SPRINT - Heart

描述（由申请人提供）：左心室肥大（LVH）非常常见，是重大心血管不良事件（CV）和死亡率的强独立预测因子，具有较大的归因人群风险。LVH的消退可能会减少随后的CV事件和死亡，可能与BP无关。然而，在LVH可以被确立为一个独立的治疗靶点之前，仍然存在一些关键问题，并且高血压治疗、LVH消退和CV事件减少之间的关键联系尚未得到很好的理解。即将到来的，NHLBI资助的SPRINT研究是一个独特的，时间有限的机会，以有效和具有成本效益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 <140 mmHg）相比，将收缩压降低至<120 mmHg是否会减少CV事件。拟定的SPRINT-HEART辅助研究对RFA HL 10 -024具有高度响应性，并创新性地组合了理想的资源组合：最新的心血管磁共振成像（CMR）技术、5个非常合适的临床研究中心、一种新型干预措施和一项大型随机临床事件试验。它将从SPRINT招募340名参与者（每组170名），并在基线和18个月随访时测量LV质量和舒张末期容积（EDV），以解决以下主要假设：假设：在18个月随访时，与标准对照组相比，强化降压组的LV质量降低，LV重塑改善。本研究还将确定随访期间（平均3.4年）SPRINT中LV质量和EDV与CV复合终点的关系，以检验以下次要假设：LV质量和重塑的改善将与CV事件减少相关。作为探索性目的，将测量强化降压组和标准对照组从基线到18个月随访时左心室应变、心肌纤维化、左心房容积和主动脉僵硬度的变化。这将使研究能够探索在SPRINT中测试的范围内强化BP降低影响LVH和CV事件的潜在机制。通过确定这些更新颖的CMR措施对强化BP降低的反应，它也将为它们在未来试验中的潜在纳入奠定基础。最后，该研究将检查特别关注的亚组中CV结构和功能的18个月变化之间的关系，包括既往CV疾病患者;> 75岁患者和慢性肾脏疾病患者。SPRINT-HEART将测试那些无法解决的关键假设，挑战现有的范式，克服先前研究的局限性，提供关键的机制信息以帮助解释SPRINT结果，并促进我们对LVH及其管理的理解

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