Abstract 18742: Matrilysin (MMP7) as a Robust Predictor of Hypertension Incidence and Complications: Findings From a Proteomic Analysis in the Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Introduction: Proteomic techniques can be applied for the discovery of common pathways underlying both incident hypertension and hypertension-related cardiovascular outcomes. Research Questions: To identify and validate proteins associated with incident hypertension and to examine the association of these validated proteins with hypertension-related cardiovascular events. Methods: We quantified the association of 4,955 plasma proteins (measured by SomaScan® Version 4 Assay) with incident hypertension (defined as systolic blood pressure (BP) ≥140, diastolic BP ≥ 90 mmHg, or hypertension medication use) in participants free of hypertension at ARIC visit 3 (1993-95) using Cox regression models adjusted for demographics, clinical characteristics and baseline BP. Significant associations were validated using proteomic measurements at ARIC visit 2 (1990-92). We then examined the association of validated proteins with incident coronary heart disease (CHD), stroke, and heart failure (HF) among participants with hypertension at visit 3 using Cox regression models additionally adjusted for hypertension duration and treatment. Results: There were 5,080 participants in the discovery cohort (mean age 59y, 13% Black, 54% women, median follow up 11 y) and 6,810 in the validation cohort (median follow up 3.1y). Four proteins were significantly associated with incident hypertension in the discovery cohort. One protein, Matrilysin (MMP7), remained significantly associated in the validation cohort (HR 1.22 [1.11-1.34]) (Figure1A). MMP7 was also significantly associated with all hypertension-related complications (Figure 1B-D). Conclusions: MMP7, a protein involved in extracellular matrix degradation, was robustly associated with incident hypertension and cardiovascular events. Future research examining the pathophysiologic mechanism of MMP7 could potentially yield drug targets for the prevention and treatment of hypertension.