Guiding next steps for SPRINT-MIND implementation: Identifying high-benefit subgroups and comparative effects of ARB- vs. ACEI-based regimens

指导 SPRINT-MIND 实施的后续步骤：确定高效益亚组以及 ARB 与基于 ACEI 的治疗方案的比较效果

• 批准号: 10052751
• 负责人: Adam P Bress
• 金额: $ 69.87万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10052751
• 关键词: Address; Affect; Aging; Alzheimer' s disease related dementia; Ancillary Study; Angiotensin II Receptor; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Benefits and Risks; Blood Pressure; Brain; Brain imaging; Calcium Channel Blockers; Cardiovascular system; Characteristics; Cognition; Cognitive; Data; Data Sources; Dementia; Dependence; Diabetes Mellitus; Diuretics; Dose; Elderly; Event; Health Benefit; Healthcare Systems; Human; Hypertension; Impaired cognition; Incidence; Intervention Trial; Kidney; Knowledge; Lead; Lesion; Machine Learning; Measures; Memory; Methods; Modernization; Outcome; Patients; Pharmaceutical Preparations; Population; Prevention; Prevention approach; Preventive; Public Health; Randomized; Randomized Clinical Trials; Regimen; Relative Risks; Renin-Angiotensin-Aldosterone System; Research; Risk; Risk Reduction; Safety; Sample Size; Serious Adverse Event; Structure; Subgroup; Testing; active comparator; adjudicate; base; blood pressure intervention; blood pressure regulation; brain volume; clinical practice; clinically significant; cognitive benefits; comparative; cost; cost efficient; dementia risk; design; disability; experience; follow-up; machine learning method; middle age; mild cognitive impairment; older patient; predictive modeling; randomized trial; response; secondary analysis; tool; white matter

PROJECT SUMMARY Alzheimer’s disease and related dementias (ADRD) are the leading cause of dependence and disability in the elderly population worldwide, costing the US healthcare system over $200 billion annually. Because ADRD represents a continuous irreversible physical and cognitive decline, identifying effective approaches for its prevention is imperative. Hypertension, particularly in midlife, is associated with an increased risk of cognitive decline and ADRD. Recent data from the randomized Systolic Blood Pressure (SBP) Intervention Trial (SPRINT) Memory and cognition IN Decreased hypertension (SPRINT MIND) demonstrated that intensive SBP control (<120 mmHg) reduced the combined incidence of adjudicated mild cognitive impairment (MCI) and probable dementia, as well as abnormal white matter lesion (WML) volume compared to standard BP control (<140 mmHg) over five years follow up. To maximize public health impact, it is critical to identify which patients derive the greatest cognitive and net (overall) benefit from intensive SBP treatment and if cognitive benefits were due to direct effects of specific antihypertensive medications on cognition independent of, or in addition to, their BP-lowering effect. Prior animal and human studies, as well as our preliminary data, suggest that angiotensin II receptor blockers (ARB) have greater effects on cognition than angiotensin-converting- enzyme inhibitors (ACEI). If verified, this finding would be significant since ARBs and ACEIs are currently among the medications most commonly prescribed to older adults and are thought to be equivalent in benefit and safety. Our objective is to answer remaining questions of how to safely implement SPRINT in older patients most likely to derive cognitive benefits from intensive SBP treatment. With its large sample size, 5 years follow-up, and high-quality repeated measures of rigorously adjudicated cognitive outcomes, brain imaging, and antihypertensive medication use, SPRINT MIND provides a unique, cost-efficient, and ideal setting to answer these questions. We aim to: (1) develop and validate a prediction tool that quantifies patients’ expected cognitive benefits and net (overall) benefit incorporating cognitive and cardiovascular benefit and risk of SAEs under intensive SBP treatment, and (2) determine comparative effects, including dose-response, of ARB- vs. ACEI-based antihypertensive medication regimens on cognitive and brain structure outcomes independent of SBP-lowering effects. Though SPRINT MIND is among the first randomized trials to demonstrate a beneficial preventive effect on cognition, it is uncertain how SPRINT-MIND should be implemented and in which patients. Successful completion of this project will guide next steps for implementation by determining: (1) which patients derive the greatest cognitive and net (overall) benefit from intensive SBP treatment and (2) if ARBs have greater beneficial effects on cognitive outcomes and WML volume than ACEIs, independent of their similar SBP lowering effects.

项目摘要 阿尔茨海默氏病和相关痴呆症（ADRD）是依赖和残疾的主要原因 全球老年人口，每年耗资超过2000亿美元的美国医疗保健系统。因为Adrd 代表着不可逆转的身体和认知能力下降，确定了其有效的方法 预防是必须的。高血压，特别是在中年的高血压，与认知的风险增加有关 衰落和adrd。来自随机收缩压（SBP）干预试验的最新数据 （冲刺）高血压降低（Sprint Mind）的记忆和认知证明了这一点 SBP对照（<120 mmHg）减少了调整后的轻度认知障碍（MCI）的综合事件 与标准BP相比 在五年内进行控制（<140 mmHg）。为了最大化公共卫生的影响，至关重要的是要确定哪个 患者得出最大的认知和净（总体）受益于密集的SBP治疗以及认知能力 益处是由于特定降压药对独立于或独立于认知的直接影响 此外，它们的降低BP效果。先前的动物和人类研究以及我们的初步数据表明 血管紧张素II接收器阻滞剂（ARB）对认知的影响比血管紧张素转换 - 酶抑制剂（ACEI）。如果得到验证，这一发现将很重要，因为ARB和ACEI当前是 在最常见的老年人处方的药物中，被认为是同等的。 和安全。我们的目的是回答有关如何安全地实施较旧的冲刺的剩余问题 患者最有可能通过强化SBP治疗获得认知益处。其样本量较大，5 多年的随访以及严格调整认知结果的高质量重复测量 Sprint Mind提供了成像和降压药的使用，提供了独特，经济高效且理想的 设置回答这些问题。我们的目标是：（1）开发和验证量化的预测工具 患者的预期认知益处和净（整体）益处，包括认知和 在密集的SBP治疗下，心血管益处和SAE的风险，（2）确定比较 效果，包括基于ARB的剂量反应，基于ACEI的降压药方案 认知和大脑结构结果与降低SBP的影响无关。虽然Sprint的头脑是 在第一个证明对认知有益预防作用的随机试验中，尚不确定如何 应该实施冲刺的心形。成功完成该项目将 指导下一步实施通过确定：（1）哪个患者获得了最大的认知和 净（总体）受益于密集型SBP治疗，（2）如果ARB对认知有更大的好处 结果和WML体积比ACEI，与它们相似的SBP降低效应无关。