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Grant Abstract: Metabolic Pathways Underlying the Contrasting Sodium-BP and DASH/OmniHeart-BP Relationships

Grant Number: 5R01HL135486-02
PI Name: Van Horn
Project Title: Metabolic Pathways Underlying the Contrasting Sodium-BP and DASH/OmniHeart-BP Relationships

Abstract: The GENERAL AIM of this supplemental proposal is to qualitatively advance knowledge specifically related to magnesium (Mg) and also calcium(Ca) intake as part of overall research on urinary metabolic phenotypes and biochemical pathways associated with direct effects of high sodium (Na) and inverse effects of the DASH/OmniHeart-like eating patterns on blood pressure (BP). To achieve this aim, we will identify and quantify key metabolites with a focus on those related to MG and Ca intake, as related to these contrasting BP influences, and use state-of-the-art chemometrics, statistical spectroscopy, computational network and pathway modelling tools to identify and map de novo pathways associated with Na-BP and DASH/OmniHeart-BP. We will then test and validate the INTERMAP derived metabolites and pathways using available data and samples from the INTERMAP China Prospective (ICP) Study, the Urinary Sodium Study (USS), and the OmniHeart Trial. The goal is to develop more focused and effective strategies for population-wide BP lowering through improved non-pharmacologic approaches, primarily nutritional involving dietary Mg and Ca intakes, and identify potential new targets for supplement and/or drug intervention. To our knowledge, this is the first investigation to identify urinary metabolites and associated pathways related to Na-BP and DASH/OmniHeart-BP, link these to dietary data specifically on Mg and Ca intake, with diet and urinary validation in other cohorts, prospective and trial data.

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