Obesity in Pulmonary Arterial Hypertension

肥胖导致肺动脉高压

• 批准号: 10163252
• 负责人: Nadine Al-Naamani
• 金额: $ 19.4万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-10 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10163252
• 关键词: Adipose tissue; Advisory Committees; Affect; Age; Award; Biological Markers; Blood; Blood Vessels; Body fat; Body mass index; Body measure procedure; Chest; Clinical; Clinical Research; Cyclic GMP; Data; Deposition; Development; Diagnosis; Disease; Disease Outcome; Dual-Energy X-Ray Absorptiometry; Echocardiography; Educational Activities; Endocrine; Enrollment; Epidemiology; Ethnic Origin; Exercise; Experimental Models; Faculty; Fatty acid glycerol esters; Image; Insurance Coverage; Life Expectancy; Link; Lung; Measurement; Measures; Mediating; Mediation; Mediator of activation protein; Medical; Medicine; Mentors; Metabolic; Metabolic Pathway; Methodology; NOS3 gene; Nitric Oxide Pathway; Non obese; Obesity; Outcome; PGRN gene; Patients; Pennsylvania; Phenotype; Physicians; Physiological; Plasma; Process; Production; Program Development; Prospective Studies; Prospective cohort; Public Health; Pulmonary Circulation; Pulmonary Hypertension; Pulmonary Vascular Resistance; Pulmonary artery structure; Quality of life; Questionnaires; Race; Registries; Research Personnel; Retrospective Studies; Retrospective cohort; Right Ventricular Dysfunction; Right Ventricular Function; Risk; Risk Factors; Role; Scientist; Severity of illness; Socioeconomic Status; Subcutaneous Tissue; Surveys; Syndrome; Techniques; Time; Training; Training Programs; Universities; Vascular Diseases; Vasodilation; Venous; Ventricular; Visceral; Weight; Woman; Work; adipokines; arterial stiffness; autocrine; base; cardiovascular risk factor; career; career development; chest computed tomography; cohort; comorbidity; disorder subtype; hands on research; health related quality of life; hemodynamics; high body mass index; human model; improved; improved outcome; inhibitor/antagonist; interest; new therapeutic target; novel; obese patients; older patient; paracrine; patient subsets; phosphodiesterase V; pressure; professor; prospective; public health research; pulmonary arterial hypertension; sex; skills; subcutaneous; survival prediction

PROJECT SUMMARY This proposal describes a five-year training program for the development of a career in clinical research with a scientific focus on understanding the role of obesity in pulmonary arterial hypertension (PAH). This proposal will serve as a vehicle to developing into an independent investigator. To that end, we have established a training plan that includes mentoring, course-work, didactic educational activities, and hands-on research. Steven Kawut, MD, MS, (the primary mentor) is a tenured Professor of Medicine and Epidemiology. He has a track record of successfully mentoring fellows and junior faculty and holds a K24 to support his mentoring activities. An advisory committee has been assembled to guide the candidate's career development. The application focuses on three specific aims. First, in a large prospective cohort of incident patients with PAH, we will examine the impact of obesity measured by body mass index on survival and quality of life outcomes as measured by a general health related quality of life (QOL) questionnaire, the 12-item Medical Outcomes Short Form survey, and a disease-specific QOL questionnaire, the emPHasis-10. The planned analysis will allow for adjustment for potential confounders including disease severity, age, sex, race, ethnicity, socioeconomic status, and insurance coverage. Second, in a retrospective cohort of patients with PAH from the University of Pennsylvania, we will measure thoracic visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) using chest computed tomography and will examine the association of between VAT:SAT ratio and pulmonary hemodynamics and outcomes in this cohort, adjusting for potential confounders including age, sex, race/ethnicity and disease subtype. We will use causal mediation analysis to examine whether progranulin, an adipokine, is a mediator of these associations. Third, we will enroll patients with PAH in a prospective cohort and will obtain serial measurements of body fat using dual-energy X-ray absorptiometry along with serial echocardiograms over the course of one year. We will determine the associations between changes in body fat mass and RV strain over time adjusting for potential confounders including age, sex, disease subtype, disease severity and PAH therapy. Together, these three aims illuminate different phenotypes of obesity and their association with outcomes in PAH. By combining these novel techniques, the applicant hopes to begin to define the different phenotypes of obesity and understand the underlying pathobiologic processes in the hopes of identifying potential novel therapeutic targets to improve survival and quality of life of patients with PAH.

项目概要 该提案描述了一个为期五年的临床研究职业发展培训计划 科学重点是了解肥胖在肺动脉高压 (PAH) 中的作用。这 提案将作为发展成为独立调查员的工具。为此，我们有 制定了培训计划，包括指导、课程作业、教学活动和实践 研究。 Steven Kawut，医学博士、理学硕士（主要导师）是医学和流行病学终身教授。 他拥有成功指导研究员和初级教师的记录，并拥有 K24 来支持他的工作 辅导活动。已经成立了一个咨询委员会来指导候选人的职业发展。 该应用程序侧重于三个具体目标。首先，在一个大型前瞻性事件患者队列中 PAH，我们将研究通过体重指数衡量的肥胖对生存和生活质量的影响 结果通过一般健康相关生活质量 (QOL) 调查问卷、12 项医疗 结果简表调查和特定疾病的 QOL 调查问卷 emPHasis-10。计划的 分析将允许调整潜在的混杂因素，包括疾病严重程度、年龄、性别、种族、民族、 社会经济地位和保险范围。 其次，在宾夕法尼亚大学的 PAH 患者回顾性队列中，我们将 使用胸部计算机测量胸部内脏脂肪组织 (VAT) 和皮下脂肪组织 (SAT) 断层扫描并将检查 VAT:SAT 比率与肺血流动力学之间的关联 该队列的结果，调整潜在的混杂因素，包括年龄、性别、种族/民族和疾病 亚型。我们将使用因果中介分析来检查颗粒体蛋白前体（一种脂肪因子）是否是以下因素的中介者： 这些协会。 第三，我们将 PAH 患者纳入前瞻性队列，并获得一系列身体测量结果 在一年的时间里，使用双能 X 射线吸收测定法和连续超声心动图来测量脂肪。我们 将确定身体脂肪量变化与 RV 应变随时间的变化之间的关联，调整 潜在的混杂因素包括年龄、性别、疾病亚型、疾病严重程度和 PAH 治疗。 这三个目标共同阐明了肥胖的不同表型及其与结果的关联 在多环芳烃中。通过结合这些新技术，申请人希望开始定义不同的表型 肥胖的研究并了解其潜在的病理生物学过程，希望能够发现潜在的新发现 治疗目标是提高 PAH 患者的生存率和生活质量。