Huan Hu, Tohru Nakagawa, Toru Honda, Shuichiro Yamamoto, Takeshi Kochi, Takayuki Ogasawara, Naoki Gommori, Makoto Yamamoto, Toshiaki Miyamoto, Hiroko Okazaki, Hiroshi Ide, Seitaro Dohi, Maki Konishi, Isamu Kabe, Tetsuya Mizoue
BackgroundElevated low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for coronary heart disease, but its role in stroke remains unclear. This study examined the association between LDL-C levels and the risk of cardiovascular disease (CVD) and its subtypes in a large cohort of Japanese workers.MethodsWe analyzed data from 69,605 participants in the Japan Epidemiology Collaboration on Occupational Health study. Baseline LDL-C levels were categorized as <70, 70-99, 100-119, 120-139, 140-159, and ≥160 mg/dL. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsOver a mean follow-up of 8.5 years (range, 0.1-13.4 years), 406 participants developed CVD. Compared with LDL-C levels of 100-119 mg/dL, participants with LDL-C <70 mg/dL had a higher risk of intracerebral hemorrhage (HR, 3.56; 95% CI, 1.31-9.66), whereas no association was observed between LDL-C levels and subarachnoid hemorrhage. For ischemic stroke, a U-shaped association was observed; adjusted HRs (95% CIs) versus 100-119 mg/dL were 2.26 (0.97-5.25), 1.53 (0.92-2.56), 0.95 (0.56-1.60), 1.71 (1.04-2.81), and 1.52 (0.85-2.72) for LDL-C levels of <70, 70-99, 120-139, 140-159, and ≥160 mg/dL, respectively. In contrast, the risk of myocardial infarction increased linearly with increasing LDL-C levels.ConclusionsVery low LDL-C levels were associated with an increased risk of intracerebral hemorrhage, whereas a suggestive U-shaped association was observed between LDL-C levels and ischemic stroke. The risk of myocardial infarction increased with higher LDL-C levels.