Background: We investigated the relationship between low cholesterol and mortality and examined whether that relationship differs with respect to cause of death.
Methods: A community-based prospective cohort study was conducted in 12 rural areas in Japan. The study subjects were 12,334 healthy adults aged 40 to 69 years who underwent a mass screening examination. Serum total cholesterol was measured by an enzymatic method. The outcome was total mortality, by sex and cause of death. Information regarding cause of death was obtained from death certificates, and the average follow-up period was 11.9 years.
Results: As compared with a moderate cholesterol level (4.14-5.17 mmol/L), the age-adjusted hazard ratio (HR) of low cholesterol (<4.14 mmol/L) for mortality was 1.49 (95% confidence interval [CI]: 1.23-1.79) in men and 1.50 (1.10-2.04) in women. High cholesterol (≥6.21 mmol/L) was not a risk factor. This association was unchanged in analyses that excluded deaths due to liver disease, which yielded age-adjusted HRs of 1.38 (95% CI, 1.13-1.67) in men and 1.49 (1.09-2.04) in women. The multivariate-adjusted HRs and 95% CIs of the lowest cholesterol group for hemorrhagic stroke, heart failure (excluding myocardial infarction), and cancer mortality significantly higher than those of the moderate cholesterol group, for each cause of death.
Conclusions: Low cholesterol was related to high mortality even after excluding deaths due to liver disease from the analysis. High cholesterol was not a risk factor for mortality.