Repeated measures of extremely high levels of high-density lipoprotein cholesterol and subsequent all-cause mortality and cardiovascular events: A longitudinal study

Background and aims: Extremely high level high-density lipoprotein (HDL) cholesterol had been cautioned as risk factor for all-cause mortality and cardiovascular disease. However, both the physician and the patient may underestimate the risk due to the emphasis on good cholesterol, resulting in passive treatment or adoption of a less healthy lifestyle. The aim of this study is to re-evaluate the association with longitudinal data to account for fluctuations in HDL cholesterol and covariates. Methods: We conducted a retrospective longitudinal study at a large teaching hospital in Tokyo, Japan, from 2005 to 2016. We included all adults who participated in health check-ups. Outcomes were all-cause mortality and cardiovascular events. HDL cholesterol was repeatedly measured at each visit and categorized into five groups. The time-varying Cox model was applied to longitudinal analyses. Results: We included a total of 83,100 participants; the mean age was 45.5 (standard deviation: 12.4) years; 41,013 (49.4%) were male, and 4475 participants belonged to the extremely high level HDL cholesterol group (> 90 mg/dl). During a median follow-up of 1746 (interquartile range: 740-3112.5) days, 382 (0.5%) participants died, and 2023 (2.4%) experienced cardiovascular events. Although the extremely high level HDL cholesterol group had significantly lower hazard ratios (HRs) for all-cause mortality (HR: 0.49, 95% confidence interval (CI): 0.26-0.90) and cardiovascular events (HR: 0.71, 95% CI: 0.54-0.94) compared to the low group (< 40 mg/dl), HRs were higher than in the very high level HDL cholesterol group. Conclusions: Our study demonstrated that extremely high level HDL cholesterol has significantly lower risks of all-cause mortality and cardiovascular events compared to low level, but higher risks compared to very high level, as previously reported.