High blood pressure (BP) is pervasive among US adults. Dietary interventions represent a critical strategy for the primary prevention of cardiovascular disease (CVD) among adults with elevated BP and hypertension (HTN). The presumed efficacy of dietary interventions for CVD prevention is grounded in two key pieces of evidence. First, short-term, controlled feeding studies show that complete replacement of a typical American diet with a healthful diet, i.e. the Dietary Approaches to Stop Hypertension (DASH) diet along with sodium reduction, significantly lowers BP. Second, long-term observational studies have consistently demonstrated a strong, dose-response relationship between BP and risk of CVD events. However, it remains unproven whether diet can mitigate ongoing cardiac damage. In fact, no clinical trial of the effects of the DASH diet and sodium reduction on CVD has ever been performed due to the cost, size, and duration needed to administer controlled DASH meals and observe CVD events. Over the past decade two biomarkers have emerged with substantial utility as (1) measures of contemporaneous, subclinical cardiac damage and (2) prognostic indicators, strongly predictive of CVD: high sensitivity troponins (hs-trp) and N-terminal pro b- type natriuretic peptide (NT-proBNP). These markers are powerful surrogates of CVD, affording a unique opportunity to use specimens from the original DASH and DASH-Sodium trials (preserved by the NHLBI Biorepository), and definitively answer whether short-term changes in diet can reverse subclinical cardiac damage. The investigative team of this proposal is well-positioned to execute this significant and innovative research plan. Dr. Juraschek has published extensively with the DASH-Sodium data, works closely with the original PI of these trials (Dr. Appel, a project collaborator), and has interacted with the NHLBI Biorepository on four distinct proposals (4 data or specimen requests), all of which are actively contributing toward new scientific publications. Dr. Christenson is a renowned expert in clinical laboratory science and hs-trp assessments, directing a state-of-the art laboratory that is able to measure these biomarkers in trivial amounts of serum. Furthermore, his ongoing partnerships with industry afford the opportunity to perform cost-efficient assays. Finally, Drs. Juraschek, Appel, and Christenson have worked together on a similar study involving NHLBI Biorepository specimens, demonstrating feasibility and informing the present proposal. In summary, this proposal will answer critical questions about the short-term effects of diet on subclinical cardiac injury and wall strain by applying recent advances in CVD biomarkers to existing, well-designed dietary trials from a team with a (1) proven track record of working with the NHLBI Biorepository, (2) intimate knowledge of nuances in the trials? design and analysis, and (3) international expertise in the measurement of the proposed markers from this proposal.
In two landmark NIH studies, both the Dietary Approaches to Stop Hypertension (DASH) diet and sodium reduction have been shown to lower blood pressure (BP) in adults at risk for cardiovascular disease (CVD) within a 3-month period. However, whether these short-term reductions in BP reduce concurrent, subclinical cardiac damage is unknown. Using stored serum from these trials maintained by the NHLBI Biorepository, we aim to measure high sensitivity troponin I (a marker of subclinical cardiac injury) and NT-proBNP (a marker of cardiac wall strain), to determine whether the DASH diet or sodium reduction can reverse short-term subclinical cardiac injury or dysfunction.