Abstract 12281: Association Between Extremely High HDL-C Levels and Mortality: A Systematic Review and Meta-Analysis

Abstract

Background: Recent research challenges previous findings that linked higher levels of high-density lipoprotein cholesterol (HDL-C) to lower cardiovascular (CV) mortality. New evidence suggests that extremely high HDL-C may increase the risk of adverse CV outcomes. Research Question: What is the relationship between very high levels of HDL-C and mortality in patients without coronary artery disease (CAD)? Goal: To perform a meta-analysis of the association between extremely high HDL-C and mortality endpoints in patients without CAD. Methods: We systematically searched PubMed, Embase, and Cochrane for studies comparing very high (≥80 mg/dL) HDL-C levels to normal (40-60 mg/dL) levels in individuals without CAD. Heterogeneity was examined using I2 statistics, and a random-effects model was employed. Review manager 5.4 was used for statistical analyses. Results: Among 1,044,699 patients without CAD from 7 studies, 88,676 (8.5%) had very high HDL-C levels, and 535,742 (51.3%) had normal HDL-C levels. Overall, there was no significant difference in all-cause mortality between the groups (OR 0.93; 95% CI 0.86-1.00; p=0.06). However, stratified by sex, very high HDL-C levels were associated with a significantly higher all-cause mortality in men (OR 1.30; 95% CI 1.01-1.67; p=0.04; Figure 1A) and a significantly lower all-cause mortality in women (OR 0.85; 95% CI 0.77-0.93; p=0.0005; Figure 1A) (p=0.002 for interaction). CV mortality was significantly lower in patients with very high HDL-C (OR 0.82; 95% CI 0.71-0.93; p=0.002), although again there was a significant interaction (p=0.0004) between women (OR 0.73; 95% CI 0.62-0.85; p=0.0001; Figure 1B), in whom high HDL-C was protective, and men (OR 1.34; 95% CI 0.99-1.80; p=0.06; Figure 1B). Conclusions: These findings indicated that very high levels of HDL-C (≥ 80 mg/dL) are associated with increased mortality in men, but lower mortality in women.