Discovery, Replication, and Validation of Biomarkers of the DASH Diet and Hypertension

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ABSTRACT Diet is a modifiable risk factor for one of the most serious threats to global public health: cardiovascular disease. The Dietary Approaches to Stop Hypertension (DASH) dietary pattern is one example of a high- quality diet that is high in fruits, vegetables, and low-fat dairy products and low in sodium, saturated fat, and cholesterol. The DASH diet is widely recognized as an effective approach for the prevention of hypertension, cardiovascular disease, and related cardiometabolic diseases. Existing biomarkers of dietary intake are few and represent single nutrients rather than a holistic dietary pattern. Metabolomics and proteomics are high- throughput methods for efficient measurement of compounds in biological specimens. The metabolome reflects the breakdown products of food that is consumed and can represent not only food items and their components but also dietary patterns. The proteome represents biological function and activity, which complements the metabolomic profile. We propose to conduct untargeted metabolomics and proteomics for the discovery of novel biomarkers of the DASH diet as well as biomarkers of DASH diet mediated blood pressure reduction. Findings will be replicated in two independent study populations and validated by using targeted, quantitative assays of candidate biomarkers. This cost-effective proposal leverages the existence of study data and biospecimens in the NHBLI BioLINCC repository as well as existing omics data. The study team is led by a K01-funded, early stage investigator who has been trained in metabolomics of diet and chronic disease outcomes. Study team members are established, senior investigators who have a history of collaboration with the Principal Investigator and complementary expertise in nutritional biochemistry, untargeted metabolomics and proteomics platforms, laboratory methodology, biostatistics, dietary intake, blood pressure, and deep knowledge of the study populations to be investigated. This proposed research will advance the current methods for assessing dietary intake and will provide insights for clinically-important, diet- modifiable metabolic pathways.