Abstract P202: Proteomic Markers Associated With the Risk of Incident Hypertension in the Community: The Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Introduction: Proteins are involved in the pathophysiology of hypertension (HTN), but there are no large scale prospective proteomic analyses of incident HTN. Hypothesis: To identify and validate plasma proteins associated with incident HTN among a bi-racial cohort in the US. Methods: We quantified the associations of 4,955 plasma proteins (measured by SomaScan version 4 assay) with incident HTN over median follow-up of 11 years among 5,080 participants without baseline hypertension at ARIC visit 3 (1993-95). We then validated significant proteins from the primary analysis with incident HTN between visit 2 (n=6,810 during 1990-92) and visit 3 (median follow-up of 3.1y), to avoid including the same incident HTN cases in both analyses. Incident HTN was defined as systolic blood pressure (BP) ≥140, diastolic BP ≥90 mmHg, or HTN medication use. We ran multivariable Cox models and applied Benjamin-Hochberg procedure, with false discovery rate of 0.05, to account for multiple comparisons. Results: In the primary analysis with visit 3 as baseline (mean age 59y, 54% women, 13% Black), 3,828 participants (75%) developed HTN, and we found 55 proteins significantly associated with incident HTN. Among them, 14 proteins were validated using visit 2 data (Figure). Of those, 11 showed positive associations with HTN, and they are involved in glycoprotein degradation (e.g., MMP7, HTRA1, ASGR1, GUSB, CPM), cell adhesion (e.g., LGALS3BP and RET), and inflammation (e.g., CRP). In contrast, 3 proteins, renin ([REN]), netrin receptor ([UNC5D] apoptosis) and secretogranin-3([SCG3] endothelial cell growth), had inverse relationships with incident HTN. Further exploration showed a U-shaped association between renin and incident HTN. Conclusion: We identified several proteins associated with incident HTN, with plausible functions contributing to the development of HTN. These findings have implications on understanding mechanisms of HTN and potential targets for prevention and treatment.