Abstract P537: Plasma Proteins Partially Explain the Independent Associations of Obesity With Ventricular Hypertrophy and Diastolic Dysfunction in Older Adults Without Cardiovascular Disease

Background: Obesity is associated with excess heart failure (HF) risk that is not explained by traditional cardiovascular risk factors. Prior proteomic analyses of middle-aged adults with obesity have identified a set of proteins that may significantly mediate the risk of obesity-associated HF. The mediating effect of these proteins on subclinical cardiac dysfunction in obesity is unclear. Methods: We conducted a cross-sectional analysis of ARIC Visit 5 (2011-13) participants free of HF and coronary heart disease. We measured 4 plasma proteins positively associated with obesity and HF (ANGPT2, COL28A1, GABARAP, GABARAPL1) and 5 proteins negatively associated with obesity and HF (ART3, EGFR, EPHA4, OMG, SEZ6L) using SOMAScan v4.0. We used linear regression to evaluate the adjusted associations of obesity with echocardiographic parameters and the extent of attenuation after adjustment for these plasma proteins. Results: We included 3,244 participants (mean age 75 years, 61% female, 16% Black, 31% with obesity). Individuals with obesity had worse diastolic function and greater ventricular hypertrophy. After adjustment for cardiovascular risk factors, those with obesity still had higher left ventricular (LV) mass index (ß: 3.64, 95%CI: 2.29, 5.00), left atrial (LA) anteroposterior diameter (ß: 0.27, 95%CI: 0.23, 0.30), LA volume index (ß: 1.41, 95%CI: 0.75, 2.06), and lateral E/e’ ratio (0.55, 95%CI: 0.27, 0.82). After adjustment for all 9 plasma proteins, associations were attenuated for LV mass index, LA anteroposterior diameter, and lateral E/e’ ratio (36%, 26%, 22% attenuation, respectively) and the association with LA volume index was no longer significant. Conclusion: Proteins associated with HF risk in obesity explain some of the associations of obesity with diastolic dysfunction and ventricular hypertrophy, above and beyond traditional risk factors. These proteins should be investigated to further elucidate and potentially mitigate the development of cardiac dysfunction among individuals with obesity.