Abstract 9691: Lipoprotein Subclasses Are Associated With Hepatic Steatosis: Insights from the Prospective Multicenter Imaging Study for the Evaluation of Chest Pain (PROMISE) Clinical Trial

Abstract

Introduction: Hepatic steatosis (HS) is associated with coronary artery disease (CAD) and cardiovascular (CV) events. Previously, we have demonstrated that granular measures of lipids (lipoprotein particle number/size) are associated with CAD and CV events and incremental to traditional lipid measures. Hypothesis: Granular measures of lipids are associated with HS detected by cardiac computed tomography (CT) and with HS detected by histopathology. Methods: We included 1524 subjects from the PROMISE trial. HS was defined as CT attenuation of the liver <40HU or liver<spleen HU on CT. Plasma lipoprotein particle parameters were measured by NMR. Principal components analysis was used for dimensionality reduction and logistic regression was used to test the association of lipoprotein factors and individual lipoproteins with HS cases and controls in uni/multivariable models. The association of lipoproteins with HS was validated in an independent cohort of 58 subjects (Laval U) with and without HS defined by histopathology on liver biopsy. Results: Subjects with HS (n=413) were slightly younger (59±8 vs 61±8 yrs) and more likely men (53 vs 44%) as compared to controls (n=1111). Three lipoprotein factors were associated with HS: LDL/LDL particle size (OR 1.36, 95%CI 1.21-1.53, p<0.001); HDL/HDL size (OR 1.75, 95%CI, 1.53-2.02, p<0.001), and TG-rich-lipoprotein particles (OR 0.74, 95% CI 0.65-0.84, p<0.002). Individual lipoproteins heavily loaded in these factors were also significant in multivariable analysis (Figure). These lipoproteins were also associated with HS in the validation cohort: small LDL (OR 6.36, p<0.05), large HDL (OR 0.29, p<0.05), and large TG particles (OR 13.83, p<0.05). Conclusions: We found association of small LDL, large HDL and large TG particles, previously associated with CV event risk, with HS phenotyped by CT and histopathology. These results suggest that use of lipoprotein subclasses may improve CV risk assessment in patients with HS.