The Relationship between Very High Levels of Serum High-Density Lipoprotein Cholesterol and Cause-Specific Mortality in a 20-Year Follow-Up Study of Japanese General Population

Aims: There is no community-based cohort study to examine the effect of very high level of high-density lipoprotein cholesterol (HDL-C) on coronary heart disease (CHD) and other cause-specific mortality. Therefore, we investigated the relationship between HDL-C including very high level and cause-specific mortality in a 20-year cohort study of the representative sample of Japanese. Methods: We followed 7,019 individuals from the Japanese general population (2,946 men and 4,073 women). We defined HDL-C levels as follow: low (HDL-C ＜1.04 mmol/L), reference (1.04–1.55 mmol/L), high (1.56–2.06 mmol/L), very high (≥2.07 mmol/L). The multivariate adjusted hazard ratio (HR) for all-cause or cause-specific mortality was calculated using a Cox proportional hazards model adjusted for other traditional risk factors. Results: During follow-up, we observed 1,598 deaths. No significant association was observed between HDL-C and all-cause mortality. Serum HDL-C also showed no association with stroke. In contrast, the risk for CHD among high HDL-C was lower than reference, HRs were 0.51 [95% confidence interval (CI): 0.21–1.23] in men, 0.33 (95% CI: 0.11–0.95) in women, and 0.41 (95% CI: 0.21–0.81) when men and women were combined. However, very high HDL-C did not show significant association with CHD and other cause-specific mortality. Conclusions: HDL-C was not associated with all-cause and stroke mortality. In contrast, high serum HDL-C levels, at least up to 2.06 mmol/L, were protective against CHD, although further high levels were not. However, sample size of cause-specific death in very high HDL-C group was not enough even in this 20-year follow-up of 7,019 Japanese; larger cohort studies should be warranted.