later cardiovascular events. In older populations, however, LDL-C levels are no longer predictive of cardiovascular mortality or may even seem protective. Whether the altered risk pattern of LDL-C in old age reflects a causal mechanism or is due to confounding and bias is subject to debate. In this review, we briefly discuss the possible explanations for the altered risk pattern of LDL-C observed in old age.

Using examples from the recent literature we illustrate how LDL-C levels ‘lose’ their predictive value as a cardiovascular risk factor in old age. We review three potential explanations for the changed cardiovascular risk pattern of LDL-C in older populations: survivorship bias, reverse causation, and effect modification.

The absent or protective effect of LDL-C on cardiovascular mortality in older populations found in observational studies might be explained by survivorship bias, reverse causation, and effect modification. However, this does not necessarily preclude the possibility that (specific) cholesterol-lowering treatment could decrease the risk of morbidity and mortality. Placebo-controlled trials may importantly add to our understanding of who may benefit from lipid-lowering therapy or statins at an older age.