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

SPRINT 中心肌损伤、血压和心血管结局的生物标志物

• 批准号: 9759983
• 负责人: Jarett D Berry
• 金额: $ 53.62万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9759983
• 关键词: Address; Adult; Adverse effects; Advocate; Biological Markers; Biomedical Research; Blood Pressure; Cardiac; Cardiovascular system; Caring; Chronic; Clinical; Data; Disease Management; Event; General Population; Goals; Health Care Costs; Health Policy; Heart Injuries; Heart failure; High Prevalence; Home environment; Hypertension; Individual; Injury; Link; Literature; Measures; Mediating; Medical; Medical center; Monitor; Myocardial; Organ; Outcome; Participant; Population; Precision Medicine Initiative; Public Health; Research; Risk; Stress; Target Populations; Therapeutic Intervention; Troponin; Work; base; blood pressure regulation; cardiovascular risk factor; clinically relevant; disease phenotype; disorder prevention; follow-up; health application; high risk; hypertension control; hypertension treatment; improved; innovation; interest; mortality; novel; patient oriented; personalized medicine; population health; precision medicine; primary outcome; pro-brain natriuretic peptide (1-76); response; tool; treatment as usual; treatment strategy

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.

抽象的 最近，SPRINT 试验表明，与标准血压相比 治疗、强化治疗减少了总体CVD，同时增加了临床相关不良反应 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、务实的 BP 治疗方法将优化个体识别 从强化血压治疗中获得最大益处。反映中间体的生物标志物 鉴于其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密切相关。事先的 文献表明，高敏心肌肌钙蛋白 (hs-cTnT) 和 N-末端-BNP 前体 (NT-proBNP) 表征了心力衰竭和心血管疾病死亡率高风险的个体，临床 SPRINT 中强化血压控制可最大程度地降低结果。除了基线 生物标志物水平、hs-cTnT 或 NTproBNP 的增加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 识别值得更深入的血压目标的高风险个体，并且可能对以下方面有用： 监测对血压降低的反应。因此，我们建议测量 hs-cTnT 和 NT- SPRINT 试验中的基线、第一年和第二年的 proBNP 旨在实现以下目标： 具体目标 1：确定 SPRINT 参与者是否患有早期心血管终末器官损伤 从强化降压中获得更大益处（SPRINT 初级降压的增强降压） 结果）;具体目标 2：在 SPRINT 试验参与者中，确定强化训练的影响 hs-cTnT 和 NT-proBNP 的血压控制从基线到随访（第 1 年和第 2 年）发生变化。这 这项研究的结果将有助于确定那些最有可能从强化训练中受益的人 血压控制，提供新颖、有效、廉价的个性化血压管理策略 可以广泛实施。