Abstract
Background: Nonalcoholic fatty liver disease (NAFLD) is associated with atherogenic dyslipidemia and an increased risk of cardiovascular events. Previous studies have suggested a paradoxical inverse relationship between NAFLD severity and Lp(a) level, an independent cardiovascular risk factor. However, contemporary data in patients with biopsy-proven NAFLD in the U.S. are lacking. Hypothesis: NAFLD severity on liver biopsy has a discordant association with Lp(a) and other markers of atherogenic dyslipidemia. Methods: Lp(a), traditional lipid profile, apolipoproteins, and nuclear magnetic resonance-based lipoprotein particle concentration were measured in 151 patients with NAFLD. Levels were compared between those with nonalcoholic fatty liver (NAFL) on histology and non-alcoholic steatohepatitis (NASH), the clinically aggressive NAFLD variant. Results: Median age was 55 [48, 62] years, 67% of patients were women, 83% were White, 43% had NAFL, and 57% had NASH. Demographic characteristics were similar among those with NAFL and NASH. Triglyceride level was higher and High-Density Lipoprotein-cholesterol (HDL-C) was lower among those with NASH as compared with NAFL. Circulating concentration of two key markers of atherogenic dyslipidemia, Apolipoprotein-B (apoB) and Low-Density Lipoprotein particle concentration (LDL-P) was 9% and 17% higher in the NASH group as compared with NAFL, respectively. Contrastingly, Lp(a) concentration was 50% lower in NASH relative to NAFL group (Figure). Hepatocyte ballooning, lobular inflammation, and fibrosis on histology were inversely associated with Lp(a) concentration, while steatosis severity was not. Conclusions: NAFLD severity has a discordant association with Lp(a) and markers of atherogenic dyslipidemia. The mechanistic basis of this relationship may have implications for prognosticating cardiovascular disease risk and determining the safety of targeted Lp(a) lowering in patients with NAFLD.
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