Sudden Cardiac Death in Middle Age

描述（由申请方提供）：心源性猝死（SCD）是一种对公共卫生具有重大影响的疾病，估计年发病率为300，000 - 350，000，占美国所有心血管死亡的50%。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<10%，因此SCD的预测和预防至关重要。虽然SCD风险与年龄增长密切相关，但中年（35-59岁;约10岁）的表现占所有SCD的30%）是社会负担的最重要贡献者。然而，已发表的SCD研究几乎完全集中在老年患者（60岁），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，与老年人相比，中年人的SCD具有独特的特征，这表明识别中年特定SCD机制的重要性。中年SCD患者更可能在没有事先警告的情况下出现，肥胖和非白人种族起着更重要的作用。这项提议的总体假设是，对中年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，并有助于改善SCD风险预测和预防。我们的具体目标是：1）确定中年人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风险因素; 3）确定中年SCD风险最高的患者亚组。 十二年前，我们发起了俄勒冈州意外猝死研究（俄勒冈州SUDS），以确定SCD的新风险预测因子。这项在俄勒冈州波特兰大都会区的100万居民中进行的大型研究继续积累大量的SCD病例和对照。目前，确定中年SCD风险预测因子的迫切需要代表了SCD中最大的知识缺口。已建立的俄勒冈州SUDS提供了一个独特的发现人群，具有足够数量的受试者，以及利用现有详细临床和生物标志物信息的机会。很有可能识别出SCD风险的临床和机械相关预测因子，这将增强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.