Abstract 14625: Association of Eicosanoid Metabolites With Cardiac Structure and Function

Introduction: Eicosanoids are bioactive lipids that govern the upstream initiation of pro- and anti-inflammatory activity. They may serve as important pathways by which obesity and cardiometabolic disease lead to the development of heart failure with preserved ejection fraction (HFpEF).

Objective: We sought to examine the association of plasma circulating eicosanoid metabolites with subclinical cardiac remodeling as ascertained by cardiac magnetic resonance imaging (CMR) as important determinants of HFpEF risk.

Methods: We studied 3880 MESA study participants (mean age 63±10 years, 53% women) who underwent plasma metabolite profiling using a mass spectrometry-based platform and CMR. We used multivariable linear regression to examine the association of eicosanoid metabolites with left ventricular mass index (LVMI, primary outcome), LV end-diastolic volume index (LVEDV), and left atrial volume (LAV).

Results: Of 811 eicosanoids, 158 were associated with LVMI (Figure; FDR q <0.05 for all). Specifically, derivatives of eicosadienoic acid (15 oxoEDE), linoleic acid (9,10 diHOME), and arachidonic acid (12(R) HETE) were negatively associated with LVMI and prostaglandin 19R-hydroxy-PGE1 was positively associated with LVMI. Of 158 metabolites, 65 were are also associated with LVEDV including derivatives of linoleic acid (13(S) HOTrE), oxylipin 11-HETE and 15 oxoEDE. Of 158 metabolites, Adrenic acid is also associated with LAV.

Conclusions: We found that specific eicosanoids including 15 oxoEDE, 9,10 diHOME, and 12(R) HETE were associated with LVMI, an important measure of subclinical cardiac remodeling and precursor to HFpEF. As causal drivers of HFpEF are poorly characterized, a better understanding of pro- and anti-inflammatory eicosanoid pathways that contribute to cardiac remodeling may have important implications for the prevention of HFpEF.