Greater capacities in 3 key measures of high-density lipoprotein (HDL) functionality were found to be associated with a reduced risk for cardiovascular disease (CVD), according to study results published in Atherosclerosis.

It remains unclear whether the cardioprotective effect of HDL-cholesterol is due to its lipoprotein or cholesterol component.

With this systematic review and meta-analysis conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement, investigators sought to synthesize information from all applicable observational studies that assessed the relationship between HDL function and CVD and mortality risks. The Medline and Embase databases were queried through April 2019, for studies in which the functionality of isolated HDL (without the cholesterol component) was assessed and in which major adverse CV events or mortality were outcomes. A total of 29 manuscripts were identified for inclusion in the review.

Among the included studies, cholesterol efflux capacity (CEC) was examined in 20 studies (n=21,022; 47.8% men), of which 7 were cross-sectional and 13 were prospective in design. There were 10 studies (n=2563; 66.2% men) in which HDL antioxidant capacity was examined (3 cross-sectional and 7 prospective designs), and 2 studies in which the anti-inflammatory capacity of HDL was examined (1 cross-sectional; 1 prospective).


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Based on 8 comparable prospective investigations, an association was established between greater CEC and reduced CVD risk (relative risk [RR] per 1 standard deviation increase, 0.86; 95% CI, 0.76-0.98; P =.002). In addition, 5 studies revealed an association between greater CEC and lower risk for mortality (RR, 0.77; 95% CI, 0.60-1.00).

In 2 studies, a nonsignificant trend between increased HDL antioxidant capacity and reduced CVD risk was observed (pooled RR, 0.70; 95% CI, 0.32-1.53; P =.004), and a significant relationship with mortality was observed in 3 reports (pooled RR, 0.48; 95% CI, 0.28-0.81).

In the only prospective study included in the analysis (n=204; 67% men), HDL anti-inflammatory activity was associated with a reduced CVD risk. The small number of studies included precluded a meta-analysis.

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Study limitations include the inclusion of broad outcomes, inability to examine the effects of HDL on various clinical manifestations, varied baseline characteristics across studies, and variations in experimental approaches.

“The present systematic review and meta-analysis represents a valuable comprehensive summary of the state-of-the-art regarding HDL functionality and its utility as predictor of cardiovascular diseases and mortality,” noted the authors.

Reference

Soria-Florido MT, Schröder H, Grau M, Fitó M, Lassale C. High density lipoprotein functionality and cardiovascular events and mortality: A systematic review and meta-analysis. Atherosclerosis. April 2020. doi:10.1016/j.atherosclerosis.2020.04.015