Subclinical Thyroid Dysfunction & Risk of MI and Stroke

描述(申请人提供)：心血管疾病，包括心肌梗死(MI)和中风，是美国女性的主要死亡原因。亚临床甲状腺功能减退症(SCH)，即甲状腺激素水平在正常范围内，但促甲状腺激素(TSH)升高，已被认为与血脂异常、动脉粥样硬化和心肌梗死有关。然而，文献很少，证据受到小规模研究的限制，许多是横断面设计。美国预防服务工作组和医学研究所最近都得出结论，目前的数据不足以为临床决策提供有关SCH筛查或治疗的必要性的信息。因为SCH在女性中更常见，而且随着年龄的增加，我们试图在一大批绝经后女性的前瞻性队列中检查SCH与MI和中风风险的相关性。我们建议在妇女健康倡议的93,676名成员的观察性研究中进行有效的病例队列研究，包括800名经历过心肌梗死的女性，750名血栓/栓塞性中风患者，以及随机选择的3200名在年龄、种族/民族和临床中心密度匹配的女性亚队列。参与者有广泛的基线人口统计、健康、行为和体检数据，并有存储的血清可用。我们将测量TSH和甲状腺激素水平，以便在入院时确定SCH。后续行动包括每年更新健康状况和在第三年进行体检；所有妇女自登记以来已超过5年或相当于5年。因此，使用新的实验室研究和现有的WHI数据，我们将能够回答这些主要的研究问题：在没有甲状腺疾病、心肌梗死或中风病史的女性中：1)基线上的亚临床甲状腺功能减退是否与心肌梗死的风险独立相关？2)基线上的亚临床甲状腺功能减退是否与缺血性中风的风险独立相关3)什么形式的关联最好地描述了TSH作为一种连续指标与心肌梗死和中风的风险之间的关系？4)SCH的人群相关性(即种族/民族、BMI、激素治疗、共病)是什么？这些信息--目前中老年妇女无法获得--与公共卫生和保健政策密切相关，以确定与SCH相关的疾病负担，并量化最终人口筛查和治疗的益处和成本。

DESCRIPTION (provided by applicant): Cardiovascular disease, including myocardial infarction (MI) and stroke, is the leading cause of death for women in the United States. Subclinical hypothyroidism (SCH), in which thyroid hormone levels are in the normal range but thyroid stimulation hormone (TSH) is elevated, has been linked to abnormal lipid profiles, atherosclerosis, and MI. The literature is scant however, and the evidence constrained by small studies, many of cross-sectional design. Both the US Preventive Services Task Force and the Institute of Medicine recently concluded that current data are insufficient to inform clinical decision-making about the need for screening or treatment for SCH. Because SCH is more common among women and with advancing age, we seek to examine the association of SCH and risk of MI and stroke in a large prospective cohort of post-menopausal women. We propose an efficient case-cohort study within the 93,676-member Observational Study of the Women's Health Initiative, including 800 women who have experienced an MI, 750 with thrombotic/embolic stroke, and a randomly selected subcohort of 3,200 women density-matched for age, race/ethnicity, and clinical center. Participants have extensive baseline demographic, health, behavioral, and physical exam data and stored serum available. We will measure TSH and thyroid hormone levels in order to identify SCH at entry. Follow-up includes annual health status updates and a physical exam in the third year; more than or equal to 5 years have passed since enrollment for all women. Thus, using new laboratory studies and existing WHI data, we will be able to answer these primary research questions: Among women without a history of thyroid disease, MI, or stroke: 1) Is subclinical hypothyroidism at baseline independently associated with risk of MI? 2) Is subclinical hypothyroidism at baseline independently associated with risk of ischemic stroke 3) What form of association best describes the relationship between TSH, as a continuous measure, and risk of MI and stroke? 4) What are the population correlates (i.e., race/ethnicity, BMI, hormone therapy, comorbidity) of SCH? This information - currently unavailable for middle-aged and older women - is germane to public health and health care policy to define the burden of illness associated with SCH, and to quantify the benefits and costs of eventual population screening and treatment.