Association between extremely high-density lipoprotein cholesterol and adverse cardiovascular outcomes: a systematic review and meta-analysis.

Background: The association between high-density lipoprotein cholesterol (HDL-C) and adverse cardiovascular outcomes is understudied. Based on cohort studies, the current study aimed to investigate the association of extremely high HDL-C with all-cause, atherosclerotic cardiovascular disease (CVD) mortality, and stroke risk. Methods: A systematic literature search in Embase, PubMed, Cochrane Library, and Web of Science was performed to collect relevant cohort studies published before August 20, 2022. A random-effects model was used to pool relative risks (RRs) and 95% confidence intervals (CIs). Results: A total of 17 cohort studies involving 19,630,829 participants were included, encompassing 18,547,132 total deaths (1,328,036 CVD deaths). All-cause mortality, CVD mortality, and stroke risk in the extremely high HDL-C group were increased by 15% (RR = 1.15, 95% CI:1.05-1.25), 14% (RR = 1.14, 95% CI:0.96-1.35) and 14% (RR = 1.14, 95% CI:0.82-1.58), compared to the normal HDL-C group. In subgroup analyses, extremely high HDL-C was associated with a reduced risk of CVD mortality in women and a lower risk of stroke in men compared to normal HDL-C levels. Conclusions: The extremely high levels of HDL-C were associated with elevated risks of all-cause mortality, CVD mortality, and stroke. More well-designed studies are needed to confirm our findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=370201, identifier: CRD42022370201.