Effect of Statins and Modifiable Factors on Stroke Outcome in Atrial Fibrillation

他汀类药物和可改变因素对心房颤动卒中结果的影响

• 批准号: 8040481
• 负责人: Elaine Hylek
• 金额: $ 54.71万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8040481
• 关键词: 3 year old; Academic Medical Centers; Acute; Address; Admission activity; Age; Alabama; American; American Heart Association; Anti-Inflammatory Agents; Anti-inflammatory; Anticoagulant therapy; Anticoagulants; Aspirin; Atrial Fibrillation; Biological; Blood Platelets; Blood Pressure; Body mass index; Boston; Case Fatality Rates; Cessation of life; Characteristics; Clinical Trials; Coagulation Process; Complex; Deposition; Dyslipidemias; Elderly; Enrollment; Environment; Ethnic Origin; Generations; Glucose; Health; Health system; Heart Atrium; Heart failure; Hemorrhage; Hispanics; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperglycemia; Hypertension; Individual; Infarction; Infection; Inflammation; Inflammatory; Information Systems; Institution; Intracranial Hemorrhages; Ischemic Stroke; Knowledge; Left Ventricular Function; Link; Lipids; Mediating; Minority; Morbidity - disease rate; Outcome; Participant; Patients; Pennsylvania; Population; Prevention approach; Prevention strategy; Property; Race; Relative (related person); Renal function; Reporting; Research Personnel; Risk; Risk Factors; Role; Rupture; Safety; Severities; Site; Stimulus; Stroke; Stroke prevention; Subgroup; Thrombin; Thromboplastin; Thrombosis; Thrombus; Time; Treatment Efficacy; Underrepresented Minority; United States National Institutes of Health; Ursidae Family; Vascular Diseases; Venous; Ventricular; Woman; clinical practice; cohort; disability; effective therapy; electronic data; high risk; male; mortality; patient population; public health relevance; racial and ethnic disparities; research study; sex

DESCRIPTION (provided by applicant): Stroke is the third leading cause of mortality and a leading cause of disability in the U.S. Cardioembolic strokes resulting from atrial fibrillation (AF) are particularly devastating, with a 30-day mortality of 25%. The number of individuals with AF is projected to reach 8 million by 2020, and will disproportionately burden the elderly. The challenge and paradox of AF is that many of the risk factors for stroke are also risk factors for hemorrhage, limiting the use of anticoagulant therapy among those at greatest risk. Patients enrolled in clinical trials often bear little resemblance to the higher risk patients in clinical practice making it difficult to extrapolate estimates of treatment efficacy and safety. Trial participants are younger, more often male, less medically complex, less symptomatic, and specifically selected for lower bleeding risk. Despite their greater burden of risk factors, minorities have constituted less than 5% of AF trial populations. Aspirin is a marginally effective therapy in AF and causes bleeding almost as frequently as anticoagulants, particularly in the elderly. For instance, the rate of intracranial hemorrhage has quintupled in recent years, due to expanded use of anticoagulants and antiplatelet therapy in older adults; 46% are fatal. Preventive strategies without attendant bleeding risk are urgently needed to mitigate the impact of stroke in AF. Although proinflammatory stimuli like hyperglycemia, infection, accelerated hypertension, heart failure, and dyslipidemia are potent triggers for thrombin generation, their effect on AF stroke outcomes has not been studied. The anti-inflammatory and antithrombotic properties of HMG CoA-reductase inhibitors (statins) provide a biological rationale to hypothesize reduced severity (size) of AF stroke. Experimental studies report reduced platelet deposition; platelet mediated thrombin generation, and reduced infarct volume. The relations among statins, modifiable and nonmodifiable stroke risk factors, antithrombotic therapy and AF stroke outcomes have yet to be elucidated. To address these knowledge gaps, we will assemble a large cohort of consecutive AF stroke admissions (ischemic stroke and intracranial hemorrhage) from 2006-2010 (n=2,500, 35% underrepresented minority, 43% >75 years of age) from 3 strategic sites to address the following aims: 1. To determine AF stroke disability and 30-day case fatality by age, sex, race/ethnicity; 2. To examine the relation of acute prothrombotic inflammatory triggers on stroke severity in AF; 3. To study the associations of antithrombotic treatment, including statins, and risk factors to stroke severity in AF. Our application will address these aims through the unique and complementary strengths of the collaborating investigators and institutions: Boston Medical Center, University of Alabama, and Geisinger Health System of Pennsylvania. Our application will inform critical knowledge gaps in AF stroke, target strategies to mitigate stroke severity, and assess the relations of antithrombotic and statin therapy to stroke outcomes across the spectrum of stroke risk among diverse AF patient populations. PUBLIC HEALTH RELEVANCE: Reduction of stroke disability and racial/ethnic disparities in stroke deaths is a pressing U.S. health concern. Through this proposal, we aim to identify stroke prevention approaches for key underrepresented demographic subgroups. Our proposal will inform critical knowledge gaps in AF stroke, target strategies to mitigate stroke severity, and assess the effects of antiplatelet, anticoagulant, and statin therapy among diverse AF patient populations across the spectrum of stroke risk.

