Association of high-density lipoprotein cholesterol concentration with different types of stroke and coronary heart disease: The Japan Public Health Center-based prospective (JPHC) study

Background and aims Although low high-density lipoprotein (HDL) cholesterol concentration is an established risk factor for coronary heart disease (CHD), information regarding subtypes of stroke is very limited, especially in Asian populations. Methods A prospective study was conducted among 30,736 individuals aged 40–69 years, who lived in nine communities in Japan and did not have a history of cardiovascular disease (CVD). CHD and stroke, including its subtypes, were assessed, and sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were estimated according to quintiles of HDL cholesterol using Cox proportional models adjusted for other CVD risk factors. Results We identified 296 CHD and 1712 stroke events over a median 15 yr of follow-up. HDL cholesterol concentration showed an inverse association with CHD in men and women. A low HDL cholesterol concentration slightly raised the risk for total strokes in men, but not in women. When analyzed by subtypes, we observed an inverse relationship between HDL cholesterol concentration and the incidence of lacunar infarction, with an adjusted HR for the lowest quintile of HDL cholesterol concentration compared with the highest quintile of 1.63 (95% CI, 1.00–2.66) in men and 1.97 (95% CI, 1.19–3.26) in women. HDL cholesterol concentration was positively associated with the risk of intracerebral hemorrhage (ICH) in a linear manner in women (p for trend = 0.028), but not in men. Conclusions The associations of HDL cholesterol concentration with lacunar infarction and ICH may be related to different functional properties of HDL rather than to its protective function against lipid-rich atherosclerosis.