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

基本信息

批准号：
8304263
负责人：
Elaine Hylek
金额：
$ 49.16万
依托单位：
BOSTON MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-30 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8304263
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

项目摘要

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）：中风是美国第三大死亡原因，也是导致残疾的主要原因。由心房颤动 (AF) 引起的心源性中风尤其具有破坏性，30 天死亡率为 25%。预计到 2020 年，房颤患者人数将达到 800 万，这将给老年人带来不成比例的负担。房颤的挑战和矛盾在于，许多中风的危险因素也是出血的危险因素，限制了高危人群抗凝治疗的使用。参加临床试验的患者通常与临床实践中的高风险患者几乎没有相似之处，因此很难推断治疗效果和安全性的估计。试验参与者更年轻，男性居多，医学复杂程度较低，症状较少，并且是专门为降低出血风险而选择的。尽管少数族裔的风险因素负担更大，但他们在 AF 试验人群中所占比例不到 5%。阿司匹林是治疗房颤的一种勉强有效的疗法，其引起出血的频率几乎与抗凝剂一样高，尤其是在老年人中。例如，由于老年人抗凝剂和抗血小板治疗的广泛使用，近年来颅内出血的发生率增加了五倍； 46%是致命的。迫切需要采取不伴随出血风险的预防策略来减轻房颤中卒中的影响。尽管高血糖、感染、加速高血压、心力衰竭和血脂异常等促炎刺激是凝血酶生成的有效触发因素，但它们对房颤卒中结果的影响尚未研究。 HMG CoA 还原酶抑制剂（他汀类药物）的抗炎和抗血栓特性为减轻 AF 中风严重程度（大小）的假设提供了生物学原理。实验研究报告血小板沉积减少；血小板介导的凝血酶生成，并减少梗塞体积。他汀类药物、可改变和不可改变的卒中危险因素、抗血栓治疗和房颤卒中结果之间的关系尚未阐明。为了解决这些知识差距，我们将收集 2006 年至 2010 年期间连续 AF 中风入院（缺血性中风和颅内出血）的大型队列（n = 2,500，35% 少数族裔代表性不足，43% > 75 岁），来自 3 个战略地点实现以下目标： 1. 按年龄、性别、种族/民族确定 AF 卒中致残率和 30 天病死率； 2. 研究急性血栓前炎症触发因素与房颤卒中严重程度的关系； 3. 研究抗血栓治疗（包括他汀类药物）与 AF 卒中严重程度的危险因素之间的关系。我们的应用程序将通过合作研究人员和机构的独特和互补优势来实现这些目标：波士顿医学中心、阿拉巴马大学和宾夕法尼亚州盖辛格卫生系统。我们的应用程序将揭示 AF 卒中的关键知识差距，制定减轻卒中严重程度的目标策略，并评估不同 AF 患者群体中各种卒中风险范围内抗血栓和他汀类药物治疗与卒中结果的关系。公共卫生相关性：减少中风致残和中风死亡的种族/民族差异是美国紧迫的健康问题。通过这项提案，我们的目标是为关键的代表性不足的人口亚群确定中风预防方法。我们的提案将揭示房颤卒中的关键知识差距、减轻卒中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治疗在不同房颤患者群体中对卒中风险的影响。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Who, when, and how to reverse non-vitamin K oral anticoagulants.

谁、何时以及如何逆转非维生素 K 口服抗凝剂。

DOI：
发表时间：
2016-02
期刊：
影响因子：
4
作者：
Aronis, Konstantinos N;Hylek, Elaine M
通讯作者：
Hylek, Elaine M

Effect of warfarin on intracranial hemorrhage incidence and fatal outcomes.

华法林对颅内出血发生率和致命结果的影响。

DOI：
发表时间：
2013
期刊：
影响因子：
7.5
作者：
Witt, Daniel M;Delate, Thomas;Hylek, Elaine M;Clark, Nathan P;Crowther, Mark A;Dentali, Francesco;Ageno, Walter;Martinez, Kerri D;Garcia, David A
通讯作者：
Garcia, David A

National assessment of warfarin anticoagulation therapy for stroke prevention in atrial fibrillation.

华法林抗凝治疗预防房颤卒中的国家评估。

DOI：
发表时间：
2014-04-01
期刊：
影响因子：
37.8
作者：
Dlott, Jeffrey S;George, Roberta A;Huang, Xiaohua;Odeh, Mouneer;Kaufman, Harvey W;Ansell, Jack;Hylek, Elaine M
通讯作者：
Hylek, Elaine M

Explaining racial disparities in anticoagulation control: results from a study of patients at the Veterans Administration.

解释抗凝控制方面的种族差异：退伍军人管理局对患者进行的一项研究结果。

DOI：
发表时间：
2015-05
期刊：
影响因子：
0
作者：
Rao, Sowmya R;Reisman, Joel I;Kressin, Nancy R;Berlowitz, Dan R;Ash, Arlene S;Ozonoff, Al;Miller, Donald R;Hylek, Elaine M;Zhao, Shibei;Rose, Adam J
通讯作者：
Rose, Adam J

Anticoagulation therapy for atrial fibrillation.

房颤的抗凝治疗。