描述（由申请人提供）：中风是死亡率的第三主要原因，也是由心房颤动（AF）引起的美国心脏符号中风的主要原因，特别是毁灭性的，死亡率为30天25％。预计到2020年，患有AF的人的人数将达到800万，并且老年人负担不成比例。 AF的挑战和悖论在于，中风的许多危险因素也是出血的危险因素，限制了风险最大的抗凝治疗的使用。参加临床试验的患者在临床实践中通常与较高的风险患者几乎没有相似之处，因此很难推断治疗功效和安全性的估计。试验参与者年轻，男性更常见，医学上不那么复杂，症状较低，专门为降低出血风险而被选中。尽管危险因素负担更大，但少数群体占AF试验人群的不到5％。阿司匹林是AF中有效的一种有效的治疗，导致出血几乎与抗凝剂一样频繁，尤其是在老年人中。例如，近年来，由于抗凝剂的使用和老年人抗血小板治疗的扩大，颅内出血的发生率已有Quintuplplepl。 46％是致命的。迫切需要采取预防性策略，而无需出血风险，以减轻中风对AF的影响。尽管促炎性刺激如高血糖，感染，加速性高血压，心力衰竭和血脂异常是凝血酶产生的有效触发因素，但尚未研究其对AF中风结果的影响。 HMG COA-还原酶抑制剂（他汀类药物）的抗炎和抗血栓性特性提供了一种生物学原理，以假设AF中风的严重程度降低（大小）。实验研究报告血小板沉积降低。血小板介导的凝血酶产生，并减少梗塞体积。他汀类药物，可修改和不可修改的中风风险因素，抗血栓疗法和AF中风结果之间的关系尚未阐明。 To address these knowledge gaps, we will assemble a large cohort of consecutive AF stroke admissions (ischemic stroke and intracranial hemorrhage) from 2006-2010 (n=2,500, 35% underrepresented minority, 43% >75 years of age) from 3 strategic sites to address the following aims: 1. To determine AF stroke disability and 30-day case fatality by age, sex, race/ethnicity; 2。检查AF中急性促血栓性炎症性触发器的关系； 3。研究抗血栓治疗的关联，包括他汀类药物和AF中卒中严重程度的危险因素。我们的申请将通过合作调查人员和机构的独特和互补优势来解决这些目标：波士顿医学中心，阿拉巴马大学和宾夕法尼亚州的盖辛格卫生系统。我们的应用程序将为AF中风中的关键知识差距提供依据，以减轻中风严重性的目标策略，并评估抗血栓和他汀类药物治疗与各种AF患者人群中中风风险范围的中风结果的关系。 公共卫生相关性：中风残疾和中风死亡中的种族/种族差异的减少是美国卫生问题。通过该提案，我们旨在确定预防中风的方法，用于主要代表性不足的人群亚组。我们的建议将为AF中风方面的关键知识差距，针对减轻中风严重程度的目标策略，并评估抗血小板，抗凝剂和他汀类药物疗法在各种中风风险范围内的影响。