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)是美国唯一一种发病率和发病率都在上升的心血管疾病。尽管治疗取得了进步，慢性心力衰竭患者的5年死亡率仍保持在50%左右，2005年有100多万人因慢性心力衰竭住院。老年妇女占普通人群中CHF患者的50%，但这一人群的流行病学和治疗数据有限，因为老年妇女在参加CHF临床试验的患者中所占比例不到20%。激素替代疗法(HRT)在降低女性CHF发病率方面具有潜在作用，这是基于有限的小型回顾性研究数据，以及对内皮功能、神经激素激活和心肌重构的有益影响。然而，雌激素-孕激素替代疗法与心肌梗死(MI)风险增加有关，MI是CHF的一个重要危险因素。此外，还没有研究激素替代疗法在绝经后妇女CHF一级预防中的作用，或者它对发生CHF的妇女生存的影响的数据。鉴于妇女健康倡议(WHI)的主要结果显示，HRT增加了心肌梗塞、中风和静脉血栓栓子事件的风险，在前瞻性随机试验中验证我们的假设将是困难的。我们的目标是评估WHI中27,347名绝经后妇女的激素替代疗法与发生CHF的风险和随后的死亡率之间的关系。中心假设是，HRT将减少CHF的发生率，并提高CHF患者的存活率。我们的具体目标包括：1)调查基线状态下无CHF的参与者中HRT与CHF发病率的关系；2)研究HRT与发生CHF的参与者的全因死亡率之间的关系；3)基于CHF病因(缺血与非缺血)和收缩功能(受损与保留)，探讨HRT与CHF发病率和死亡率之间的关系。这项拟议的研究具有创新性，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女性HRT和CHF之间的关系。这一结果将进一步加深对HRT在CHF预防和/或治疗中作用的了解，并将有助于更好地了解老年妇女的CHF流行病学，她们占CHF风险人群的很大比例。我们的研究是具有成本效益的，使用了以前收集的数据，但从未为这一特定目的进行分析。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、发病率和死亡率都在上升的心血管疾病。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定风险因素和治疗方法。根据有限的回顾数据，激素替代疗法在降低女性心力衰竭发生率和相关死亡率方面具有潜在作用。鉴于女性健康倡议的主要结果显示，使用激素替代疗法会增加心肌梗死、中风和静脉血栓栓塞症的风险，在前瞻性随机试验中验证我们的假设将是困难的。这项申请的目的是评估激素替代疗法与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的风险之间的关系。我们将使用现有最大的数据库来研究激素替代疗法与绝经后妇女心力衰竭的关系。这一结果将进一步加深对激素替代疗法在心力衰竭预防和/或治疗中作用的了解，并将有助于更好地了解老年妇女的心力衰竭流行病学，她们占心力衰竭风险人群的很大比例。

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.