Misleading associations between cholesterol and vascular outcomes in dialysis patients: the need for randomized trials.

Higher cholesterol is strongly associated with an increased risk of coronary heart disease (CHD) in nonrenal populations, so the lack of a clear positive association between total cholesterol and mortality among dialysis patients is unexpected. This review of prospective studies of the association between total cholesterol and mortality among dialysis patients suggests that there is a negative association at below average cholesterol levels and a flat or weakly positive association at higher levels. In nonrenal populations total cholesterol is not positively associated with vascular causes of death other than CHD, so the lack of a strongly positive association at above average cholesterol concentrations in dialysis patients may be explained by the high proportion of deaths due to non-CHD vascular causes. The observation of a negative association between total cholesterol and mortality at below average cholesterol concentrations in some studies is consistent with confounding by both vascular and nonvascular morbidity (i.e., reverse causality). We argue that evaluating the importance of cholesterol for vascular disease risk in dialysis patients can only be achieved through the eradication of confounding by randomization, and that ongoing trials of cholesterol-lowering therapy will provide a definitive answer to this question.