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

Abstract

BackgroundThe 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.MethodsA 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).ResultsA 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.ConclusionsThe 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 Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=370201, identifier: CRD42022370201.