Biomarkers of myocardial injury, blood pressure and cardiovascular outcomes in SPRINT

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Abstract Recently, the SPRINT trial demonstrated that compared with standard blood pressure treatment, intensive treatment reduced global CVD while increasing clinically-relevant adverse effects. Broad application and extension of the SPRINT trial results will create enormous practical challenges. Thus, there is a critical need to develop personalized and pragmatic approaches to BP treatment that would optimize the identification of individuals that would receive the greatest benefit from intensive BP treatment. Biomarkers that reflect intermediate disease phenotypes may represent powerful tools to guide hypertension treatment given their strong association with clinical outcomes and the feasibility of widespread application. Prior literature suggests that both high sensitivity cardiac troponin (hs-cTnT) and N-terminal-pro-BNP (NT-proBNP) characterize individuals at high risk for both HF and CVD mortality, the clinical outcomes most robustly reduced by intensive BP control in SPRINT. In addition to baseline biomarker levels, increases in hs-cTnT or NTproBNP are associated with increased risk for cardiovascular mortality and heart failure, whereas decreases in these markers are associated with lower event rates. Therefore, these observations suggest that these biomarkers may identify high-risk individuals who merit more intensive BP goals and may be useful for monitoring the response to BP lowering. Therefore, we propose to measure hs-cTnT and NT- proBNP at baseline, year 1, and year 2 in the SPRINT trial to accomplish the following aims: Specific Aim 1: Determine if SPRINT participants with early cardiovascular end organ damage derive greater benefit from intensive BP lowering (augmented reduction in SPRINT primary outcome); Specific Aim 2: Among SPRINT trial participants, determine the impact of intensive BP control on hs-cTnT and NT-proBNP changes from baseline to follow-up (year 1 & 2). The findings from this research will help identify those individuals most likely to benefit from intensive BP control, providing a novel, effective, and inexpensive personalized BP management strategy that can be implemented broadly.