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

项目总结 肥胖是一个严重的公共健康问题，也是各种疾病日益流行的原因。 降低生活质量和增加死亡风险的并存。肥胖是一个重要的危险因素。 慢性肾脏疾病(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，释放 炎性细胞因子增加了肥胖患者患CKD和CVD的风险。因此， 肥胖与高血压的发展高度相关。随着肥胖症的增加，患者容易 导致肾小球高滤过、肾脏钠重吸收放大、细胞外容量超负荷和受损 排钠。因此，脂肪组织过剩的患者通常比瘦的患者在生理上更复杂。 高血压患者的风险更高，出现与高血压相关的许多不良后果的风险也更大。 尽管如此，人们对合适的血压目标或特定降压的效果知之甚少。 影响肥胖患者血压控制程度的药物。 建议研究的目的是为了更好地了解1)肥胖是否会影响 降压级别对血压控制程度的影响；2)血压控制程度对血压的影响。 肥胖、高血压患者慢性肾脏病和心血管疾病的发生发展。我们将使用预期的24- 一小时动态血压监测及回溯性电子纵向分析 来自两个超大型卫生系统的卫生记录数据，考虑到时间更新的暴露情况 和混血儿。我们还将使用电子健康记录数据来评估初始 肥胖者开始降压治疗的降压类别选择或血压阈值与 非肥胖症患者。使用多学科的方法，我们预计这一设计将促进未来 优化肥胖高血压患者的医疗管理。 我目前是由NIH F32基金资助的，拥有内科和肾病专业的董事会认证， 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物管理的研究 在生活在美国的数百万肥胖和高血压患者中。我以前的经验和培训 在纵向分析中，我已经为从事研究中提出的工作做好了准备，并对此表示赞赏 我建议强化教育以病人为中心的高血压研究，超前纵向分析 技术、药物流行病学方法和心血管流行病学结果研究。与 得到我经验丰富的指导团队的支持，以及牛津大学提供的充足资源 宾夕法尼亚州临床流行病学和生物统计学中心，我的目标是培养一个持久的职业生涯 作为一名独立的内科科学家进行研究，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.