Pulse wave velocity and central aortic pressure outcomes in SPRINT

SPRINT 中的脉搏波速度和中心主动脉压结果

• 批准号: 8528703
• 负责人: Mark A Supiano
• 金额: $ 34.93万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8528703
• 关键词: Address; Age; Age-associated memory impairment; Aging; Albumins; Aldosterone; Ancillary Study; Biological Markers; Biological Preservation; Blood Pressure; Blood Vessels; Calcium; Cardiovascular system; Chronic Kidney Failure; Clinic; Clinical; Clinical Trials Design; Dementia; Disease; Event; Goals; Hemoglobin; Hemoglobin concentration result; Hormones; Hypertension; Insulin; Intervention Trial; Living Costs; Measures; Methodology; Mortality Decline; Outcome; Parathyroid gland; Parents; Patients; Peripheral; Phosphorus; Physiologic pulse; Population; Population Study; Quality of life; Randomized; Randomized Clinical Trials; Recruitment Activity; Renal function; Renin; Renin-Angiotensin-Aldosterone System; Serum; Study Subject; Testing; Time; Uric Acid; arm; blood pressure regulation; cardiovascular disorder risk; cardiovascular risk factor; clinically relevant; cognitive function; cost effectiveness; falls; fasting glucose; follow-up; glucose metabolism; insulin sensitivity; interest; peripheral blood; pressure; primary outcome; secondary outcome; therapeutic target; treatment as usual; treatment program; urinary

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.

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，以确定强化治疗组（目标 SBP < 120 mm Hg）和常规护理组（目标 SBP < 140 mm Hg）之间产生的外周（肱动脉）收缩压 (SBP) 差异是否会伴随血管僵硬度测量值（主动脉脉搏波）的显着差异。 速度、aPWV）和中央（主动脉）血压。这项 SPRINT 辅助研究提出的总体假设是，血管僵硬度的测量将预测主要的 SPRINT 结果，与所达到的外周 SBP 无关。提出了三个主要具体目标。 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（和子目标 1，中心血压测量值）是否会低于常规护理治疗组。 具体目标 2：确定 SPRINT 研究受试者达到的 aPWV（和子目标 2，中心血压测量值）（根据基线值进行调整）是否将成为主要 SPRINT 结局（心血管疾病事件）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。 具体目标 3：确定 aPWV 和中心血压与血管老化和僵硬度相关生物标志物（空腹血糖、胰岛素、胰岛素敏感性、血红蛋白 A1C、肾素和醛固酮）以及与慢性肾脏病相关的标志物（CKD - 血清钙、磷、甲状旁腺激素水平、尿酸和尿白蛋白）之间的基线关联。 这项对 SPRINT 具有时间敏感性的辅助研究将通过评估临床相关的葡萄糖代谢生物标志物、胰岛素敏感性、肾素-血管紧张素-醛固酮系统以及与 CKD 相关的标志物，添加有关血管僵硬潜在机制的重要信息。此外，通过使用经过验证的、可重复的、非侵入性方法收集血管硬度 (aPWV) 和中央主动脉血压的基线（随机）和纵向、年度测量值，将确定这些测量值对于主要 SPRINT 临床结果的价值。 目前尚无大规模研究表明，血管硬度的降低本身（与外周血压下降无关）是否可以更好地预测临床获益。此外，尚无研究评估目标 SBP 为 120 mm Hg 的患者的 aPWV 或中央主动脉血压的变化。增加血管硬度测量将有助于确定这些结果是否应被视为超出外周血压的治疗目标。因此，在这项 SPRINT 辅助研究中添加 aPWV 和中央主动脉血压测量以及几种血管僵硬度生物标志物是对母试验的重要科学补充。