The Association of Vasomotor Symptoms with Thrombosis in Postmenopausal Women

描述（由申请人提供）：血管痉挛症状（VMS），定义为潮热和盗汗，大多数女性在绝经过渡期都会经历。除了影响生活质量外，流行病学证据表明，在某些女性中，VMS特征（严重程度，持续时间和时间）可能是与心血管风险相关的潜在生理变化的临床标志物，如中风和心肌梗死。VMS特征是否是血栓前状态的标志物并与静脉血栓形成（VT）风险增加相关尚不清楚，但VT风险是这种性激素依赖性相关性的极好候选表型。这项研究将是第一个通过分析妇女健康倡议（WHI-HT）激素治疗试验的现有数据来评估VMS与绝经后妇女血栓形成风险之间的关联的研究。第一个目的是评价止血因子与VMS的存在及其严重程度、持续时间和时间之间的横截面相关性。第二个目标是前瞻性评价与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岁之间的绝经后女性，并在基线时收集了有关VMS存在和严重程度的数据。在3个月激素治疗（HT）洗脱后和任何HT随机化之前，WHI还采集了血液样本，其中测量了许多止血因子，如标准化活化蛋白C敏感性比（nAPCsr）、抗凝血酶（AT）以及游离和总蛋白S。VT事件由WHI研究人员使用标准化标准集中裁定。为了解决目标1，将使用多元线性回归分别对VMS存在与每种止血因素的相关性进行建模，并对匹配变量和混杂因素进行调整。为了解决目标2，我们的主要分析将使用考克斯比例风险模型评估基线VMS存在与至VT事件（定义为PE或DVT）时间的相关性。我们提出的假设目前还没有被WHI研究，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理解具有重要意义。自我报告的VMS可作为微创临床标志物，可用于鉴定经历未检测到的中间血栓形成表型变化以及VT和其他CVD事件风险可能增加的女性。VMS作为血栓形成风险的潜在标志物的评价将进一步加深我们对VT的病因学以及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，这项拟议中的研究将提供新的证据，为未来的研究，阐明血栓性疾病的病因在妇女。

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.