Nephrotic Syndrome, Cardiovascular Disease Risk and the Effect of Statin Therapy

描述（由申请人提供）：肾病综合征是多种疾病实体的常见表现，包括罕见的原发性肾小球疾病，如微小病变、局灶节段性肾小球硬化和膜性肾病。该综合征的特征是显著的蛋白尿、低血清白蛋白、水肿和高脂血症。心血管疾病是慢性肾脏病患者的主要并发症。由于与肾病综合征相关的蛋白尿和高脂血症，推测肾病综合征患者发生心血管疾病的风险增加，但尚未确定该肾病患者亚组的风险程度、特定风险因素的影响和治疗效果。我们建议对原发性肾小球疾病所致肾病综合征患者进行回顾性队列研究，以确定心血管疾病的风险，确定危险因素，并确定他汀类药物（HMG-CoA还原酶抑制剂）治疗的效果。目的1：确定肾病综合征患者与非肾病综合征患者相比发生心血管事件的风险。目的2：探讨肾病综合征患者心血管事件的危险因素。目标3：确定使用HMG-CoA还原酶抑制剂（他汀类药物）治疗是否与肾病综合征患者心血管事件风险降低相关，并确定这种相关性与非肾病综合征患者相比是否存在差异。我们将使用健康改善网络（THIN），一个英国。初级保健数据库由从全科医生收集的900多万名患者的匿名数据组成。它包含诊断代码，处方信息和实验室数据，特别适合于基于人群的罕见疾病研究。我们将使用考克斯比例风险模型进行生存分析，以确定心血管事件的风险比，然后确定风险因素并确定他汀类药物治疗对该风险的影响。拟议的项目将使用th申请人获得的技能，致力于临床流行病学硕士学位，特别是流行病学，生物统计分析和研究设计的基础知识。本申请人对该项目的长期目标是管理和分析数据，准备出版手稿，为未来的研究提供信息，并为未来的K赠款申请提供数据。

DESCRIPTION (provided by applicant): Nephrotic syndrome is a common presentation of multiple disease entities, including rare primary glomerular disease such as minimal change disease, focal segmental glomeruloscerosis and membranous nephropathy. The syndrome is characterized by significant proteinuria, low serum albumin, edema and hyperlipidemia. Cardiovascular disease is the major morbidity for patients with chronic kidney disease. Patients with nephrotic syndrome are presumed to have an increased risk of cardiovascular disease due to the proteinuria and hyperlipidemia associated with the syndrome, but the magnitude of risk, the impact of specific risk factors, and effect of therapy has not been established in this subset of kidney disease patients. We propose a retrospective cohort study of patients with nephrotic syndrome due to primary glomerular diseases to determine the risk of cardiovascular disease, to identify risk factors and to determine the effect of statin (HMG-CoA reducatse inhibitors) therapy. AIM 1: To determine the risk of cardiovascular events in nephrotic syndrome patients compared to patients without nephrotic syndrome. AIM 2: To identify risk factors for cardiovascular events within nephrotic syndrome patients. AIM 3: To determine if the use of HMG-CoA reductase inhibitor (statin) therapy is associated with decreased risk of cardiovascular events in nephrotic syndrome, and to determine if this association differs compared to patients without nephrotic syndrome. We will use the health improvement network (THIN), a U.K. primary care database composed of anonymous data collected from the general practitioners of more than 9 million patients. It contains diagnostic codes, prescription information and laboratory data and is uniquely suited for population-based studies of rare diseases. We will perform a survival analysis, using a Cox proportional hazards model, to determine the hazard ratio for cardiovascular events, and then to identify risk factors and to determine effect of statin therapy on that hazard. The proposed project will use the skills that th applicant gained working towards a Masters of Science in Clinical Epidemiology, specifically fundamentals of epidemiology, biostatistical analysis and study design. This applicant's long-term objectives for this project are to manage and analyze the data, prepare manuscripts for publication, inform future studies and build upon the data for a future application to a K grant application.