High-density Lipoprotein Subclasses and Risk of Stroke and its Subtypes in Japanese Population

Abstract

High-density lipoprotein (HDL) cholesterol is an established protective factor for ischemic stroke. However, the contribution of HDL subclasses to stroke risk and its subtypes is uncertain. A prospective nested case-control study of 40- to 85-year-old Japanese was undertaken using frozen serum samples collected from 5280 men and 7524 women. They participated in cardiovascular risk surveys from 1985 to 1999 (1 community) and 1989 to 1998 (2 communities) under Circulatory Risk in Communities Study. HDL cholesterol subclasses were classified by high-performance liquid chromatography into 3 subgroups: S-HDL (very small or small HDL), M-HDL (medium HDL), and L-HDL (large or very large HDL) cholesterol. One control subject per case was matched by sex, age, community, serum storage year, and fasting status. In 2005, we identified 241 strokes (155 ischemic and 86 hemorrhagic). S-HDL and M-HDL cholesterol levels were inversely associated with total stroke risk, ischemic stroke, specifically lacunar infarction, and hemorrhagic stroke. After adjustment for cardiovascular risk factors, these associations remained statistically significant. Multivariable conditional odds ratios (95% confidence interval) for 1 SD (0.12 mmol/L) increment of S-HDL cholesterol levels were 0.34 (0.23-0.52) for total stroke, 0.38 (0.23-0.63) for ischemic stroke, 0.33 (0.18-0.61) for lacunar infarction, 0.30 (0.14-0.65) for hemorrhagic stroke, and 0.30 (0.12-0.77) for intraparenchymal hemorrhage. The respective multivariable odds ratios for 1SD (0.10 mmol/L) increment of M-HDL cholesterol levels were 0.56 (0.41-0.75), 0.63 (0.45-0.88), 0.59 (0.40-0.87), 0.41 (0.21-0.80), and 0.38 (0.16-0.90). No associations were found between L-HDL cholesterol levels and risk of total stroke and its subtypes. Small- to medium-sized HDL, not large HDL, cholesterol levels were inversely associated with total stroke risk.