Modifiable risk factors in stroke incidence and mortality among women

描述（由申请人提供）：中风是美国第三大死亡原因，女性占中风死亡人数的60%。在过去的十年中，可改变暴露的主要变化——肥胖和缺乏运动的增加以及绝经期激素治疗（MHT）使用的减少——正在改变女性的健康状况，但它们对女性中风的影响尚不清楚。加州教师研究（CTS）是一项前瞻性队列研究，自1995年以来积极跟踪133,479名加州公立学校女性专业人员的广泛健康结果，准备评估这些可改变暴露的社会转变如何影响中风的发病率和死亡率。CTS队列中关于可改变危险因素的生命过程暴露数据的独特存储库为与长期体育活动史、体脂分布的纵向人体测量数据和详细的MHT使用相关的妇女健康风险的前瞻性评估提供了近乎单一的资源。我们的具体目标是研究这些变化暴露对中风发病率和死亡率的影响，无论是单独的还是共同的，无论是总体的还是两种主要中风亚型（缺血性和出血性）。在目的1中，我们将确定肥胖和缺乏运动对发生率、风险和人口归因比例的影响。我们详细的问卷调查使我们能够评估终身和不断变化的肥胖表型模式（定义为总体肥胖的时间变化与成人体脂分布的结合）和身体活动的影响，包括年龄和近期。在目标2中，我们将确定肥胖和缺乏身体活动（目标1）对发病率、风险和人群归因比例的影响是否在广泛停止使用MHT后（2002年之后）变得更加明显。为了实现这些目标，我们将计算按2000年美国人口标准调整的年龄和特定年龄的年发病率和死亡率。为了计算风险关联，我们将使用从青少年到老年这些关键暴露的时间依赖暴露数据，并使用统计方法分析与中风风险和死亡率的关联，这些方法可以解释数据缺失和暴露的长期变化。我们将计算每个病因危险因素的人口归因比例，并按MHT广泛使用的时间段与最近使用急剧下降的时间段进行计算。公共卫生相关性：成功完成这些目标将能够评估十年来肥胖、身体活动和MHT使用对妇女中风发病率和死亡率的深刻转变对人口的影响，并深入了解这些与其他相关暴露之间的相互作用。这一建议侧重于中风发病的病因学和中风死亡的原因，并强调常见的、可改变的、行为的危险因素，这些因素可以促进未来全人群的中风预防工作。

DESCRIPTION (provided by applicant): Stroke is the third leading cause of death in the United States (U.S.) and women account for 60% of all deaths from stroke. Major shifts in modifiable exposures over the past decade - increasing obesity and physical inactivity and decreasing menopausal hormone therapy (MHT) use - are changing the profile of women's health, but their effect on stroke among women is unclear. The California Teachers Study (CTS), a prospective cohort study that has actively followed 133,479 female California public school professionals for a broad range of health outcomes since 1995, is poised to evaluate how these societal transitions in modifiable exposures affect incidence of and mortality from stroke. The unique repository of life course exposure data on modifiable risk factors in the CTS cohort provides a near-singular resource for prospective assessment of women's health risks associated with long-term history of physical activity, longitudinal anthropometry data on body fat distribution, and detailed MHT use. Our specific aims address the impact of these shifting exposures both individually and together on stroke incidence and mortality, both overall and among the two major stroke subtypes (ischemic and hemorrhagic). In Aim 1, we will determine the impact of obesity and physical inactivity on the rates, risk, and population attributable fraction of incident and fatal stroke. Our detailed questionnaires permit us to evaluate the effect of lifelong and changing patterns of obesity phenotypes (defined as a combination of temporal changes in overall adiposity with adult body fat distribution) and physical activity, including by age and recency. In Aim 2, we will determine whether the effects on rates, risk and population attributable fraction observed from obesity and physical inactivity (Aim 1) become more pronounced in the years following widespread cessation of MHT use (after 2002). To accomplish these aims, we will calculate age-adjusted and age-specific annual incidence and mortality rates, standardized to the U.S. population in 2000. To calculate risk associations, we will use time-dependent exposure data on these key exposures from teenage years to old age and analyze associations with stroke risk and mortality using statistical approaches that account for missing data and secular changes in exposures. We will calculate the population attributable fraction for each etiologic risk factor, and by time period when MHT was widely used versus the recent sharp decline in use. Public Health Relevance: Successful completion of these aims will permit evaluation of the population impact of a decade of profound transition in obesity, physical activity, and MHT use on women's stroke incidence and mortality, and provide insight into the interplay between these and other relevant exposures. This proposal focuses on the etiology of stroke incidence and causes of stroke mortality and emphasizes common, modifiable, behavioral risk factors in ways that can facilitate future population-wide stroke prevention efforts. PUBLIC HEALTH RELEVANCE: The California Teachers Study spans more than a decade of profound transitions in women's health behaviors, including increasing physical inactivity and obesity, and decreasing use of hormone therapy. By examining how exposures to these common, modifiable risk factors over a woman's lifespan influences rates and risk of stroke incidence and mortality, this study will provide critical new knowledge that can serve as the basis for behavioral public health interventions that benefit women on a population-wide scale.