Serum Cholesterol Levels and Risk of Cardiovascular Death: A Systematic Review and a Dose-Response Meta-Analysis of Prospective Cohort Studies

Introduction: Numerous studies have demonstrated that abnormal levels of cholesterol are associated with a high attributable risk for the occurrence of cardiovascular disease (CVD). However, there has been no comprehensive study to investigate the relationship between serum cholesterol levels and cardiovascular mortality. Therefore, we conducted a systematic review and dose-response meta-analysis. Methods: A systematic literature search of key databases, including EMBASE and MEDLINE, was conducted and included all the published epidemiological studies that contained estimates of the hazard ratios (HR) of serum cholesterol of CVD mortality. Data extraction, eligibility, and assessment of the risk of bias were assessed by two reviewers independently. All published risk estimates were hazard ratios and analyzed by quantitative meta-analysis using a random-effects model and dose-response relationships of serum cholesterol with CVD mortality. Results: A total of 14 independent reports, including 1,055,309 subjects and 9457 events, were analyzed. The pooled HR (95% CI) was 1.27 (95% CI, 1.19–1.36) for total cholesterol, 1.21 (95% CI, 1.09–1.35) for low-density lipoprotein cholesterol (LDL-C), and 0.60 (95% CI, 0.50–0.72) for high-density lipoprotein cholesterol (HDL-C). We observed a linear association between serum cholesterol (TC, HDL-C) levels and CVD mortality in this meta-analysis. Conclusions: Serum total cholesterol and LDL-C level is associated with increased CVD mortality, but HDL-C level is inversely associated with CVD mortality.