A New Paradigm for Hypertension in the Elderly- Beyond Age

描述（由申请人提供）：超过60%的65岁以上的成年人患有高血压（BP），但老年人高血压的最佳管理仍然存在争议。与中年人降低血压明显有益的证据相反，老年人的数据 血压不稳定和高血压可能不是所有老年人的危险因素。我们最近报道，在年龄65岁的国家健康和营养检查调查的参与者中，高血压是全因和心血管（CV）死亡的危险因素，仅在健康状况较好的人中（定义为20英尺步行测试的快速步行）。相比之下，高血压不是慢走者的风险因素。此外，降低血压在所有老年人中的益处仍然是一个争论的问题;最近对80岁及以上人群的荟萃分析报告称，血压治疗对死亡率没有益处，并且试验间存在显著异质性。最后，人们越来越担心与降低血压治疗相关的潜在危害。在一些研究中，过度降低血压，特别是舒张压，与死亡和心血管事件的风险增加有关。在拟议的研究中，我们提出了一种新的范式，在复杂的老龄化过程中，BP与老年人的不良后果的关联被认为是在设置。我们的长期目标是通过定义类似健康状况的亚群，可靠地识别BP治疗有益的老年人和治疗无效甚至有害的老年人。具体而言，目标1提出了从四个领域阐明因素（功能，认知/心理，自我评定的健康和生理），可以识别高收缩压与死亡和CV事件风险较高密切相关的老年人，以及与之无关的老年人，使用来自三个NIH资助的队列的数据：心血管健康研究（CHS），健康老龄化和身体组成（健康ABC）和萨克拉门托地区拉丁美洲老龄化研究（SALSA）。在目标2中，我们将评估舒张压在不同健康状况水平中的作用。最后，基于这些观察性队列的结果，在目标3中，我们将评估这些因素是否可以在两项随机对照试验中识别出降低血压治疗最大获益的老年人：老年人收缩性高血压（SHEP）和小型皮质下卒中的二级预防（SPS 3）。由于试验参与者比美国人口更健康，我们还将使用最先进的因果推理方法评估观察性研究中的治疗效果，该方法可以纠正标准分析方法的偏倚。这些目标的完成将大大提高我们对老年人高血压重要性的认识;将提高我们识别将从BP治疗中受益的老年人的能力;将允许系统地了解缺乏BP治疗证据的人群;并将指导未来老年人高血压试验的设计。

DESCRIPTION (provided by applicant): Over 60% of adults age � 65 years have high blood pressure (BP), but optimal management of high BP in the elderly remains controversial. Contrary to evidence in middle age that lowering BP is clearly beneficial, data in older adults are inconsistent and high BP may not be a risk factor in all elders. We recently reported that, among participants in the National Health and Nutrition Examination Survey age e65 years, high BP was a risk factor for all-cause and cardiovascular (CV) death only among persons in better health status (defined as fast walking of a 20-ft walk test). In contrast, high BP was not a risk factor among slow walkers. Additionally, the benefit of lowering BP in all elders remains an issue of debate; a recent meta-analysis in persons age 80 years and older reported no benefit of BP treatment on mortality, and significant heterogeneity across trials. Finally, there is growin concern for potential harms associated with treatment to lower BP. Excessive lowering of BP, particularly diastolic, has been associated with increased risk for death and cardiovascular events in some studies. In the proposed research, we propose a novel paradigm where the associations of BP with adverse outcomes in older persons are considered in the setting of the complex aging process. Our long-term goal is to reliably identify elderly persons in whom BP treatment is beneficial and those in whom treatment is ineffective or even harmful, by defining subpopulations of similar health status. Specifically, aim 1 proposes to elucidate factors from four domains (functional, cognitive/mental, self-rated health, and physiologic) that can identify elderly persons in whom high systolic BP is strongly associated with higher risk for death and CV events, and those in whom it is not, using data from three NIH-funded cohorts: Cardiovascular Health Study (CHS), Health Aging and Body Composition (Health ABC) and Sacramento Area Latino Study of Aging (SALSA). In aim 2, we will evaluate the role of diastolic BP across level of health status. Finally, based on findings from these observational cohorts, in aim 3 we will evaluate whether these factors can identify elderly persons in whom treatment to lower BP is of maximum benefit in two randomized controlled trials: the Systolic Hypertension in the Elderly (SHEP) and the Secondary Prevention of Small Subcortical Strokes (SPS3). Since participants in trials are healthier than the U.S. population, we will also evaluate the effect of treatment in the observational studies, using state-of-the-art causal inference methods, which can correct for the bias of standard analytic approaches. Completion of these aims will substantially advance our understanding of the importance of high BP in older adults; will improve our ability to identify elderly persons who will benefit from BP treatment; will allow a systematic understanding of groups in whom evidence for BP treatment is lacking; and will guide design of future trials of hypertension in elderly adults.