Cholesterol efflux capacity is impaired in subjects with an elevated Fatty Liver Index, a proxy of non-alcoholic fatty liver disease

Abstract

Background and aims: Non-alcoholic fatty liver disease (NAFLD) parallels the obesity epidemic and associates with components of the metabolic syndrome (MetS). Cholesterol efflux capacity (CEC) represents a key metric of high density lipoprotein (HDL) function which may predict atherosclerotic cardiovascular disease (CVD). Here we assessed the relationship of CEC with NAFLD.

Methods: CEC was determined from THP-1 macrophage foam cells towards apolipoprotein B-depleted plasma among 639 subjects (454 men; 36 subjects with type 2 diabetes mellitus (T2D); 226 with MetS), participating in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. A Fatty Liver Index (FLI) ≥ 60 was used as a proxy of NAFLD.

Results: 372 participants had a FLI ≥60, which coincided with an increased prevalence of T2D and MetS (p = 0.009 and p < 0.001), as well as with central obesity, higher systolic blood pressure, glucose, total cholesterol, triglycerides and high sensitivity C-reactive protein (hsCRP), and decreased HDL cholesterol (p < 0.001 for each). In multivariable linear regression analyses, CEC was inversely associated with an elevated FLI, when taking account of clinical covariates (fully adjusted model: β = -0.091, p = 0.043), and alternatively when taking account of systolic blood pressure, waist/hip ratio, glucose, HDL cholesterol, triglycerides and hsCRP (fully adjusted model: β = -0.103, p = 0.034).

Conclusions: Impaired CEC is associated with NAFLD, as inferred from a FLI≥60, even when taking account of lower HDL cholesterol and enhanced low-grade chronic inflammation. Reduced CEC could contribute to accelerated CVD in NAFLD patients.

Keywords: Cholesterol efflux capacity; Fatty Liver Index; HDL cholesterol; Metabolic syndrome; Non-alcoholic fatty liver disease; Type 2 diabetes mellitus; hsCRP.