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

描述(由申请者提供)：我们建议利用女性健康研究(WHS)的参与者，对累积压力对心血管疾病风险的影响进行具有成本效益的检查。WHS是一组最初健康的女性健康专业人员，迄今已对心血管疾病进行了15年的随访。实验和流行病学研究表明，急性生活压力的单一领域，如工作压力，会增加心血管疾病的风险，但缺乏关于总体感知压力或不同压力领域随时间的综合衡量的数据。这类研究受限于相对较小的样本量，衡量心血管疾病或缺血性心脏病的替代者或死亡率作为结果，结果喜忧参半，中年或老年女性很少。WHS于1992年启动，是一项阿司匹林和维生素E在癌症和心血管疾病一级预防中的随机试验，对象是年龄在45岁或以上的39,876名女性卫生专业人员。这项试验于2004年结束，平均为期10年，并进行了年度风险因素和终点信息的观察性随访，到目前为止，发病率和死亡率分别至少为90%和100%。28,000名参与者提供了人口统计和临床信息以及预随机化的血液样本，使冷冻样本得以长期存储并进行全基因组关联扫描(GWAS)。因此，这一队列提供了一个宝贵而独特的机会，可以利用高质量的人口统计学和心血管疾病终点数据来检查个人和累积应激源对心血管疾病风险的影响。此外，WHS在不增加成本的情况下，利用机制驱动的生理应激假说识别与累积应激和心血管疾病风险相关的潜在基因，这是一个几乎不存在的研究领域。因此，这项拟议的研究将在WHS的25,000名中老年女性参与者中进行，她们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，在这项拟议的5年研究的第1年和第3年发出邀请函，包括与急性和慢性生活应激源(累积应激)相关的问题的压力问卷，并通过病历回顾评估发生心血管疾病的危险因素(体重变化、II型糖尿病、高血压)和心血管疾病结局(心肌梗死、中风、冠状动脉血运重建和心血管疾病死亡)。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，以及来自我们在这一人群中的初步应激和社会经济相关数据的证据，我们相信这项建议将通过评估生活中可能发生的多个应激领域的个人和综合影响，社会和心理介质对后者的影响，使用创新的统计分析和探索性分析来检查与生理应激途径相关的基因对心血管疾病结局的潜在作用，从而促进对应激在心血管健康中作用的认识。因此，这项拟议的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.