The Association of Vasomotor Symptoms with Thrombosis in Postmenopausal Women

描述（由申请人提供）：血管舒缩症状（VMS），定义为潮热和盗汗，大多数妇女在更年期过渡期间都会经历。除了影响生活质量外，流行病学证据表明，在一些女性中，VMS特征（严重程度、持续时间和时间）可能是与心血管风险（如中风和心肌梗死）相关的潜在生理变化的临床标志。VMS特征是否为促血栓形成状态的标志并与静脉血栓形成（VT）风险增加相关尚不清楚，但VT风险是这种性激素依赖性关联的极好候选表型。这项拟议的研究将通过分析妇女健康倡议（WHI- HT）激素治疗试验的现有数据，首次评估绝经后妇女VMS与血栓形成风险之间的关系。第一个目的是评估止血因子与VMS的存在及其严重程度、持续时间和时间之间的横断面关联。第二个目的是前瞻性地评估与VMS存在相关的临床VT风险及其严重程度、持续时间和时间。WHI-HT先前招募了27,347名年龄在50-79岁的绝经后妇女，并在基线时收集了有关VMS存在和严重程度的数据。在3个月的激素治疗（HT）洗脱期后，在任何HT随机化之前，WHI还收集了血液样本，其中测量了许多止血因子，如正常化活化蛋白C敏感性比（nAPCsr）、抗凝血酶（AT）、游离蛋白S和总蛋白S。VT事件由WHI研究人员使用标准化标准集中判定。为了解决目标1，将使用多元线性回归分别对VMS存在与每个止血因子的关联进行建模，并调整匹配变量和混杂因素。为了实现目标2，我们的主要分析将使用Cox比例风险模型评估基线VMS存在与到达vt事件（定义为PE或DVT）的时间之间的关系。我们提出的假设目前还没有被WHI调查，无论是在核心研究还是辅助研究中。了解VMS作为血栓形成风险的潜在标志物对临床实践和病因学的理解都具有重要意义。自我报告的VMS可以作为一种微创临床标志物，用于识别处于未被发现的中间血栓表型变化和潜在的VT和其他CVD事件风险增加的女性。将VMS作为血栓形成风险的潜在标志物进行评估，将进一步加深我们对VT的病因学和VMS生理学的理解，这两者都需要更好的表征。除了解决我们的具体目的外，这项拟议的研究将为阐明妇女血栓性疾病的病因所必需的未来研究提供新的证据。

DESCRIPTION (provided by applicant): Vasomotor symptoms (VMS), defined as hot flashes and night sweats, are experienced by the majority of women during the menopausal transition. In addition to impacting quality of life, epidemiologic evidence suggests that in some women, VMS characteristics (severity, duration, and timing) may be a clinical marker for underlying physiologic changes associated with cardiovascular risk, such as stroke and myocardial infarction. Whether VMS characteristics are a marker for a pro-thrombotic state and associated with an increased risk of venous thrombosis (VT) is not known, yet VT risk is an excellent candidate phenotype for such a sex-hormone dependent association. The proposed study will be the first to evaluate the association between VMS and thrombotic risk in postmenopausal women by analyzing existing data from the Women's Health Initiative (WHI- HT) Hormone Therapy trials. The first aim evaluates the cross-sectional association between hemostatic factors and the presence of VMS and its severity, duration, and timing. The second aim evaluates prospectively the risk of clinical VT associated with VMS presence and its severity, duration, and timing. The WHI-HT previously enrolled 27,347 postmenopausal women ages 50-79 years of age and at baseline, collected data regarding the presence and severity of VMS. Following a 3-month hormone therapy (HT) washout and prior to any randomization of HT, the WHI also collected blood samples in which a number of hemostatic factors, such as normalized activated protein C sensitivity ratio (nAPCsr), anti-thrombin (AT) and free and total protein S have been measured. VT events were centrally-adjudicated by WHI researchers using standardized criteria. To address aim 1, multiple linear regression will be used to model the association of VMS presence with each hemostatic factor, separately, adjusting for matching variables and confounders. To address aim 2, our primary analyses will assess the association of baseline VMS presence with time-to-VT event (defined as PE or DVT) using Cox Proportional Hazards models. The hypotheses we propose are not currently being investigated by WHI, either in core or ancillary studies. An understanding of VMS as a potential marker for thrombotic risk has important implications for both clinical practice and etiologic understanding. Self- reported VMS may serve as a minimally invasive clinical marker, useful for the identification of women experiencing undetected changes in intermediate thrombotic phenotypes and potentially at an increased risk of VT and other CVD events. An evaluation of VMS as a potential marker for thrombotic risk will further our understanding of both the etiology of VT as well as the physiology of VMS, both of which are in need of better characterization. In addition to addressing our specific aims, this proposed study will provide new evidence for future studies necessary to elucidate the etiology of thrombotic disease in women.