Abstract 17081: Targeted Proteomics Identifies Circulating Biomarkers Associated With Biological Sex in Dilated Cardiomyopathy

Abstract

Background: The pathophysiology underlying sex specific differences in dilated cardiomyopathy (DCM) is incompletely understood. Targeted proteomic discovery enables quantification of low abundance circulating proteins to elucidate mechanisms of disease. Hypothesis: Female sex is associated with a distinct biomarker profile that confers insights into DCM pathogenesis. Aim: Evaluate the biomarker profile associated with biological sex in dilated cardiomyopathy. Methods: Cross sectional analysis of 490 patients with dilated cardiomyopathy confirmed by cardiovascular magnetic resonance imaging. Targeted proteomic analysis was performed with proximity extension assays to determine sex differential expression of 276 proteins associated with inflammation or cardiovascular disease. Expression was compared between males and females. Results: A third of patients were female (n=160, 33%). After adjusting for false discovery, 10 proteins were significantly upregulated and 8 were significantly downregulated in female compared to male patients (A Inflammatory panel, B Cardiovascular panel). These were grouped into 3 clusters (C), enriched for cytokine pathways (red), regulators of cardiac function (green), and markers of fat metabolism (blue). Of the sex differentially expressed proteins, GDF2 (regulates angiogenesis), protein BOC (augments cardiac tissue repair) and CD5 (linked to inflammation) were top determinants of biological sex after adjusting for age, renal function, body mass, and cardiac function (D). Conclusion: Sex specific proteomic signatures provide new insights into the pathophysiology underlying sex differences in DCM. Figure: Volcano plots showing log2 fold change in protein expression in inflammatory (A) and cardiovascular (B) proteins. Blue = lower and red = higher levels in females. Protein interactions shown in C. Top predictive feature of sex is body surface area, followed by biomarkers GDF2 and Protein BOC, shown in D.