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，强化治疗减少了全球CVD，同时增加了与临床相关的不良不良 效果。 Sprint试验结果的广泛应用和扩展将创造巨大 实际挑战。因此，迫切需要开发个性化和务实 BP治疗的方法，可以优化对个人的识别 从密集的BP治疗中获得最大的好处。反映中间体的生物标志物 疾病表型可能代表强大的工具来指导高血压治疗 与临床结果和广泛应用的可行性密切相关。事先的 文献表明高灵敏度心脏肌钙蛋白（HS-CTNT）和N末端Pro-BNP （NT-ProBNP）表征HF和CVD死亡率高风险的个体，临床 在Sprint中，强化BP控制的结果最为强大。除了基线 生物标志物水平，HS-CTNT或NTPROBNP的增加与增加的风险有关 心血管死亡率和心力衰竭，而这些标记的减少是相关的 事件速率较低。因此，这些观察结果表明这些生物标志物可能 确定值得更密集的BP目标的高风险个人，可能对 监视对BP降低的响应。因此，我们建议测量HS-CTNT和NT- 在Sprint试验中，基线，1年级和2年级的ProbNP以实现以下目的： 特定目标1：确定Sprint参与者是否患有早期心血管末端器官伤害 通过降低强化BP获得更大的好处（Sprint Primarts的减少减少 结果）;特定目标2：在短跑试验参与者中，确定密集型的影响 BP对HS-CTNT和NT-PROBNP的控制从基线到随访（1年级和2年）变化。这 这项研究的发现将有助于确定那些最有可能受益的人 BP控制，提供一种新颖，有效且廉价的个性化BP管理策略 可以广泛实施。