Management of hypertension in obesity: Antihypertensive class effects, blood pressure control, and renal and cardiac outcomes

项目概要 肥胖是一个重要的公共卫生问题，是导致多种疾病日益流行的原因 降低生活质量并增加死亡风险的合并症。肥胖是重要的危险因素 慢性肾脏病（CKD）和心血管疾病（CVD）。肾素-血管紧张素-的上调 醛固酮系统、交感神经系统活动增强、血管僵硬和释放 炎症细胞因子会增加肥胖患者患 CKD 和 CVD 的风险。据此， 肥胖与高血压的发生密切相关。随着肥胖的增加，患者容易 肾小球过度滤过、肾钠重吸收放大、细胞外容量超负荷和受损 尿钠排泄。因此，脂肪组织过多的患者通常比瘦的患者生理更复杂。 高血压患者，并且发生与高血压相关的许多不良后果的风险更大。 尽管如此，人们对适当的血压目标或特定抗高血压药物的效果知之甚少。 肥胖患者血压控制程度的药物。 拟议研究的目的是更好地了解 1) 肥胖是否会影响 抗高血压类别对血压控制程度的影响，2) 血压控制程度对血压控制程度的影响 肥胖、高血压患者 CKD 和 CVD 的发生和进展。我们将使用预期的 24- 除了回顾性电子血压的纵向分析之外，还进行每小时动态血压监测 来自两个超大规模卫生系统的健康记录数据，考虑到时间更新的暴露情况 和混杂因素。我们还将使用电子健康记录数据来评估初始数据是否存在差异 肥胖者与肥胖者开始抗高血压治疗的抗高血压类别选择或血压阈值 非肥胖患者。使用多学科方法，我们预计这种设计将促进未来 优化肥胖和高血压患者的医疗管理。 我目前由 NIH F32 拨款资助，拥有内科和肾脏病学委员会认证， 以及宾夕法尼亚大学临床流行病学理学硕士学位。 K23 职业生涯 发展奖将使我能够开展旨在优化药理管理的研究 生活在美国的数百万肥胖、高血压患者。我之前的经历和培训 纵向分析让我做好了参与研究中提出的工作的准备，并将称赞 我提出的以患者为导向的高血压研究强化教育，高级纵向分析 技术、药物流行病学方法和心血管流行病学结果研究。随着 我经验丰富的导师团队的支持以及大学丰富的资源 宾夕法尼亚州临床流行病学和生物统计学中心，我的目标是培养持久的职业生涯 作为一名独立的医师科学家进行研究，并成为肾性高血压领域的领导者。

PROJECT SUMMARY Obesity is a critical public health issue, and is responsible for a growing prevalence of diverse comorbidities that reduce quality of life and increase mortality risk. Obesity is an important risk factor for chronic kidney disease (CKD) and cardiovascular disease (CVD). Upregulation of the renin-angiotensin- aldosterone system, heightened sympathetic nervous system activity, vascular stiffness, and release of inflammatory cytokines contribute to the increased risk of CKD and CVD in obese patients. Accordingly, obesity is highly associated with the development of hypertension. As adiposity increases, patients are prone to glomerular hyperfiltration, amplified renal sodium reabsorption, extracellular volume overload, and impaired natriuresis. Thus, patients with excess adipose tissue are often more physiologically complex than lean hypertensive patients, and are at greater risk for many adverse outcomes related to hypertension. Nonetheless, little is known about appropriate blood pressure goals or the effects of specific antihypertensive agents on degree of blood pressure control in obese patients. The objective of the proposed studies is to better understand 1) if adiposity influences the effect of antihypertensive class on degree of BP control, and 2) the effect that degree of BP control has on the development and progression of CKD and CVD in obese, hypertensive patients. We will use prospective 24- hour ambulatory blood pressure monitoring in addition to longitudinal analyses of retrospective electronic health record data from two extremely largescale health systems, taking into account time-updated exposures and confounders. We will also use the electronic health record data to assess if there is a difference in initial antihypertensive class selection or BP threshold for initiation of antihypertensive treatment in obese versus non-obese patients. Using a multidisciplinary approach, we anticipate that this design will facilitate future optimization of medical management of patients with obesity and hypertension. I am currently funded by an NIH F32 grant, with board certification in Internal Medicine and Nephrology, and a Masters of Science in Clinical Epidemiology from the University of Pennsylvania. The K23 Career Development Award will enable me to develop research aimed at optimizing the pharmacologic management of the millions of obese, hypertensive patients living in the United States. My previous experience and training in longitudinal analyses have prepared me to engage in the work proposed in the studies, and will compliment my proposed intensive education in patient-oriented hypertension research, advanced longitudinal analytic techniques, pharmacoepidemiologic methods, and cardiovascular epidemiologic outcomes research. With the support of my highly experienced mentorship team and the ample resources available at the University of Pennsylvania’s Center for Clinical Epidemiology and Biostatistics, my goal is to foster a career of enduring research as an independent physician scientist, and to become a leader in the field of renal hypertension.