Sudden Cardiac Death in Middle Age

描述(由申请人提供)：据估计，每年的发病率为300,000-350,000，占美国所有心血管死亡人数的50%，心脏性猝死(SCD)是一种对公共健康具有重大影响的疾病。尽管复苏科学的治疗不断进步，但院外心脏骤停患者的存活率为10%，这使得SCD的预测和预防至关重要。虽然SCD的风险与年龄的增加密切相关，但表现在中年(35-59岁；约.占所有SCD的30%)是造成社会负担的最大因素。然而，已发表的SCD研究几乎完全集中在老年患者(�60岁)上，部分原因是现有心血管队列研究中中年SCD病例数量不足。我们最近报道的证据表明，与老年相比，中年的SCD具有独特的特征，这表明识别中年特有的SCD机制的重要性。中年SCD患者更有可能在没有事先警告的情况下出现，肥胖症和非白人起更重要的作用。这一建议的总体假设是，对与中年SCD相关的新因素进行详细和集中的检查将增强对机制的理解，并有助于改进SCD风险预测和预防。我们的具体目标是1)确定在中年引发致命性心律失常的恶性冠状动脉事件的特征；2)确定导致SCD风险的新的肥胖相关危险因素；以及3)确定中年SCD风险最高的患者亚群。12年前，我们发起了俄勒冈州猝死研究(Oregon SUDS)，以确定SCD的新风险预测因素。这项对俄勒冈州波特兰市100万居民进行的大型研究继续积累了相当数量的SCD病例和对照。迫切需要确定中年SCD的风险预测因素，这是目前SCD最大的知识缺口。已建立的俄勒冈州SUDS为独特的发现人群提供了足够数量的受试者，并有机会利用现有的详细临床和生物标记物信息。识别SCD风险的临床和机械相关预测因子的可能性很高，这将加强SCD的预测和预防。

DESCRIPTION (provided by applicant): With an estimated annual incidence of 300,000-350,000 and accounting for 50% of all cardiovascular deaths in the US, sudden cardiac death (SCD) is a condition with significant implications for public health. Despite ongoing treatment advances in resuscitation science, survival among out-of-hospital cardiac arrest victims is <10%, making SCD prediction and prevention essential. While SCD risk is strongly associated with increasing age, manifestation in middle age (35-59 yr; approx. 30% of all SCD) is the most significant contributor to societal burden. However, published studies of SCD have focused almost exclusively on older patients (�60 yr), partly explained by insufficient numbers of middle-aged SCD cases among existing cardiovascular cohort studies. We have recently reported evidence for a distinctive profile of SCD in middle age compared to older age, indicating the significance of identifying middle age-specific SCD mechanisms. Middle aged SCD patients were more likely to present without prior warning, with obesity and non-white race playing a more important role. The overall hypothesis of this proposal is that a detailed and focused examination of novel factors associated with SCD in middle age will enhance the understanding of mechanisms and contribute to improved SCD risk prediction and prevention. Our specific aims are 1) To identify features of malignant coronary events that provoke lethal arrhythmias in middle age 2) To identify novel obesity-related risk factors contributing to SCD risk; and 3) To identify patient subgroups at highest risk of SCD in middle age. Over twelve years ago, we initiated the Oregon Sudden Unexpected Death Study (Oregon SUDS) to identify novel risk predictors for SCD. This large study among one million residents of the Portland, Oregon metro area continues to accrue a significant number of SCD cases and controls. The critical need to identify risk predictors for SCD in middle age currently represents the largest knowledge gap in SCD. The established Oregon SUDS provides a unique discovery population with sufficient numbers of subjects, coupled with the opportunity to leverage existing detailed clinical and biomarker information. There is a high likelihood of identifying clinically and mechanistically relevant predictors of SCD risk that will enhance prediction and prevention of SCD.