Effect of Standard vs Intense Hypertension Management on Nighttime Blood Pressure

描述（由申请人提供）：高血压是心血管和肾脏疾病的主要风险因素，也是全球过早死亡的主要原因。早期的高血压研究表明，治疗高血压（BP）可降低患者患心血管疾病的风险和全因死亡率。在随后的研究中，当患者的治疗目标是中等收缩压目标（<150 mmHg）时，患者的心血管结局比目标更高时获得更大的改善。尽管观察数据表明，即使较低的血压目标也可能是有益的，但这在随机试验中尚未发现;相反，高血压的“强化”治疗（即，目标收缩压<120 mmHg）对参与者患肾脏疾病、心血管疾病或全因死亡率的风险没有影响。对于这种明显缺乏高血压目标益处的一个潜在解释是， 方案的目标是降低门诊血压，而不是门诊血压。动态血压监测（ABPM）允许在白天和晚上评估血压。在所有血压测量中，夜间收缩压似乎是心血管疾病和全因死亡率的最佳预测因子。由于最近评估高血压目标的试验不包括动态血压测量，因此强化治疗对夜间血压的影响在很大程度上是未知的。为了解决这一重要的知识差距，我们将在950名参与者中进行ABPM，作为正在进行的收缩压干预试验（SPRINT）的辅助研究的一部分。辅助研究的目的是评价强化与标准治疗的效果 基于临床的血压目标是夜间血压（主要结局），以及夜/日血压比、峰值血压时间、24小时血压和血压变异性（次要结局）。无论结果如何，完成拟议的辅助研究将显著影响未来高血压研究的方向。如果BP的强化治疗与较低的夜间BP相关，则母研究SPRINT的结果将证明实现较低的夜间BP对重要的心血管和肾脏结局的影响（积极或消极）。或者，总体SPRINT结果为阴性，加上辅助研究发现两组夜间血压“无差异”，这表明需要进行未来的试验，以确定降低夜间血压是否会降低CKD进展、终末期肾病和心血管疾病的风险。此外，拟定的研究将通过阐明强烈的临床BP目标对下降、峰值BP的时间和BP变异性的影响，提供对主要SPRINT结果的机制性见解。最后，这项辅助研究将为主要研究者提供大型、正在进行的临床试验中的领导经验，从而为候选人作为独立临床研究者的职业生涯做好准备，其长期目标是通过针对动态血压特定组分的治疗降低高血压相关的发病率和死亡率。

DESCRIPTION (provided by applicant): Hypertension is a major risk factor for cardiovascular and renal disease, and a leading cause of premature mortality worldwide. Early hypertension studies showed that treating elevated blood pressure (BP) reduces patients' risk of cardiovascular disease and all-cause mortality. In subsequent research, patients achieved greater improvement in cardiovascular outcomes when their treatment was aimed at a moderate systolic BP target (<150mmHg) than at higher targets. Although observational data suggest that even lower BP targets may be beneficial, this has not been seen in randomized trials; instead, "intense" treatment of hypertension (i.e., to a target systolic BP <120mmHg) was found to have no effect on participants' risk for renal disease, cardiovascular disease, or all-cause mortality. One potential explanation for this apparent lack of benefit of intense BP targets is that the study protocols targeted reductions in clinic BP rather than ambulatory BP. Ambulatory BP monitoring (ABPM) allows for assessment of BP throughout the day and night. Of all the BP measurements, nighttime systolic BP appears to be the best predictor of cardiovascular disease and all-cause mortality. Because recent trials assessing intense BP targets did not include ambulatory BP measurements, the effect of intensive treatment on nighttime BP is largely unknown. To address this important gap in knowledge, we will conduct ABPM in 950 participants as part of an ancillary study to the ongoing Systolic Blood Pressure Intervention Trial (SPRINT). The goal of the ancillary study is to evaluate the effect of intensive vs. standard clinic based BP targets on nighttime BP (primary outcome), as well as night/day BP ratio, timing of peak BP, 24hr BP, and BP variability (secondary outcomes). Regardless of the outcomes, completion of the proposed ancillary study will significantly impact the direction of future hypertension research. If intensive treatment of BP is associated with lower nighttime BP, then results from the parent SPRINT study will demonstrate the effect (positive or negative) of achieving lower nighttime BP on important cardiovascular and renal outcomes. Alternatively, negative overall SPRINT results coupled with an ancillary study finding of "no difference" in nighttime BP between the groups will indicate the need for future trials to determine whether lowering nighttime BP reduces the risk for CKD progression, end-stage renal disease, and cardiovascular disease. In addition, the proposed study will provide mechanistic insight into the primary SPRINT results by elucidating the effect of intense clinic BP targets on dipping, the timing of peak BP, and BP variability. Lastly, this ancillary study will provide the principal investigator with leadership experience within a large, ongoing clinical trial, thereby preparing the candidate for a career as an independent clinical researcher, with the long- term goal of reducing the morbidity and mortality associated with hypertension through therapies targeted to specific components of ambulatory BP.