Abstract 15669: Proteomic Associations With Late-Life Cardiac Structure and Function: The Atherosclerosis Risk in Communities Study

Introduction: Alterations in cardiac structure and function underlie heart failure (HF). Identification of novel markers of cardiac function may provide insights into HF pathophysiology.

Methods: Among 4253 participants in ARIC who were free of HF and atrial fibrillation at study Visit 5 (2011-13) and had aptamer-based proteomics (SomaScan v4), we used exploratory factor analysis to reduce 21 echocardiographic measures (2D, spectral and tissue Doppler, strain) to 5 factors. We assessed the association of 4955 plasma proteins with each factor using multivariable linear regression. Hierarchical clustering grouped proteins associated with ≥1 factor by their pattern of association with the factors. Association of protein levels with incident HF post-Visit 5 was assessed using multivariable Cox models. Two-sample Mendelian randomization (MR) was performed to evaluate potential causal effects of proteins on HF and left/right ventricular (LV/RV) size & function.

Results: Mean age was 75±5 years, 41% were male, 17% reported Black race. We identified 5 factors representing: cardiac structure, LV myocardial motion, LV chamber level contractility, LV filling pressure, and RV myocardial motion. 409 proteins were significantly associated with ≥1 factor, 101 of which were significantly associated with HF. Hierarchical clustering grouped proteins into 6 clusters (Figure). The 54 proteins in Cluster 5 demonstrated consistent associations across all factors and were enriched for proteins associated with HF. MR identified 7 proteins, including CHST15 - a sulfotransferase involved in proinflammatory cytokine biosynthesis - which demonstrated potential causal effects on HF and on LV/RV volume.

Conclusion: We uncovered a subset of plasma proteins associated with multiple dimensions of cardiac structure and function and with HF risk. A subset, including CHST15, had potential causal effects on cardiac structure/function and HF and warrant further investigation.