A dose–response meta-analysis to evaluate the relationship between high-density lipoprotein cholesterol and all-cause and cardiovascular disease mortality

PURPOSE Previous studies have not fully described the relationship between high-density lipoprotein cholesterol (HDL-C) and death risks from all cause and cardiovascular disease (CVD). This study quantitatively evaluates HDL-C-mortality associations. METHODS Embase and PubMed databases were searched for relevant articles published up to 1 June 2019. Random-effects models were used to pool relative risks (RRs) and 95% confidence intervals (CIs). We used restricted cubic splines to model the dose-response association. RESULTS We identified 32 prospective cohort studies including 369,904 participants and 33,473 total deaths (9426 CVD deaths). Compared to the lowest HDL-C levels, all cause and CVD mortality risks were reduced by 18% (RR 0.82; 95% CI, 0.73-0.93) and 36% (0.64, 0.46-0.89), respectively, for the highest HDL-C levels. All cause and CVD mortality risks were reduced by 15% (0.85, 0.79-0.92) and 23% (0.77, 0.69-0.87), respectively, with each 1 mmol/L increment of HDL-C. We found evidence of nonlinear and negative dose-response associations of HDL-C with all cause and CVD mortality (Pnonlinearity < 0.001), and the lowest death risks from all cause and CVD were observed at approximately 1.34 and 1.55 mmol/L, respectively. CONCLUSION HDL-C is inversely associated with all cause and CVD mortality risks under approximately 2.05 and 2.33 mmol/L, respectively. Optimal doses require investigation via clinical practice or high-quality research.