Longitudinal Impact of Antihypertensive Polypharmacy on Geriatric Syndromes

描述(申请人提供)：高血压(特别是孤立的收缩压)是老年人最常见的慢性疾病，也是心脑血管疾病的主要危险因素。以前的随机对照研究表明，对老年人(65岁以上)进行血压治疗可以有效并减少高血压相关的并发症。然而，这些有益的发现是否适用于85岁以上的脆弱社区老年人，以及 有时可能需要使用多种降压药(即多药联用)来控制血压。事实上，在老年人中使用多种抗高血压药物与增加行动能力问题和认知障碍的风险有关。这项拟议研究的长期目标是通过确定使用抗高血压药物的益处和风险的大小来增强老年人的健康，以便未来的处方指南可以更多地基于证据，减少对专家意见的依赖。采用纵向设计，近期目标是确定在社区居住的患有高血压的老年人中使用抗高血压药物的潜在益处和风险，并进行五年的随访。抗高血压药物将被定义为来自以下八类药物：1)β受体阻滞剂；2) 外周α受体阻滞剂；3)钙通道阻滞剂；4)血管紧张素转换酶抑制剂；5)血管紧张素受体阻滞剂；6)直接血管扩张剂；7)利尿剂和8)中枢阿尔法阻滞剂。在目标1中，我们将通过确定降压药的使用(如上述四种替代方法所定义的)和血压控制(定义为d140/90毫米汞柱)和高血压相关并发症(即因心脑血管疾病住院或死亡)之间的关联来检验潜在的益处。目标1在高血压患者中测试的特定假设是，与非暴露于高血压的老年人相比，服用降压药的参与者在进行多变量分析中的倾向得分匹配和重要协变量调整后，更有可能控制血压，并减少与高血压相关的并发症。在目标2中，我们将通过确定使用降压药(如上述四种替代方法所定义的)和移动性问题(短身体表现电池[SPPB]和步速)和认知功能下降(通过改进的简易智力状态检查[3MS]和CLOX 1测试来衡量)之间的关联来检查潜在的风险。目的2在高血压患者中需要检验的特定假设是，与非高血压暴露的老年人相比，在多变量分析中，在倾向得分匹配并调整重要协变量(例如，血压)后，使用降压药的参与者(由下面详细介绍的四种替代方法定义)在3MS、CLOX1、SPPB和通常的步行速度超过6米的表现将更差。 与公共卫生相关：目前的建议建立在我们之前成功的NIA资助的赠款(R01和R56)的基础上，这些赠款使用丰富的和先前存在的NIA资助的Health ABC研究数据库检查了中枢神经系统药物和特定的自我报告的老年综合征。这项提案的资金将使我们能够将我们的工作扩展到抗高血压药物，并检查重要的可测量的老年结果(即功能状态和认知)、生理指标(即血压控制)以及发病率和死亡率(即因心脑血管疾病住院和死亡)。这些研究与NIA的优先比较有效性研究领域是一致的。

DESCRIPTION (provided by applicant): Hypertension (especially isolated systolic) is the most common chronic condition in older adults and is a major risk factor for both cardiovascular and cerebrovascular diseases. Previous randomized controlled studies have shown that blood pressure treatment in older adults (65+) can be effective and reduce hypertension-related complications. However there is uncertainty regarding the generalizability of these beneficial findings to frail community dwelling older adults 85+ years of age and the potential risks that the sometimes necessary use of multiple anti-hypertensives (i.e., polypharmacy) to control blood pressure may have. Indeed, the use of multiple anti-hypertensives in older adults has been linked to increased risk of mobility problems and cognitive impairment. The long term objective of the proposed research is to enhance the health of the elderly by determining the magnitude of the benefits and risks of antihypertensive use so that future prescribing guidelines can be more evidence based and less dependent on expert opinion. Using a longitudinal design, the immediate objective is to determine the potential benefits and risks of antihypertensive use in community dwelling older adults with hypertension over a five year follow up. Anti-hypertensives will be operationally defined as medications from the following eight classes: 1) beta blockers; 2) peripheral alpha blockers; 3) calcium channel blockers; 4) angiotensin converting enzyme inhibitors; 5) angiotensin receptor blockers; 6) direct vasodilators; 7) diuretics and 8) central alpha blockers. In AIM 1, we will examine potential benefits by determining the association between antihypertensive use (as defined by four alternative approaches above) and blood pressure control (defined as d 140/90 mmHg) and hypertension-related complications (i.e., adjudicated hospitalization or death due to cardiovascular and cerebrovascular diseases). The Aim 1 specific hypotheses to be tested among those with hypertension are that, compared with non exposed elders, participants with antihypertensive use will be more likely to have blood pressure control and less likely to have hypertension-related complications after propensity score matching and adjusting for important covariates in multivariable analyses. In Aim 2, we will examine potential risks by determining the association between antihypertensive use (as defined by four alternative approaches above) and mobility problems (Short Physical Performance Battery [SPPB], and gait speed), and cognitive function decline (as measured by the Modified Mini-Mental State Examination [3MS] and the CLOX 1 Test). Aim 2 specific hypotheses to be tested among those with hypertension are that, compared with non exposed elders, participants with antihypertensive use (as defined by four alternative approaches detailed below) will have worse performance on the 3MS, CLOX1, the SPPB, and usual walking pace over six meters after propensity score matching and adjusting for important covariates (e.g., blood pressure) in multivariable analyses. PUBLIC HEALTH RELEVANCE: The current proposal builds on our previous and successful NIA funded grants (R01 and R56) that examined CNS medications and specific self-reported geriatric syndromes using the rich and pre-existing NIA funded Health ABC study database. Funding of this proposal will allow us to extend our work to anti-hypertensives and examine important measured geriatric outcomes (i.e., functional status and cognition), physiologic measures (i.e., blood pressure control), and morbidity and mortality (i.e., hospitalization and death due to cardiovascular and cerebrovascular disease). Such studies are consistent with NIA's priority comparative effectiveness research area.