High levels of high-density lipoprotein cholesterol increase all-cause and cardiovascular mortality in critically ill patients: a cohort study on the eICU database

Abstract Background Emerging evidence suggests that extremely high levels of high-density lipoprotein cholesterol (HDL-C) may increase the risk of adverse outcomes. However, the association between HDL-C levels and all-cause and cause-specific mortality has never been investigated in critically ill patients admitted to intensive care units (ICUs). Methods An observational cohort study was conducted using data from the eICU Collaborative Research Database. Individuals were divided into seven groups according to HDL-C concentrations (≤20, 21-30, 31-40, 41-50, 51-60, 61-70 and >70 mg/dL). Multivariable adjusted logistic models were conducted with odds ratios (ORs) and 95% confidence intervals (CIs). To further investigate the association between HDL-C and the risk of mortality, spline curves based on the generalized additive model, stratified analysis and sensitivity analysis were performed. Results Among 27,719 individuals included in the analysis, a total of 1713 (6.2%) all-cause deaths, 963 (3.5%) cardiovascular deaths and 750 (2.7%) noncardiovascular deaths were recorded within 30 days of ICU admission. Among the overall population, those with very high HDL-C levels (70 mg/dL) had an increased risk of all-cause mortality (OR, 1.36; 95% CI, 1.03-1.79) and cardiovascular mortality (OR, 1.63; 95% CI, 1.13-2.36) compared with those with HDL-C levels in the range of 51 to 60 mg/dL. These results were replicated among men and among women. The spline analysis revealed a U-shaped association between HDL-C levels and all-cause and cardiovascular mortality among the overall population and among men, with higher risk at both very high and low HDL-C levels. A nearly U-shaped association was observed among women, with a slightly attenuated risk at very high HDL-C levels. Sensitivity analysis also supported a U-shaped association between HDL-C levels and all-cause and cardiovascular mortality. Conclusions Results of this cohort study suggest that extremely high HDL-C levels are paradoxically associated with higher all-cause and cardiovascular mortality in critically ill patients.