SPRINT - Heart

描述(由申请人提供)：左心室肥厚(LVH)非常常见，是主要心血管不良事件(CV)和死亡率的强烈独立预测因子，并具有很大的可归因性人群风险。左心室肥厚的消退可能会减少随后的心血管事件和死亡，可能独立于BP。然而，在将LVH初步确立为一个独立的治疗靶点之前，仍有几个关键问题，高血压治疗、LVH消退和减少心血管事件之间的关键联系还没有被很好地理解。即将到来的由NHLBI资助的Sprint研究是一个独特的、有时间限制的机会，可以高效和经济地解决这些重要问题。Sprint将是一项对照临床试验，以确定与标准对照(BP&lt；140 mm Hg)相比，密集降低收缩压至120 mm Hg是否会减少心血管事件。拟议的Sprint心脏辅助研究对RFA HL10-024高度响应，并创新性地整合了各种资源：最新的心血管磁共振成像(CMR)技术、5个非常适合的临床地点、新的干预措施和大型随机临床事件试验。它将从Sprint公司招募340名参与者(每组170人)，并在基线和18个月的随访中测量左室质量和舒张末容量(EDV)，以解决以下基本假设：假设：在18个月的随访中，强化降压组与标准对照组相比，左室质量减少，左室重构改善。这项研究还将在随访期间(平均3.4年)确定Sprint中LV质量和EDV与CV复合终点的关系，以检验以下第二假设：LV质量和重塑的改善将与CV事件的减少相关。作为一个探索性目标，强化降压组和标准对照组将测量从基线到18个月随访的左室应变、心肌纤维化、左房容量和主动脉僵硬的变化。这将使这项研究能够探索在Sprint测试的范围内密集降压影响LVH和CV事件的潜在机制。通过确定这些更新颖的CMR措施对密集降压的反应，它也将为它们在未来试验中的潜在纳入奠定基础。最后，这项研究将在特别感兴趣的人群中研究18个月来简历结构和功能的变化之间的关系，这些亚组包括既往患有心血管疾病的人、75岁的人和慢性肾脏疾病的人。SPRINT-HEART将测试原本无法解决的关键假设，挑战现有的范例，克服先前研究的局限性，提供关键的机制信息来帮助解释Sprint的结果，并促进我们对LVH及其管理与公共卫生的相关性的理解：左心室肥厚(LVH)在普通人群中很常见，是包括心脏病发作、心力衰竭和死亡在内的心血管(CV)事件的强烈独立预测因子。然而，预防或减少LVH所需的最佳血压控制(BP)水平尚不清楚，也不清楚应在多大程度上独立于BP而针对LVH。短跑心脏是一种创新且经济高效的方法，可以促进我们对BP治疗、心脏结构和功能以及心血管事件之间的机制联系的理解。(摘要结束)

DESCRIPTION (provided by applicant): Left ventricular hypertrophy (LVH) is very common, is a strong independent predictor of major adverse cardiovascular (CV) events and mortality, and has a large attributable population risk. Regression of LVH may reduce subsequent CV events and death, potentially independent of BP. However, several critical questions remain before LVH can be established as an independent therapeutic target primarily, and the critical links between hypertension treatment, LVH regression, and reduction in CV events are not well understood. The upcoming, NHLBI-funded SPRINT study is a unique, time-limited opportunity to efficiently and cost-effectively address these important questions. SPRINT will be a controlled clinical trial to determine whether intensively reducing systolic BP to <120 mmHg will reduce CV events compared to standard control (BP <140 mmHg). The proposed SPRINT-HEART ancillary study is highly responsive to RFA HL10-024 and innovatively assembles an ideal combination of resources: the latest cardiovascular magnetic resonance imaging (CMR) techniques, 5 well-suited clinic sites, a novel intervention, and a large randomized clinical events trial. It will enroll 340 participants from SPRINT (170 each group) and measure LV mass and enddiastolic volume (EDV) at baseline and at 18-month follow-up to address the following primary hypothesis: Hypothesis: At 18-month follow-up the intensive BP reduction group will have reduced LV mass and improved LV remodeling compared to standard control. The study will also determine the relationship of LV mass and EDV with the CV composite endpoint in SPRINT during follow-up (mean 3.4 years) to examine the following secondary hypothesis: The improvements in LV mass and remodeling will be associated with reductions in CV events. As an exploratory aim, the change frombaseline to 18-month follow-up in LV strain, myocardial fibrosis, left atrial volume, and aortic stiffness will be measured in the intensive BP reduction and standard control groups. This will enable the study to explore potential mechanisms whereby intensive BP reduction, in the range being tested in SPRINT, influences LVH and CV events. By determining the responses of these more novel CMR measures to intensive BP reduction, it will also lay the groundwork for their potential inclusion in future trials. Finally, the study will examine the relationships between the 18-month changes in CV structure and function in subgroups of particular interest including those with prior CV disease; those > 75 years old, and those with chronic kidney disease. SPRINT-HEART will test critical hypotheses that would not otherwise be addressable, challenge existing paradigms, overcome limitations of prior studies, provide key mechanistic information to help interpret the SPRINT results, and advance our understanding of LVH and its management PUBLIC HEALTH RELEVANCE: Left ventricular hypertropy (LVH) is common in the general population and is a strong independent predictor of cardiovascular (CV) events, including heart attack, heart failure, and death. However, the optimal level of blood pressure control (BP) needed to prevent or reduce LVH is unknown, and the extent to which LVH should be targeted independently of BP is not clear. SPRINT-HEART is an innovative and cost-effective approach to advance our understanding of the mechanistic links between BP treatment, cardiac structure and function, and CV events. (End of Abstract)