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

中老年女性的累积压力和心血管疾病风险

• 批准号: 9043982
• 负责人: Michelle A Albert
• 金额: $ 36.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9043982
• 关键词: Cumulative; Stress; CVD; Risk; Middle

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.

描述（由申请人提供）：我们建议通过利用女性健康研究（WHS）的参与者对累积压力对心血管疾病风险的影响进行成本效益检查，该研究是一组最初健康的女性健康专业人员，迄今已有15年的心血管疾病随访。实验和流行病学研究表明，单一领域的急性终身压力，如工作压力增加心血管疾病的风险，但数据的一般感知压力或复合措施的不同领域的压力随着时间的推移是缺乏的。这些研究受到样本量相对较小、测量心血管疾病或缺血性心脏病或死亡率的替代指标的限制，结果不一，而且中年或老年妇女很少。WHS于1992年启动，在39876名年龄在45岁或以上的女性健康专业人员中进行了阿司匹林和维生素E在癌症和心血管疾病一级预防中的随机试验。该试验于2004年结束，经过平均10年的观察性随访，每年提供风险因素和终点信息，迄今为止发病率和死亡率随访率分别至少为90%和100%。超过28，000名参与者提供了人口统计学和临床信息以及随机化前的血液样本，从而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，在没有额外成本的情况下，WHS提供了利用机制驱动的生理应激假设来鉴定与累积应激和CVD风险相关的潜在基因，这是一个几乎不存在研究的领域。因此，拟议的研究将在WHS的25，000名中年和老年女性参与者中进行，这些参与者具有广泛的人口统计学，生活方式，临床和GWAS信息。我们寻求资金发送邀请函，压力问卷包括与这项拟议的5年研究的第1年和第3年的急性和慢性终身压力源（累积压力）相关的问题，并通过病历审查评估事件CVD风险因素（体重变化，II型糖尿病，高血压）和CVD结局（心肌梗死，卒中，冠状动脉血运重建和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中的成功，以及我们在这一人群中初步压力和社会经济相关数据的证据，我们相信，这项提案将通过评估生活中可能发生的多个压力领域的个体和综合影响，社会和心理调节剂对后者的影响，使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CVD结果的潜在作用。因此，这项拟议的研究将提供有价值的临床信息，可以导致行为和治疗干预措施的发展，旨在减少累积压力对CVD健康的影响。