Abstract 10710: Plasma Proteomic Profiles of the Blood Pressure Response During Exercise Are Associated With Incident Hypertension

Introduction: The blood pressure (BP) response during acute exercise (acute exercise blood pressure (AEBP)) is related to future risk of hypertension (HTN) and cardiovascular disease (CVD). Biochemical characterization of AEBP could identify novel biomarkers of CVD risk and inform understanding of its biology. Methods: We applied an aptamer-based proteomics platform to assay ~5000 proteins at rest in 681 healthy individuals of the HERITAGE Family Study (mean age 34y, 54% women) who underwent an acute exercise perturbation. AEBP was measured during submaximal exercise on a cycle ergometer. We then performed a proteomic association study of resting BP and AEBP. Top protein associations with acute exercise SBP and DBP were analyzed for their association with incident HTN and CVD in the Framingham Heart Study (FHS). Putative causal effects of AEBP-related proteins were investigated by Mendelian randomization (MR), using cis-protein quantitative loci genetic instruments. Results: We identified new markers of AEBP, many of which are secreted proteins that span biological processes relevant to vascular function including transforming-growth factor beta-receptor 3 (β = -3.39, p = 2.33e-6), prostaglandin D2-synthase (β = -2.50, p = 1.18e-10-9), and angiopoietin-related protein 4 (β = 2.44, p = 1.05e-4). The addition of 12 AEBP-associated proteins to clinical information informed future risk of HTN and CVD among normotensive community-dwelling individuals (clinical model, clinical proteomic model AUCs: incident HTN 0.69, 0.73; coronary heart disease 0.73, 0.76; heart failure 0.83, 0.87). MR analysis of AEBP-associated proteins supported a potential causal relationship between 5 proteins and BP regulation (TGFBR3, ANGPTL4, CGA FSHB, PTGDS, KLK8). Conclusions: We identified new blood biomarkers of BP regulation that were elicited only by an acute exercise perturbation and highlight novel potential causal pathways.