Pulse wave velocity and central aortic pressure outcomes in SPRINT

描述（由申请人提供）：收缩压干预试验（SPRINT）提供了一个独特的机会来确定强化治疗组（目标收缩压< 120毫米汞柱）和常规护理组（目标收缩压< 140毫米汞柱）之间的外周（肱）收缩压（SBP）差异是否会伴随血管硬度（主动脉脉冲波速度，aPWV）和中央（主动脉）血压的显著差异。在这项SPRINT辅助研究中提出的总体假设是，血管刚度的测量将预测SPRINT的主要结果，而不依赖于达到的周围收缩压。提出了三个主要的具体目标。具体目标1：确定在随机化后第三年随机分配到强化治疗组的SPRINT研究受试者的aPWV（和亚目标1，中央血压测量）是否低于常规护理治疗组。具体目标2：确定SPRINT研究受试者的aPWV（和亚目标2，中央血压测量）是否达到（根据基线值调整）将成为SPRINT主要结果（CV疾病事件）以及全因死亡率、肾功能下降、痴呆发生率和年龄相关认知能力下降的独立预测因子。特异性目的3：确定aPWV和中枢血压与血管老化和僵硬相关生物标志物（空腹血糖、胰岛素、胰岛素敏感性、血红蛋白A1C、肾素和醛固酮）和慢性肾脏疾病相关标志物（CKD -血清钙、磷、甲状旁腺激素水平、尿酸和尿白蛋白）之间的基线相关性。这项对SPRINT具有时间敏感性的辅助研究将通过评估葡萄糖代谢、胰岛素敏感性、肾素-血管紧张素-醛固酮系统和CKD相关标志物的临床相关生物标志物，为血管僵硬的潜在机制提供重要信息。此外，通过收集基线（随机化）和纵向、年度测量血管刚度（aPWV）和中央主动脉压，使用经过验证的、可重复的、无创的方法，这些测量对于SPRINT主要临床结果的价值将被确定。目前还没有大规模的研究表明血管僵硬度本身的降低（独立于外周血压的下降）是否能更好地预测临床疗效。此外，还没有研究评估在收缩压达到120毫米汞柱的患者中aPWV或中央主动脉压的变化。增加血管僵硬度的测量将有助于确定这些结果是否应该被视为高于周围血压的治疗目标。因此，在SPRINT辅助研究中增加aPWV和中央主动脉压测量以及几种血管硬度生物标志物是对母试验的重要科学补充。

DESCRIPTION (provided by applicant): The Systolic Blood Pressure Intervention Trial (SPRINT) affords a unique opportunity to determine if the difference in peripheral (brachial) systolic blood pressure (SBP) that will develop between the intensive treatment group (target SBP < 120 mm Hg) and the usual care group (target SBP < 140 mm Hg) will be accompanied by significant differences in measures of vascular stiffness (aortic pulse wave velocity, aPWV) and central (aortic) BP. The overall hypothesis addressed in this SPRINT ancillary study is that measures of vascular stiffness will be predictive of the main SPRINT outcomes independent of the achieved peripheral SBP. Three primary specific aims are proposed. Specific Aim 1: To determine if aPWV (and sub-aim 1, measures of central BP) in SPRINT study subjects randomized to the intensive treatment group at year three post-randomization will be lower compared to the usual care treatment group. Specific Aim 2: To determine if the aPWV (and sub-aim 2, measures of central BP) achieved (adjusted for baseline value) in SPRINT study subjects will be an independent predictor of the primary SPRINT outcomes (CV disease events) as well as all cause mortality, decline in renal function, rate of incident dementia and age-related cognitive decline. Specific Aim 3: To determine the associations at baseline between aPWV and central BP and relevant biomarkers of vascular aging and stiffness (fasting glucose, insulin, insulin sensitivity, hemoglobin A1C, and renin and aldosterone) and markers associated with chronic kidney disease (CKD - serum calcium, phosphorous, parathyroid hormone levels, uric acid and urinary albumin). This time-sensitive ancillary study to SPRINT will add important information regarding the underlying mechanisms for vascular stiffness by assessing clinically relevant biomarkers for glucose metabolism, insulin sensitivity, the renin-angiotensin-aldosterone system, and markers associated with CKD. In addition, by collecting baseline (at randomization) and longitudinal, annual measures of vascular stiffness (aPWV) and central aortic BP using a validated, reproducible, non-invasive methodology, the value of these measures with regard to the primary SPRINT clinical outcomes will be determined. No large scale studies have addressed whether reductions in vascular stiffness per se - independent of the fall in peripheral BP - provides a better predictor of clinical benefits. Moreover, no study has assessed the change in aPWV or central aortic BP in patients treated to a target SBP of 120 mm Hg. The addition of measures of vascular stiffness will help to determine if these outcomes should be considered as a therapeutic target over and above the peripheral BP achieved. The addition of aPWV and central aortic BP measures as well as several biomarkers of vascular stiffness in this SPRINT ancillary study are therefore important scientific additions to the parent trial.