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SBP&lt；120 mm Hg)和常规护理组(目标SBP&lt；140 mm Hg)之间的外周(臂)收缩压(SBP)是否会伴随着血管僵硬(主动脉脉搏波速度，aPWV)和中央(主动脉)血压的显著差异。在这项短跑辅助研究中提出的总体假设是，血管僵硬的测量将独立于实现的外周SBP来预测主要的短跑结果。提出了三个主要的具体目标。具体目标1：确定Sprint研究受试者在随机化后第三年被随机分配到强化治疗组的aPWV(和次级目标1，中枢血压测量)是否会低于常规护理治疗组。具体目标2：确定在Sprint研究对象中实现的aPWV(和子目标2，中枢血压测量)(根据基准值调整)是否将成为主要Sprint结果(心血管疾病事件)以及所有原因死亡率、肾功能下降、痴呆症发生率和与年龄相关的认知下降的独立预测因子。具体目标3：确定基线时aPWV和中枢血压与血管老化和僵硬的相关生物标记物(空腹血糖、胰岛素、胰岛素敏感性、血红蛋白A1C、肾素和醛固酮)以及与慢性肾脏疾病相关的标记物(CKD-血清钙、磷、甲状旁腺激素水平、尿酸和尿白蛋白)的相关性。Sprint的这项时间敏感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-醛固酮系统以及与CKD相关的标记，增加有关血管僵硬潜在机制的重要信息。此外，通过使用一种经过验证的、可重复的、非侵入性的方法收集基线(随机)和纵向的年度血管硬度(APWV)和中央动脉血压测量，将确定这些测量在主要Sprint临床结果方面的价值。目前还没有大规模的研究表明，血管硬度的降低本身--与外周血压的下降无关--是否能更好地预测临床益处。此外，还没有研究评估目标SBP为120毫米汞柱的患者的aPWV或中央主动脉血压的变化。增加血管僵硬的测量将有助于确定这些结果是否应该被视为超出外周血压的治疗目标。因此，在这项Sprint辅助研究中，增加了aPWV和中央主动脉血压测量以及血管僵硬的几个生物标志物，是对母公司试验的重要科学补充。公共卫生相关性：项目描述与年龄相关的血压增加，再加上世界范围内老龄化人口的增加，意味着高血压是一个巨大的新兴全球公共卫生问题。随着年龄增长而形成的血管僵硬是高血压发病的主要因素。收缩压干预试验(Sprint)研究的这项辅助研究将调查可能有用的临床措施和血管僵硬的替代生物标记物，以确定是否应该将血管僵硬的测量作为治疗目标，而不是像Sprint研究的强化治疗组那样，将其作为降低外周收缩压的治疗目标。(摘要结束)

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. PUBLIC HEALTH RELEVANCE: Project Narrative The age-associated increase in blood pressure combined with the world-wide demographic increase in the aging population means that hypertension represents an enormous emerging global public health concern. Vascular stiffness that develops with aging is a major contributor to the development of hypertension. This ancillary study to the Systolic Blood Pressure Intervention Trial (SPRINT) study will investigate potentially useful clinical measures and surrogate biomarkers of vascular stiffness to determine if measures of vascular stiffness should be should be considered as a therapeutic target over and above the reduced peripheral systolic blood pressure that will be achieved in the intensive treatment arm of the SPRINT study. (End of Abstract)