Although associations of
cholesterol and
coronary heart disease (CHD) are well accepted, the association between
cholesterol and
stroke has been a subject of some
confusion. Epidemiologic evidence suggests no association between plasma concentrations of
cholesterol and
stroke, and earlier clinical trials were also negative. Two early meta-analyses of clinical trials designed to evaluate the effects of
cholesterol lowering on CHD concluded that
cholesterol lowering had no effect. More recently newer, more potent and better tolerated agents (
HMG-CoA reductase inhibitors,
reductase inhibitors) have become available and have been tested for their efficacy in reducing
cholesterol and CHD in both primary prevention and
secondary prevention trials. Meta-analyses of these trials, in contrast to the earlier trials, reveal a powerful statistically significant effect to reduce
stroke as well as CHD in
secondary prevention (30%); the direction of the effect is the same in trials of primary prevention or trials that randomized patients with and without CHD (mixed primary and
secondary prevention trials) where the risk reductions for
stroke, although not reaching statistical significance are 11 and 30%, respectively. An important difference in the newer analysis is the availability of several trials of
secondary prevention in which
low density lipoprotein cholesterol was lowered 25-30% and in which CHD event reduction was similarly reduced by 30%. Mechanisms for
stroke reduction likely involve retardation of plaque progression in the intracranial and extracranial carotid arteries, plaque stabilization, and, in addition,
stroke may be reduced partly as a consequence of CHD reduction.