Heart Failure Evaluation in Post-Menopausal Women: The Women's Health Initiative

描述（由申请人提供）：慢性心力衰竭（CHF）是美国唯一一种患病率和发病率正在增加的心血管疾病。尽管治疗取得了进展，但CHF患者的5年死亡率仍保持在50%左右，2005年因CHF住院的人数超过100万。老年女性占一般人群CHF患者的50%，但由于老年女性占CHF临床试验入组患者的不到20%，因此该人群的流行病学和治疗数据有限。基于来自小型回顾性研究的有限数据以及对内皮功能、神经激素激活和心肌重塑的有益作用，激素替代疗法（HRT）在降低女性CHF发病率方面具有潜在作用。然而，雌激素-孕酮HRT与心肌梗死（MI）风险增加相关，MI是CHF的重要危险因素。此外，没有数据检查HRT在绝经后女性CHF一级预防中的作用，或其对CHF患者生存率的影响。鉴于妇女健康倡议（WHI）的主要结果显示，HRT会增加MI、卒中和静脉血栓栓塞事件的风险，因此很难在前瞻性随机试验中验证我们的假设。我们的目的是评估27,347例绝经后妇女在WHI中HRT与CHF发生风险和随后死亡率之间的关系。中心假设是HRT将降低CHF发生率并改善CHF患者的生存率。我们的具体目标包括：1）研究基线时无CHF的参与者中HRT与CHF发病率之间的相关性; 2）研究发生CHF的参与者中HRT与全因死亡率之间的相关性; 3）基于CHF病因（缺血性与非缺血性）和收缩功能（受损与保留），研究HRT与CHF发病率和死亡率之间的相关性。这项研究是创新的，因为它使用了一种新的方法来识别CHF病例，使用现有最大的数据库来研究绝经后妇女HRT和CHF之间的关系。这些结果将进一步了解HRT在CHF预防和/或治疗中的作用，并有助于更好地了解老年女性CHF流行病学，老年女性占CHF风险人群的很大一部分。我们的研究具有成本效益，使用以前收集的数据，但从未为此特定目的进行分析。在可预见的未来，其他队列研究不太可能提供类似的数据。慢性心力衰竭是美国唯一一种患病率、发病率和死亡率不断上升的心血管疾病。尽管女性占心力衰竭患者的50%，但迄今为止很少有流行病学和临床研究涉及心力衰竭的性别特异性风险因素和治疗。基于有限的回顾性数据，激素替代治疗在降低女性心力衰竭发病率和相关死亡率方面具有潜在作用。考虑到妇女健康倡议的主要结果，即激素替代治疗增加了心肌梗死、中风和静脉血栓栓塞事件的风险，在前瞻性随机试验中验证我们的假设将是困难的。本申请的目的是评估激素替代治疗与27，347名参加妇女健康倡议的绝经后妇女发生心力衰竭和随后死亡率风险之间的关系。我们将使用现有最大的数据库来研究绝经后妇女激素替代治疗与心力衰竭之间的关系。这些结果将进一步了解激素替代疗法在心力衰竭预防和/或治疗中的作用，并将有助于更好地了解老年女性的心力衰竭流行病学，老年女性占心力衰竭风险人群的很大一部分。

DESCRIPTION (provided by applicant): Chronic heart failure (CHF) is the only cardiovascular disease in the United States for which the prevalence and morbidity are increasing. Despite treatment advances, 5-year mortality for patients with CHF remains around 50%, with over one million hospital admissions for CHF in 2005. Older women represent 50% of those with CHF in the general population, but limited epidemiologic and treatment data exist in this population because older women account for less than 20% of those enrolled in CHF clinical trials. Hormone replacement therapy (HRT) has a potential role in reducing CHF incidence in women, based on limited data from small, retrospective studies and beneficial effects on endothelial function, neurohormonal activation and myocardial remodeling. However, estrogen-progestin HRT is associated with increased risk of myocardial infarction (MI), an important risk factor for CHF. In addition, there are no data examining HRT in primary prevention of CHF among post-menopausal women, or its effects on survival in women who develop CHF. Given the main results of the Women's Health Initiative (WHI), which showed increased risk for MI, stroke and venous thromboembolic events with HRT, testing our hypothesis in a prospective randomized trial would be difficult. Our objective is to evaluate the association between HRT and risk of incident CHF and subsequent mortality in 27,347post-menopausal women in WHI. The central hypothesis is that HRT will reduce CHF incidence and improve survival among those who develop CHF. Our specific aims include: 1) To investigate the association between HRT and CHF incidence among participants free of CHF at baseline; 2) To examine the association between HRT and all-cause mortality among participants who develop CHF; 3) To explore the association between HRT and CHF incidence and mortality, based on CHF etiology (ischemic versus non- ischemic) and systolic function (impaired versus preserved). The proposed research is innovative because it uses a new approach to identifying CHF cases, using the largest existing database to study the relationship between HRT and CHF in post-menopausal women. The results will further the knowledge on the role of HRT in CHF prevention and/or treatment, and will contribute to the better understanding of CHF epidemiology in older women, who represent a large proportion of the population at risk for CHF. Our study is cost-effective, using data previously collected but never analyzed for this specific purpose. It is unlikely that other cohort studies will be able to provide similar data in the foreseeable future. Chronic heart failure is the only cardiovascular disease in the United States for which the prevalence, morbidity, and mortality are increasing. Despite the fact that women represent up to 50% of the heart failure patients, few epidemiological and clinical studies to date have addressed the gender specific risk factors and treatments for heart failure. Based on limited retrospective data, hormone replacement therapy has a potential role in reducing heart failure incidence and associated mortality in women. Given the main results of the Women's Health Initiative, which showed increased risk for myocardial infarction, stroke and venous thromboembolic events with hormone replacement therapy, testing our hypothesis in a prospective randomized trial would be difficult. The objective of this application is to evaluate the association between hormone replacement therapy and risk of incident heart failure and subsequent mortality in 27,347 post-menopausal women enrolled in Women's Health Initiative. We will be using the largest existing database to study the relationship between hormone replacement therapy and heart failure in post-menopausal women. The results will further the knowledge on the role of hormone replacement therapy in heart failure prevention and/or treatment, and will contribute to the better understanding of heart failure epidemiology in older women, who represent a large proportion of the population at risk for heart failure.