Cumulative Stress and CVD Risk in Middle-Aged and Older Women

描述（由申请人提供）：我们建议利用妇女健康研究（WHS）的参与者进行一项具有成本效益的累积压力对心血管疾病风险影响的研究，WHS是一组最初健康的女性卫生专业人员，迄今为止进行了15年的心血管疾病随访。实验和流行病学研究表明，单一领域的急性生活压力（如工作压力）会增加心血管疾病的风险，但缺乏关于一般感知压力或不同领域压力随时间变化的综合测量的数据。这类研究的局限性在于样本量相对较小，测量的心血管疾病或缺血性心脏病或死亡率的替代指标结果混杂，而且很少有中年或老年妇女。WHS于1992年启动，是一项针对39,876名年龄在45岁或以上的女性卫生专业人员的阿司匹林和维生素E初级预防癌症和心血管疾病的随机试验。该试验于2004年结束，平均随访10年，每年随访危险因素和终点信息，迄今分别有至少90%和100%的发病率和死亡率随访。人口统计学和临床信息以及预随机化血液样本由bbb28,000名参与者提供，能够长期储存冷冻样本并进行全基因组关联扫描（GWAS）。因此，该队列提供了一个宝贵而独特的机会，利用高质量的人口统计学和CVD终点数据来检查个体和累积压力源对CVD风险的影响。此外，在没有额外费用的情况下，WHS可以利用机制驱动的生理应激假设来识别与累积应激和心血管疾病风险相关的潜在基因，这一领域的研究实际上是不存在的。因此，拟议的研究将在25,000名WHS的中老年妇女参与者中进行，这些妇女拥有广泛的人口统计、生活方式、临床和GWAS信息。我们寻求资金来发送邀请函，压力问卷，包括在这项拟议的5年研究的第1年和第3年与急性和慢性终生压力源（累积压力）相关的问题，并通过医疗记录审查评估CVD事件危险因素（体重变化，II型糖尿病，高血压）和CVD结局（心肌梗死，中风，冠状动脉血管重建化和CVD死亡）。鉴于我们在WHS和其他基于邮件的临床试验和队列研究方面的成功，以及我们在这一人群中获得的初步压力和社会经济相关数据的证据，我们相信，通过评估生活中可能发生的多领域压力的个体和综合影响，以及社会和心理介质对后者的影响，这一提议将推进对压力在心血管健康中的作用的认识。利用创新的统计分析和探索性分析，研究与生理应激途径相关的基因对心血管疾病结果的潜在作用。因此，本研究将提供有价值的临床信息，有助于开发旨在减少累积应激源对心血管疾病健康影响的行为和治疗干预措施。

DESCRIPTION (provided by applicant): We propose to conduct a cost-effective examination of the influence of cumulative stress on cardiovascular disease risk by utilizing participants from the Women's Health Study (WHS), a cohort of initially healthy female health professionals with 15 years of cardiovascular disease follow-up thus far. Experimental and epidemiologic studies suggest that single domains of acute lifetime stress such as job stress increase CVD risk, but data about general perceived stress or composite measures of different domains of stress over time are lacking. Such studies are limited by relatively small sample sizes, measurement of surrogates of CVD or ischemic heart disease or mortality as outcomes with mixed findings and have few middle-aged or older women. The WHS was initiated in 1992 as a randomized trial of aspirin and vitamin E in the primary prevention of cancer and cardiovascular disease among 39, 876 female health professionals aged 45 years or older. The trial concluded in 2004 after a mean of 10 years and observational follow-up with yearly risk factor and endpoint information with at least 90% and 100% morbidity and mortality follow-up respectively to date. Demographic and clinical information as well as pre-randomization blood samples have been provided by >28,000 participants enabling long term storage of frozen samples and conduct of a whole genome association scan (GWAS). Accordingly, this cohort provides a precious and unique opportunity to utilize high-quality demographic and CVD endpoint data to examine the impact of individual and cumulative stressors on CVD risk. Moreover, at no additional cost, WHS affords the identification of potential genes associated with cumulative stress and CVD risk utilizing mechanism driven physiologic stress hypotheses, an area where research is practically non-existent. Therefore, the proposed study will be conducted among 25,000 middle-aged and older women participants of the WHS who have extensive demographic, lifestyle, clinical and GWAS information. We seek funds to send an invitation letter, stress questionnaire comprised of questions related to acute and chronic lifetime stressors (cumulative stress) at years 1 and 3 of this proposed 5 year study and to evaluate incident CVD risk factors (weight change, type II diabetes, hypertension) and CVD outcomes (myocardial infarction, stroke, coronary revascularization and CVD death) by medical record review. Given our success with WHS and other mail-based clinical trials and cohort studies, as well as the evidence from our preliminary stress and socioeconomic related data in this population, we believe that this proposal will advance the knowledge of the role of stress in cardiovascular health by evaluating the individual and composite impact of multiple domains of stress that can occur during life, the influence of social and psychological mediators on the latter, use of innovative statistical analyses and in exploratory analyses examine the potential role of genes linked to physiologic stress pathways on CVD outcome. Thus, this proposed study will provide valuable clinical information that can result in the development of behavioral and therapeutic interventions aimed at decreasing the effects of cumulative stressors on CVD health.