Prevalence and predictors of asymptomatic atrial fibrillation in the community

说明(申请人提供)：房颤是缺血性中风的重要危险因素，在老年人中尤为常见。目前的知识建立在临床病例的基础上；心房颤动的短暂、通常无症状发作的频率，通常在持续性心房颤动发生之前，尚不清楚，也不知道与其相关的中风风险。此外，其他常见的房性和室性心律失常的频率，以及它们与中风风险的潜在关联，也只是部分已知。一项以社区为基础的前瞻性研究计划在1200名65岁以上的无卒中志愿者中进行，主要目的如下：1.评估未确诊的房颤在多民族老年人队列中的患病率，并描述其按性别和种族的分布；2.探讨心脏亚临床疾病、心血管危险因素和选定的生物标志物作为未确诊房颤的潜在预测因子的作用；3.评估室上性心动过速、频发房性早搏等可能与卒中有关的其他房性心律失常和室性心律失常(频发室性早搏)的患病率；4.在调整了常规血管危险因素后，确定多民族老年人队列中与未确诊的心房颤动和其他心律失常相关的中风、心肌梗死和血管死亡的风险。研究队列将从 之前资助的心血管异常和脑损伤(CABL)研究，基于正在进行的曼哈顿北部研究(NOMAS)和NOMAS本身。未诊断的房颤和其他心律失常将通过使用一种新的、经过验证的贴片心脏记录器连续记录14天的心律来进行评估。除了左心室质量和几何形状外，还将评估新的左心室收缩功能(左心室应变)和左心室舒张期功能(通过组织多普勒)的超声心动图指标。左房形态和功能将在3D回声图像(左房容积和排空分数)上进行评估，并使用心电重构指标(P波持续时间和离散度)进行评估。生物标志物将被测量为心房颤动的预测因子，探索不同的致病途径：心房扩张和 亚临床心功能不全(N-T proBNP)、炎症(高敏C反应蛋白、IL-6)、亚临床心肌损伤/缺血(肌钙蛋白I)、血栓形成(D-二聚体)、心房纤维化(转化生长因子β1)。受试者将接受每年一次的电话访谈，以确定中风、心肌梗死(如果反应积极，则亲自进行评估)和死亡。假定的预测因素和未诊断的房颤的优势比将通过Logistic回归来计算。房颤/其他心律失常和心血管事件的危险比将根据COX比例风险模型计算，并调整血管危险因素。本提案将填补我们在老年人房颤/其他心律失常的全球负担及其与中风和其他血管事件的关系方面的知识空白，并将确定发生这些心律失常的风险较高的受试者，可以针对这些受试者进行预防性干预。

DESCRIPTION (provided by applicant): Atrial fibrillation is a strong risk factor for ischemic stroke, and is especially frequent in the elderly. The current knowledge is based on clinically established cases; the frequency of short, often asymptomatic episodes of atrial fibrillation, which often precede the onset of sustained atrial fibrillation, is not known, and neither is their associated stroke risk. Also, the frequency of other common atrial and ventricular arrhythmias, and their potential association with stroke risk, is only partially known. A prospective community-based study is proposed on 1200 stroke-free volunteers over the age of 65 years with the following primary aims: 1. To evaluate the prevalence of undiagnosed atrial fibrillation in a multiethnic elderly cohort and describe its distribution by sex and race-ethnicity; 2. To investigate the role of cardiac subclinical disease, cardiovascular risk factors and selected biomarkers as potential predictors of undiagnosed atrial fibrillation; 3. To evaluate the prevalence of other atrial arrhythmias (supraventricular tachycardia, frequent atrial premature contractions) and ventricular arrhythmias (frequent ventricular premature contractions) possibly related to stroke; 4. To determine the risk of stroke, myocardial infarction and vascular death associated with undiagnosed atrial fibrillation and other arrhythmias in a multiethnic elderly cohort after adjusting for conventional vascular risk factors. The study cohort will be drawn from the previously funded Cardiovascular Abnormalities and Brain Lesions (CABL) study, based on the ongoing Northern Manhattan Study (NOMAS), and from NOMAS itself. Undiagnosed atrial fibrillation and other arrhythmias will be evaluated by means of 14-day continuous recording of cardiac rhythm using a novel, validated patch-based cardiac recorder. Novel echocardiographic indicators of left ventricular systolic (LV strain) and diastolic function (by tissue Doppler) willbe evaluated, in addition to LV mass and geometry. Left atrial morphology and function will be assessed on 3D echo images (LA volumes and emptying fraction) and using ECG indicators of electrical remodeling (P wave duration and dispersion). Biomarkers will be measured as predictors of atrial fibrillation that explore different pathogenic pathways: atrial distention and subclinical cardiac dysfunction (N-T pro BNP), inflammation (high-sensitivity CRP, IL-6), subclinical myocardial damage/ischemia (troponin I), thrombosis (D-dimer), atrial fibrosis (TGF beta1). Subjects will be followed by annual telephone interviews to ascertain stroke, myocardial infarction (with in- person evaluation in case of positive responses) and death. Odds ratio for putative predictors and undiagnosed atrial fibrillation will be calculated by logistic regression. Hazard ratios for atrial fibrillation/other arrhythmias and CV events will be calculated by Cox proportional hazards model, adjusting for vascular risk factors. The present proposal will fill gaps in our knowledge on the global burden of atrial fibrillation/other arrhythmias in the elderly and their relationship with stroke and other vascular events, and will identify subjects at higher risk of developing these arrhythmias to whom preventative interventions could be addressed.