The Role of the Alms1 Gene in the Development of Salt-Sensitive Hypertension

Wayne State University, Detroit MI

Investigators

Abstract

DESCRIPTION (provided by applicant): Resistant hypertension (RH) is an exquisitely salt-responsive blood pressure (BP) phenotype that affects approximately 7- 9 million adults in the U.S. which is increasing in prevalence and has been linked to higher cardiovascular-renal risk than non-RH. This research is focused on identifying both the hemodynamic determinants and salt-responsive biomarkers of RH that will identify hypertensive individuals likely to develop RH. The hemodynamic determinant(s) of RH is not known and there are no known biomarkers (which are more readily available tests than hemodynamic measurements) of RH as well. Impedance cardiography (ICG) will be used to make non-invasive determinations of the hemodynamic variables which determine BP. We have previously shown that systemic vascular resistance (SVR) is significantly greater and the total arterial compliance index (TACI) is much lower in RH than in non-RH. The rationale for examining salt-responsive biomarkers is the following: 1) reducing dietary sodium intake will quickly and impressively lower BP in persons with RH, 2) the SVR and TACI (i.e. arterial stiffness) are both worsened by augmenting dietary sodium intake, 3) the chosen biomarkers, asymmetric dimethylarginine (ADMA) and dimethylarginine dimethylaminohydrolase (DDAH) are both salt-responsive. The specific aims of my proposed research are: 1) to identify (derivation cohort) and validate (validation cohort) the hemodynamic (SVR and TACI) determinants of RH; 2) to determine the relative ability of these hemodynamic determinants to discriminate between hypertensive individuals who will and will not develop RH (validation cohort), and 3) to determine if salt-responsive biomarkers (ADMA, DDAH and ADMA:DDAH ratio) discriminate between hypertensive individuals who will and will not develop RH (the newly recruited subgroup of validation cohort) and, if so, to directly contrast the discrimination of the best salt-responsive biomarker with the best hemodynamic determinant.