HDL-cholesterol, total cholesterol, and the risk of stroke in middle-aged British men

Background and Purpose-The purpose of this study was to examine the relation between serum HDL cholesterol and total cholesterol and risk of stroke. Methods-We carried out a prospective study in 7735 men, 40 to 59 years of age, drawn from 1 group practice in each of 24 British towns. Men with history of stroke were excluded (n=52). Results-During the mean follow-up period of 16.8 years, there were 343 stroke cases (fatal and nonfatal) in the 7683 men with no history of stroke. Higher levels of HDL cholesterol were associated with a significant decrease in risk of stroke even after adjustment for potential confounders (top fifth versus lowest fifth: adjusted relative risk=0.68, 95% CI 0.46 to 0.99). The inverse relation was seen only for nonfatal strokes (adjusted relative risk = 0.59, 95% CI 0.39 to 0.90; top fifth versus lowest fifth). Total cholesterol showed no graded association with fatal strokes, but men with levels greater than or equal to 8.1 mmol/L (top 5% of the distribution) showed increased risk of nonfatal stroke, although this was not statistically significant after adjustment (adjusted RR = 1.46, 95% CI 0.91 to 2.32). The beneficial effects of elevated HDL cholesterol on nonfatal stroke were seen in both smokers and nonsmokers and were more evident in men with hypertension than in normotensives. In hypertensive men, elevated HDL cholesterol (top fifth) was associated with a significant 50% reduction in risk of nonfatal strokes compared with men in the lowest fifth. Conclusions-Higher levels of HDL cholesterol were associated with a significant decrease in risk of nonfatal stroke. In contrast, elevated total cholesterol showed a weak positive association with nonfatal strokes. The marked inverse association between HDL cholesterol and stroke seen in hypertensives emphasizes the importance of those modifiable risk factors for stroke known to lower the concentrations of HDL cholesterol.