Background and purpose: The role of circulating lipids and lipoproteins in the pathogenesis of ischemic stroke remains uncertain despite 3 decades of research. We examined this issue in a large population-based cohort.
Methods: Between 1987 and 1989, 14 175 middle-aged men and women, free of clinical cardiovascular disease, took part in the first examination of the Atherosclerosis Risk in Communities (ARIC) study cohort. Baseline measurements included plasma levels of LDL cholesterol, HDL cholesterol, apolipoprotein B, apolipoprotein A-1, and triglycerides and myriad risk factors for cardiovascular disease. The cohort was followed for cardiovascular disease end points.
Results: Over an average follow-up of 10 years (142 704 person-years at risk), we documented clinical ischemic stroke in 305 participants (161 men and 144 women). After multivariable adjustment for stroke risk factors, categorical and spline regression analyses of the entire sample, as well as the sample of men alone, revealed weak and inconsistent associations between ischemic stroke and each of the 5 lipid factors. Among women, the most consistent findings were decreasing risk of ischemic stroke within the top half of the distribution of HDL cholesterol and increasing risk within the lower range of the triglyceride distribution.
Conclusions: The relation of circulating cholesterol to ischemic stroke does not resemble its well-known relation to coronary heart disease. Either the pathogenesis of a substantial proportion of ischemic strokes does not involve classic atherosclerotic mechanisms, or the effect of plasma lipids on atherogenesis is substantially different in the intracranial vascular bed.