The relationship between cholesterol and stroke: implications for antihyperlipidaemic therapy in older patients.

Various studies on the relationship between serum cholesterol level and the risk of stroke have been published recently. Subsequent reviews have extrapolated information on stroke from the clinical trials originally aimed at lowering cholesterol for the primary and secondary prevention of myocardial infarction (MI) in middle-aged patients. We have reviewed the epidemiological knowledge on the relationship between serum cholesterol levels and stroke, and also focused on possible reduction of the risk of stroke with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor treatment. Possible benefits from such therapy are particularly relevant for the elderly population which is at particularly high risk for stroke. The effects of serum cholesterol levels on the risk for haemorrhagic and ischaemic stroke have been evaluated. Indirect epidemiological evidence indicates that serum levels of total cholesterol and its subfractions are determinants of stroke, but their associations are relatively weak. When exploring the possible association of serum cholesterol levels with the increased risk of stroke with aging, we concluded that, as in younger adults, elevated total cholesterol and decreased high density lipoprotein-cholesterol levels predispose to ischaemic stroke in the elderly. The mechanism through which serum cholesterol levels increase stroke risk is based on its actions on the artery walls. Indirect evidence suggests that the reduction in the stroke risk with HMG-CoA reductase inhibitors is larger than would be expected with reduction of elevated serum cholesterol level alone. Therefore, antioxidant and endothelium-stabilising properties of HMG-CoA reductase inhibitors may contribute in reducing the risk of stroke in recipients. Lowering high serum cholesterol with HMG-CoA reductase inhibitors has been beneficial in the primary and secondary prevention of MI. No trials have specifically tested the effect of cholesterol lowering with HMG-CoA reductase inhibitors on stroke occurrence. High serum cholesterol levels are a risk factor for ischaemic stroke, although the risk imparted is lower than that for MI. Although the relative risk of stroke associated with elevated serum cholesterol levels is only moderate, its population attributable risk is high given the increase in the elderly population worldwide. The effect of cholesterol reduction with HMG-CoA reductase inhibitors on prevention of ischaemic stroke should be evaluated in prospective, randomised, placebo-controlled trials in the elderly. The tolerability of lipid-lowering drugs in the elderly and the cost effectiveness of primary prevention of stroke using lipid-lowering drugs also needs to be assessed in the elderly.