Quantitative Proteomic Analysis of Diabetes Mellitus in Heart Failure With Preserved Ejection Fraction

JACC Basic Transl Sci. 2021 Feb 10;6(2):89-99. doi: 10.1016/j.jacbts.2020.11.011. eCollection 2021 Feb.

Abstract

Diabetes mellitus (DM) is associated with a higher risk of heart failure hospitalization and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Using SomaScan assays and proteomics analysis of plasma from participants in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial and the Penn Heart Failure Study, this study identified 10 proteins with significantly different expression in patients with HFpEF and DM. Of these, apolipoprotein M was found to mediate 72% (95% CI: 36% to 100%; p < 0.001) of the association between DM and the risk of cardiovascular death, aborted cardiac arrest, and heart failure hospitalization.

Keywords: ApoM, apolipoprotein M; CI, confidence interval; CILP2, cartilage intermediate layer protein 2; DM, diabetes mellitus; HFpEF, heart failure with preserved ejection fraction; HR, hazard ratio; LASSO, least absolute shrinkage and selection operator; apolipoprotein M; diabetes; heart failure; mediation analysis; proteomics.