Intensive Blood Pressure Reduction to Lessen Functional Decline

强化降压以减轻功能衰退

• 批准号: 8529411
• 负责人: William Barry White
• 金额: $ 60.41万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8529411
• 关键词: Anisotropy; Antihypertensive Agents; Bladder Control; Blood Pressure; Brain; Brain region; Clinic; Clinical; Cognition; Cognitive; Data; Deterioration; Diffusion Magnetic Resonance Imaging; Etiology; Evaluation; Functional Imaging; Gait; Goals; Hour; Impairment; Knowledge; Laboratories; Lead; Lesion; Link; Location; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediating; Progress Reports; Randomized; Randomized Clinical Trials; Risk Factors; Severities; Speed; Structure; Time; Tissues; Urinary Incontinence; Walking; age group; blood pressure regulation; clinically relevant; cognitive function; executive function; functional decline; functional disability; indexing; longitudinal analysis; normotensive; older patient; processing speed; randomized trial; systolic hypertension; treatment effect; urinary; white matter

DESCRIPTION (provided by applicant): Data from our 4-year longitudinal study entitled "Brain changes and risk factors causing impaired mobility" have shown important relations among 24-hour systolic BP, progression of white matter hyperintensity (WMH) lesions and impaired mobility. Hence, in this application, we are proposing a randomized trial to reduce 24- hour ambulatory systolic BP (24ASBP) to 2 levels (usual vs. intensive ABP control) to mitigate the brain changes (WMHs) that are associated with impaired mobility. An increasing body of knowledge has related WMH to functional deterioration of mobility, urinary control and cognition. In baseline data from the precursor to this proposal we performed hypothesis-driven evaluations of WMH within brain regions (rWMH) known to be critical to mobility, cognition or voiding. These studies confirmed an association between rWMH and functional assessments suggesting that specific WM damage was linked to impaired function. While the 3 studies used different rWMHs (function dependent), a subsequent pooled analysis using rWMHs important for function demonstrated powerful correlations between rWMH and global WMH (tWMH) with r values of 0.5-0.9 for 8 of 10 structures). The tWMH predicted functional measures of mobility, executive function/processing speed and urinary function nearly as well as the best regional measures. The tWMH independently explains 5-11% of the variability for mobility, executive function/processing speed, and urinary incontinence severity and is a sensitive (r = 0.7-0.8) predictor of functional decline. Odds of decline in each of the 3 functional domains increased 1.5 to 2.4 fold with each 1% increase in tWMH. Ambulatory BP (ABP) data (but not clinic BP data) showed that in those subjects whose initial and 2 year 24-h systolic BP was <130 mmHg, significantly less WMH was observed than those whose 24-h systolic BP was >140 mmHg. Increases in ABP and WMH were significantly linked to less effective mobility documented by slower usual and maximal gait velocity and increased turn and stair descent time. Cognitive function was also diminished in the group with higher ABPs. Thus, small differences in 24-h systolic BP (10 mmHg), considered within the normotensive range for this age group, can result in clinically relevant differences in the accrual of tWMH and results in decreases in mobility and some aspects of cognitive function. The goal of the present proposal is to assess causality between 24-h systolic BP and reductions in mobility, cognitive and urinary function associated with WMH changes in brain as well as microstructural integrity as determined by diffusion tensor imaging in older people. The study will determine the impact of reducing the 24-h systolic BP to a goal of <125 mmHg (intensive BP control) vs. a goal of <140 mmHg (standard BP control). This separation of the ABP levels should achieve >10 mmHg differences between the groups that we believe is a key factor for reducing mobility impairment associated with WMH in older patients with systolic hypertension. This will be the first trial to study the ability to slow progression of WMHs to halt the resultant functional impairment by intensive reduction of ABP.

描述（申请人提供）：我们4年纵向研究的数据题为“大脑变化和危险因素，导致流动性受损”，显示了24小时收缩压BP之间的重要关系，白质高强度（WMH）病变的进展和迁移率受损。因此，在此应用中，我们提出了一项随机试验，以将24小时的卧床收缩期BP（24ASBP）降低至2个级别（通常与密集的ABP控制），以减轻与迁移率受损相关的大脑变化（WMHS）。越来越多的知识与迁移性，尿控制和认知的功能恶化有关。在从前体到该提案的基线数据中，我们对已知对迁移率，认知或空白至关重要的大脑区域（RWMH）进行了假设驱动的WMH评估。这些研究证实了RWMH与功能评估之间的关联，表明特定的WM损伤与功能受损有关。尽管这三项研究使用了不同的RWMH（函数依赖性），但随后使用RWMH的汇总分析对功能的重要性表现出RWMH和全局WMH（TWMH）之间的强大相关性，而R值为10个结构中的8个，R值为0.5-0.9）。 TWMH预测了行动能力，执行功能/处理速度和尿功能的功能度量，几乎和最佳区域度量一样。 TWMH独立地解释了移动性，执行功能/处理速度和尿失禁严重程度的5-11％，并且是功能下降的敏感（r = 0.7-0.8）的预测指标。 3个功能域中每个功能域下降的几率增加了1.5至2.4倍，TWMH的每1％增加。 卧床BP（ABP）数据（但没有临床BP数据）表明，在那些初始和2年24小时收缩压BP <130 mmHg的受试者中，观察到的WMH比24小时收缩压> 140 mmHg的受试者观察到了WMH。 ABP和WMH的增加与效率较低的移动性显着相关，该效率较慢，通常的步态速度较慢，最大步态速度以及增加的转弯和楼梯下降时间。在较高的ABP的组中，认知功能也降低了。因此，在该年龄段的正常范围内考虑的24小时收缩BP（10 mmHg）的微小差异可能会导致TWMH的临床相关差异，并导致迁移率降低和认知功能的某些方面。本提案的目的是评估与WMH大脑变化以及由老年人扩散张量成像确定的与WMH变化以及微结构完整性相关的24小时收缩BP和降低的因果关系。这项研究将确定将24小时收缩BP减少到<125 mmHg（密集的BP控制）的影响，而目标的目标<140 mmHg（标准BP控制）。 ABP水平的分离应在我们认为是减少与WMH相关的迁移率障碍的关键因素之间实现> 10 mmHg的差异。这将是研究降低WMH进展能够通过大量减少ABP停止功能障碍的第一个试验。