The Association of Vasomotor Symptoms with Thrombosis in Postmenopausal Women

描述(申请人提供)：血管运动症状(VMS)，定义为潮热和盗汗，大多数妇女在更年期过渡期间经历。除了影响生活质量，流行病学证据表明，在一些女性中，VMS的特征(严重性、持续时间和时机)可能是与心血管风险相关的潜在生理变化的临床标志，如中风和心肌梗死。目前尚不清楚VMS特征是否是血栓前状态的标志，并与静脉血栓形成(VT)风险增加相关，但VT风险是这种性激素依赖关系的极佳候选表型。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VMS与绝经后妇女血栓形成风险之间的联系。第一个目的是评估止血因素与VMS的存在及其严重程度、持续时间和时机之间的横断面关联。第二个目的是前瞻性地评估与VMS存在相关的临床VT的风险及其严重性、持续时间和时机。WHI-HT之前招募了27,347名年龄在50-79岁之间的绝经后妇女，收集了关于VMS的存在和严重程度的数据。在激素治疗3个月后，在激素治疗随机进行之前，WHI还采集了一些止血因子，如归一化激活蛋白C敏感性比(NAPCsr)、抗凝血酶(AT)、游离和总蛋白S。室性心动过速事件由WHI研究人员使用标准化标准进行集中评判。为了解决目标1，将使用多元线性回归分别对VMS存在与每个止血因素的关联进行建模，调整匹配变量和混杂因素。为了达到目标2，我们的初步分析将使用COX比例风险模型评估基线VMS存在与VT发生时间(定义为PE或DVT)之间的关联。我们提出的假设目前没有得到WHI的调查，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记物对于临床实践和病因学理解都具有重要意义。自我报告的VMS可作为一种微创的临床标志物，有助于识别经历未被检测到的中间血栓表型变化的妇女，并有可能增加VT和其他CVD事件的风险。对VMS作为血栓风险的潜在标志物的评估将加深我们对VT的病因和VMS的生理学的理解，这两者都需要更好的表征。除了解决我们的具体目标，这项拟议的研究将为未来必要的研究提供新的证据，以阐明女性血栓性疾病的病因学。

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.