Epidemiologic Study of Sick Sinus Syndrome

描述(申请人提供)：病态窦房结综合征(SSS)是一种以窦房结的症状性功能障碍为特征的疾病。在美国和其他西方国家，SSS占心脏起搏器植入适应症的30%-50%。尽管它的负担和相关的费用，以前没有研究探索的发病率和危险因素的SSS在一般人群。如果确定了可改变的危险因素，则存在在许多个体中可以预防SSS的可能性。同样，关于SSS对心血管疾病和死亡率总体风险的影响的信息也很有限。我们建议使用来自美国社区动脉粥样硬化风险(ARIC)研究和心血管健康研究(CHS)的现有数据，这两个基于社区的前瞻性队列包括21,680名男性和女性，白人和非裔美国人，基线年龄为45岁及以上，以解决以下目标：(1)计算ARIC和CHS中SSS的年龄、性别和种族特定的发病率，并估计每年在美国发生的SSS事件的总数；(2)确定与SSS发病率相关的生活方式、临床变量和生物标记物，并开发工具，帮助预测无症状个体中SSS的未来风险；(3)评价SSS发生率与随后发生其他心血管事件(冠心病、心力衰竭、房颤)和总死亡率的关系。作为一个探索性目标，我们将使用候选基因和全基因组方法来探索SSS的遗传决定因素。将研究的风险因素包括但不限于社会经济变量、吸烟、体力活动、饮食、吸烟、体重指数和其他肥胖指标、血压、糖尿病、血胆固醇、心电参数以及心血管疾病(冠心病、心力衰竭和中风)或慢性肾脏疾病的病史。感兴趣的生物标志物包括：C-反应蛋白、NT-proBNP和肌钙蛋白T。SSS事件将从住院出院代码和联邦医疗保险(来自联邦医疗保险和医疗补助服务中心(CMS))数据中确定。总体而言，我们的研究将包括近20年来来自不同种族/民族和地理背景的2万多人的样本。我们预计将确定400多起SSS事件。这项拟议的研究是了解老年人一种相对常见的心脏疾病的流行病学和病因的有效途径，并将为制定SSS的预防策略和培养我们的心脏电生理学知识提供相关数据。 公共卫生相关性：病态窦房结综合征(SSS)占美国心脏起搏器植入的30%-50%。然而，关于它在人群中的分布，它的危险因素，以及它对心血管结局和死亡率的影响，人们知之甚少。拟议的研究将使用来自两个大型队列研究的可用数据来回答有关SSS流行病学的相关问题。这项研究的结果将提供对SSS和心脏电生理学的更好的了解，这最终可能导致对这种和其他心脏疾病，如房颤和心脏传导障碍的新的预防和治疗方法。

DESCRIPTION (provided by applicant): Sick sinus syndrome (SSS) is a disorder characterized by symptomatic dysfunction of the sinoatrial node. SSS accounts for 30-50% of indications for pacemaker implantations in the US and other Western countries. Despite its burden and associated costs, no previous studies have explored the incidence and risk factors for SSS in the general population. If modifiable risk factors are identified, the possibility exists that SSS might be preventable in many individuals. Similarly, limited information exists on the impact of SSS on the overall risk of cardiovascular disease and mortality. We propose to use available data from the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS), two community-based prospective cohorts in the US including 21,680 men and women, whites and African-Americans, aged 45 and older at baseline, to address the following aims: (1) To calculate the age, gender and race-specific incidence of SSS in ARIC and CHS, and estimate the total annual number of SSS events occurring in the US; (2) To identify lifestyles, clinical variables and biomarkers associated with the incidence of SSS, and to develop tools that help to predict the future risk of SSS in asymptomatic individuals; (3) To evaluate the association of SSS incidence with the subsequent risk of other cardiovascular outcomes (coronary heart disease, heart failure, atrial fibrillation) and total mortality. As an exploratory aim, we will explore genetic determinants of SSS using candidate gene and genome-wide approaches. Risk factors that will be studied include, but are not limited to, socioeconomic variables, smoking, physical activity, diet, smoking, body mass index and other adiposity measures, blood pressure, diabetes, blood cholesterol, electrocardiographic parameters, and history of cardiovascular disease (coronary heart disease, heart failure, and stroke) or chronic kidney disease. Biomarkers of interest include: C-reactive protein, NT-proBNP, and troponin T. SSS incident events will be identified from hospitalization discharge codes and Medicare (from the Center for Medicare and Medicaid Services (CMS)) data. Overall, our study will include a sample of more than 20,000 individuals from a diverse racial/ethnic and geographical background followed for almost 20 years. We expect to identify more than 400 incident cases of SSS. The proposed research constitutes an efficient approach to understand the epidemiology and etiopathogenesis of a relatively common cardiac condition in the elderly, and will provide relevant data to develop preventive strategies for SSS and foster our knowledge of cardiac electrophysiology. PUBLIC HEALTH RELEVANCE: Sick sinus syndrome (SSS) accounts for 30-50% of pacemaker implantations in the US. Still, little is known about its distribution in the population, its risk factors, and its impact on cardiovascular outcomes and mortality. The proposed research will use available data from two large cohort studies to answer relevant questions about the epidemiology of SSS. Results from this study will provide a better understanding of SSS and cardiac electrophysiology, which could lead eventually to new preventive and therapeutic approaches for this and other cardiac conditions such as atrial fibrillation and cardiac conduction disturbances.