Abstract

Introduction: Low density lipoprotein cholesterol (LDL-C) is an established causal factor for coronary heart disease (CHD) and ischemic stroke. A positive linear association between LDL-C and risk of CHD or ischemic stroke was reported from western populations but among Japanese the evidence still insufficient especially on the risk of ischemic stroke. This study used a longitudinal data from the Aichi Worker’s Cohort Study to explore the associations of LDL-C levels with the incidence of CHD, and stroke subtypes. Methods: Pooled data of 6325 adults (5001 men and 1324 women) who responded to the second (2002) and third (2007) wave surveys of the study were used for the current analysis. Propensity scores for LDL-C categories were generated using multinomial logistic regression that included age, sex, smoking, alcohol drinking, physical activity, body mass index, high-density lipoprotein cholesterol, triglycerides, history of diabetes and hypertension, antihypertensive medication, taking dyslipidemia medication and survey year. Hazard ratios (HRs) and the 95% confidence intervals (95% CIs) were estimated from inverse probability weighted (IPW) cox proportional hazards model for LDL-C categories associations with risks of CHD, stroke and its subtypes, and CVD. We also used restricted cubic spline to examine the possible nonlinear relationship. Results: During a median of 14 years of follow-up, 73 strokes (40 ischemic stroke, 30 hemorrhagic stroke and 3 unknown) and 60 CHD were observed. In comparison with LDL-C < 120 mg/ dl, LDL-C ≥160 mg/dl was significantly associated with the increased risk of CVD (HR 1.79, 95% CI: 1.12-2.86) and CHD (HR 3.82, 95% CI: 1.80-8.06), but not with stroke (HR 1.05, 95% CI: 0.54-2.06), hemorrhagic stroke (HR 0.47, 95% CI: 0.13-1.67) or ischemic stroke (HR 1.56, 95% CI: 0.66-3.68). The results of restricted cubic spline analysis showed that the risks of CVD and CHD gradually increased from LDL-C of 120 mg/dl. On the other hand, the risk of ischemic stroke was flat until around LDL-C of 160 mg/dl and then increased afterward. The risk of hemorrhagic stroke was flat from LDL-C of 120 mg/dl or above, but showed an increased risk trend towards lower levels of LDL-C. Conclusions: Based on this recent, long-term prospective study among middle-aged Japanese workers and by applying the IPW method to adjust for several confounding variables, we found that LDL-C was linearly and positively associated with CHD incidence while higher LDL-C levels tended to be at an increased risk of ischemic stroke, though non-significant.

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