Abstract 14976: Proteomic Measures Linking Social Determinants of Health to Heart Failure Risk: The Atherosclerosis Risk in Communities Study

Abstract

Introduction: Adverse social determinants of health (SDOH) are risk factors for heart failure (HF), and both disproportionately burden Black adults. The mechanisms linking SDOH to incident HF are unclear. Methods: Among 9910 HF-free participants in the community-based ARIC study with proteomic data (Somascan v4) at Visit 3 (V3; 1993-95), we performed race-stratified (Black and non-Black race) analyses of the association of 4955 plasma proteins with SDOH and incident HF. We derived a SDOH factor based on income, education level, and neighborhood area deprivation index using exploratory factor analysis. We evaluated cross-sectional associations of the SDOH factor with proteins using age- and gender- adjusted linear regression at Bonferroni significance. The association of SDOH-associated proteins with incident HF during 10 years post-V3 was assessed using Cox PH regression further adjusting for cardiovascular co-morbidities, using an FDR <0.05. Mendelian randomization analysis assessed for a possible causal effect on HF among candidate proteins common to both race groups. Results: Of 9910 participants, 1981 reported Black race (age 59±6 years; 60% female) and 7929 non-Black race (60±6; 52% female). The SDOH factor was associated with incident HF in both race strata (adjusted HR 1.29 [95% CI 1.07-1.54] and 1.38 [1.24-1.53] respectively). Among Black participants, 80 proteins associated with the SDOH factor, 52 of which associated with incident HF. Among non-Black participants, 866 proteins associated with the SDOH factor, 188 of which associated with incident HF. Twenty-two proteins were associated with SDOH and HF in both race groups (Figure). Mendelian randomization supported a possible causal effect of C1QTNF1, an inflammation-associated adiponectin paralog, on HF. Conclusions: Large scale proteomics identifies proteins potentially linking SDOH to HF risk. C1QTNF1 associates with SDOH burden, has a possible causal effect on HF, and warrants further study.