High density lipoprotein functionality and cardiovascular events and mortality: A systematic review and meta-analysis

Background and aims The aim of this systematic review and meta-analysis is to synthesize studies assessing the associations between high-density lipoprotein functionality and risk of cardiovascular disease and mortality. Methods We searched Medline and Embase for the identification of observational studies meeting the inclusion criteria. This meta-analysis was conducted following the PRISMA statement and was registered in PROSPERO (CRD42017065857). We pooled risk estimates with a random-effect model separately for cardiovascular disease (fatal and non-fatal) and all-cause mortality. Results Out of 29 manuscripts, 20 articles investigated cholesterol efflux capacity (13 prospective and 7 cross-sectional), 10 antioxidant capacity (7 prospective and 3 cross-sectional) and two anti-inflammatory capacity of high-density lipoprotein (1 prospective and 1 cross-sectional). A greater cholesterol efflux capacity was associated with lower risk of cardiovascular disease in 8 studies (RR for 1SD increase: 0.86; 95% CI: 0.76–0.98) and of mortality in 5 studies (RR for 1SD increase: 0,77; 0.60–1.00). Better antioxidant capacity was non-significantly associated with lower cardiovascular disease risk in 2 studies (RR for 1SD increase 0.70; 0.32–1.53) and significantly with mortality in 3 studies (RR for 1SD increase 0.48; 0.28–0.81). High-density lipoprotein anti-inflammatory ability was associated with a lower cardiovascular disease risk in the only prospective study. Conclusions Greater high-density lipoprotein cholesterol efflux capacity and antioxidant/anti-inflammatory capacities were associated with lower risk of cardiovascular disease. However, the heterogeneity between studies and evidence of publication bias warrants caution and highlights the need for larger prospective studies with standardized assays and specific outcomes.