Pulse wave velocity and central aortic pressure outcomes in SPRINT

描述（申请人提供）：收缩压干预试验（SPRINT）提供了一个独特的机会，以确定外周血中的差异是否（肱动脉）收缩压（SBP）将在强化治疗组之间发展（目标SBP < 120 mm Hg）和常规护理组（目标SBP < 140 mm Hg）将伴随血管僵硬度（主动脉脉搏波速度，aPWV）和中心（主动脉）BP测量的显著差异。在这项SPRINT辅助研究中提出的总体假设是，血管硬度的测量将预测主要SPRINT结局，而与达到的外周SBP无关。提出了三个主要的具体目标。 具体目标1：确定随机分配至强化治疗组的SPRINT研究受试者在随机分配后第3年的aPWV（和子目标1，中心血压测量值）是否低于常规治疗组。 具体目标二：确定SPRINT研究受试者达到的aPWV（和子目标2，中心BP测量值）（根据基线值调整）是否是主要SPRINT结局（CV疾病事件）以及全因死亡率、肾功能下降、痴呆事件发生率和年龄相关认知下降的独立预测因子。 具体目标3：确定基线时aPWV与中心血压、血管老化和僵硬的相关生物标志物（空腹血糖、胰岛素、胰岛素敏感性、血红蛋白A1 C、肾素和醛固酮）以及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）之间的相关性。 这项对时间敏感的SPRINT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，增加有关血管僵硬潜在机制的重要信息。此外，通过使用经验证的、可重现的、无创方法收集基线（随机化时）和纵向、年度血管硬度（aPWV）和中心主动脉BP测量值，将确定这些测量值对主要SPRINT临床结局的价值。 没有大规模的研究已经解决了血管硬度本身的降低-独立于外周血压的下降-是否提供了更好的临床获益预测。此外，没有研究评估目标SBP 120 mm Hg治疗患者的aPWV或中心主动脉血压的变化。增加血管僵硬度的测量将有助于确定这些结果是否应被视为超过外周血压的治疗目标。因此，在这项SPRINT辅助研究中增加aPWV和中心主动脉血压测量以及血管僵硬度的几种生物标志物是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.