A New Paradigm for Hypertension in the Elderly- Beyond Age

描述（由申请人提供）：超过60%的≥65岁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。与中年人降压明显有益的证据相反，老年人的数据不一致，高血压可能不是所有老年人的危险因素。我们最近报道，在国家健康和营养调查的参与者中，年龄在65岁的人，只有在健康状况较好的人（定义为20英尺步行测试的快速步行）中，高血压是全因和心血管（CV）死亡的危险因素。相比之下，高血压并不是慢行者的危险因素。此外，降低血压对所有老年人的益处仍然是一个有争议的问题；最近一项针对80岁及以上人群的荟萃分析报告称，BP治疗对死亡率没有益处，且试验之间存在显著的异质性。最后，人们越来越关注降低血压治疗的潜在危害。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。在我们提出的研究中，我们提出了一个新的范式，在复杂的衰老过程中考虑老年人BP与不良后果的关联。我们的长期目标是通过确定健康状况相似的亚群，可靠地确定血压治疗对哪些老年人有益，哪些老年人治疗无效甚至有害。具体来说，目的1提出从四个领域（功能、认知/心理、自我评估健康和生理）阐明因素，这些因素可以识别高收缩压与死亡和心血管事件高风险密切相关的老年人，以及那些不是这样的老年人，使用美国国立卫生研究院资助的三个队列的数据：心血管健康研究（CHS）、健康老龄化和身体成分（health ABC）和萨克拉门托地区拉丁裔老龄化研究（SALSA）。在目标2中，我们将评估舒张压在健康状态水平上的作用。最后，基于这些观察性队列的研究结果，在目的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降压治疗最大获益的老年人：老年人收缩期高血压（SHEP）和小皮质下卒中二级预防（SPS3）。由于试验参与者比美国人群更健康，我们还将评估观察性研究中的治疗效果，使用最先进的因果推理方法，这可以纠正标准分析方法的偏差。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理解；将提高我们识别将受益于BP治疗的老年人的能力；可以系统地了解缺乏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.