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和死亡率的一个强有力的独立预测因子，具有很大的可归因人群风险。LVH的消退可能减少随后的CV事件和死亡，可能与血压无关。然而，在将LVH确定为独立的主要治疗靶点之前，仍存在几个关键问题，并且高血压治疗、LVH消退和心血管事件减少之间的关键联系尚不清楚。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，可以有效地、经济地解决这些重要问题。SPRINT将是一项对照临床试验，旨在确定与标准对照（BP <140 mmHg）相比，将收缩压降至<120 mmHg是否会减少CV事件。拟议的SPRINT-HEART辅助研究对RFA HL10-024具有高度反应，并创新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个合适的临床地点，一种新的干预措施和一项大型随机临床事件试验。该研究将从SPRINT中招募340名参与者（每组170名），并在基线和18个月的随访中测量左室质量和舒张末期容积（EDV），以验证以下主要假设：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。该研究还将在随访期间（平均3.4年）确定SPRINT中左室质量和EDV与CV复合终点的关系，以检验以下次要假设：左室质量和重构的改善将与CV事件的减少相关。作为一项探索性目的，将测量强化降压组和标准对照组从基线到18个月随访期间左室应变、心肌纤维化、左房容积和主动脉僵硬度的变化。这将使该研究能够探索在SPRINT测试范围内的血压剧烈降低影响LVH和CV事件的潜在机制。通过确定这些更新颖的CMR措施对强化降压的反应，也将为它们在未来试验中的潜在应用奠定基础。最后，该研究将检查特别感兴趣的亚组中18个月CV结构和功能变化之间的关系，包括既往CV疾病的患者；那些75岁以上的人，以及那些患有慢性肾脏疾病的人。SPRINT- heart将检验无法解决的关键假设，挑战现有范式，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，并推进我们对左室肥厚（LVH）的理解及其管理公共卫生相关性：左室肥厚（LVH）在一般人群中很常见，是心血管（CV）事件的一个强大的独立预测因子，包括心脏病发作、心力衰竭和死亡。然而，预防或降低LVH所需的最佳血压控制（BP）水平尚不清楚，LVH应在多大程度上独立于BP进行靶向治疗尚不清楚。SPRINT-HEART是一种创新的、具有成本效益的方法，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)