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

摘要 最近，SPRINT试验表明，与标准血压相比， 强化治疗降低了总体CVD，同时增加了临床相关不良反应。 方面的影响. SPRINT试验结果的广泛应用和推广将创造巨大的 实际挑战。因此，迫切需要开发个性化和实用的 BP治疗的方法，将优化识别个人， 从密集的BP治疗中获得最大的益处。反映中间体的生物标志物 疾病表型可能是指导高血压治疗的有力工具， 与临床结果和广泛应用的可行性的强关联。之前 文献表明，高敏心肌肌钙蛋白（hs-cTnT）和N-末端-pro-BNP （NT-proBNP）表征HF和CVD死亡率高风险的个体， 在SPRINT中，强化BP控制最有力地降低了结局。除了基线 生物标志物水平，hs-cTnT或NTproBNP升高与以下风险增加相关： 心血管死亡率和心力衰竭，而这些标志物的减少与 事件发生率较低。因此，这些观察结果表明，这些生物标志物可能 识别高风险个体，他们值得更密集的BP目标，并可能有助于 监测对BP降低的反应。因此，我们建议测量hs-cTnT和NT- SPRINT试验中基线、第1年和第2年的proBNP，以实现以下目标： 具体目标1：确定SPRINT参与者是否存在早期心血管终末器官损伤 从强化降压中获得更大的获益（SPRINT原发性高血压 具体目标2：在SPRINT试验参与者中，确定强化 hs-cTnT和NT-proBNP从基线到随访（第1年和第2年）的血压控制变化。的 这项研究的结果将有助于确定那些最有可能从密集的 BP控制，提供一种新颖、有效、廉价的个性化BP管理策略 可以广泛实施。

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.