Association between very high HDL-C levels and mortality: A systematic review and meta-analysis.

• High HDL-C up to 126 mg/dL reduces fatal/non-fatal coronary heart disease events. • No decrease in all-cause mortality compared to normal levels. • Men with HDL-C ≥ 94 mg/dL may face increased cardiovascular mortality. • Women with HDL-C ≥ 116 mg/dL may face increased cardiovascular mortality. Recent research has raised questions about the assumed cardiovascular (CV) benefits of high-density lipoprotein cholesterol (HDL-C) and the potential for adverse outcomes with extremely high levels. We conducted a meta-analysis to investigate the association between very high HDL-C levels (≥80 mg/dL) and mortality outcomes in individuals without coronary artery disease (CAD). We systematically searched PubMed, Embase, and Cochrane databases for studies comparing very high HDL-C levels to normal levels (40–60 mg/dL) in CAD-free individuals. We assessed heterogeneity using I² statistics with a random-effects model. Our analysis included 1,004,584 individuals from 8 studies, of whom 133,646 (13.3%) had very high HDL-C levels. All-cause mortality did not significantly differ between groups (p = 0.55), nor did cancer mortality (p = 0.45). Cardiovascular mortality showed no change in those with very high HDL-C (hazard ratio [HR] 1.05; 95% confidence interval [CI] 0.94–1.17; p = 0.37). Fatal and non-fatal coronary heart disease events were less frequent in the very high HDL-C group (HR 0.79; 95% CI 0.73–0.86; p < 0.00001). Subgroup dose-response analysis revealed that very high HDL-C levels increased cardiovascular death in women above 116 mg/dL (HR 1.47; 95% CI 1.01–2.15) and in men above 94 mg/dL (HR 1.29; 95% CI 1.01–1.65) (p_nonlinearity <0.01). These findings suggest that very high HDL-C levels are not protective against CV mortality and may, in fact, increase CV mortality risk especially in men. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Clinical Lipidology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)