Langer Robert D, Pradhan Aruna D, Lewis Cora E, Manson JoAnn E, Rossouw Jacques E, Hendrix Susan L, LaCroix Andrea Z, Ridker Paul M
Department of Family and Preventive Medicine, University of California, San Diego, 9500 Gilman Drive, MC 0978, La Jolla, CA 92093-0978, USA.
Thromb Haemost. 2005 Jun;93(6):1108-16. doi: 10.1160/TH04-09-0608.
Clinical trials of postmenopausal hormone therapy (PHT) have found an early increase in cardiovascular events, and have not demonstrated the reduction in coronary heart disease (CHD) predicted from changes in conventional risk factors or found in observational studies, suggesting that PHT may increase coronary risk through other pathways. We compared baseline levels of C-reactive protein (CRP), interleukin-6 (IL-6), sICAM-1, tissue plasminogen activator antigen (tPA-antigen), D-dimer, homocysteine, triglycerides, total-, HDL- and LDL- cholesterol in 304 cases with incident CHD and 304 controls, according to self-reported use of PHT. Subjects were selected from the 75,343 participants in the WHI Observational Study without baseline cardiovascular disease or cancer. PHT was associated with higher CRP, HDL and triglycerides, and lower tPA-antigen and homocysteine. CRP was highest in users of unopposed conjugated equine estrogen. Levels of IL-6,sICAM-1,D-dimer and total cholesterol did not differ between PHT users and non-users. Transdermal estrogen users had low levels of D-dimer and CRP. Among users of estrogen plus progestin (EP), CRP, IL-6, tPA-antigen, D-dimer, total cholesterol and triglycerides were higher in women with incident coronary events than controls. Estrogen alone (E) controls shared only the tPA-antigen association, but had higher HDL and lower LDL than E cases. In non-users CRP, tPA-antigen and D-dimer were associated with incident CHD. In summary, risk markers differed by PHT category. Some associations differed between women with and without incident CHD, especially for EP, where inflammatory and thrombotic markers were higher in cases. These associations remain speculative pending confirmation in randomized trials.
绝经后激素治疗(PHT)的临床试验发现心血管事件早期增加,且未证明冠心病(CHD)的减少,这一减少是根据传统危险因素变化所预测或在观察性研究中发现的,提示PHT可能通过其他途径增加冠心病风险。我们根据自我报告的PHT使用情况,比较了304例冠心病患者和304例对照者的C反应蛋白(CRP)、白细胞介素-6(IL-6)、可溶性细胞间黏附分子-1(sICAM-1)、组织型纤溶酶原激活物抗原(tPA抗原)、D-二聚体、同型半胱氨酸、甘油三酯、总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇的基线水平。研究对象选自女性健康倡议(WHI)观察性研究的75343名参与者,这些参与者无基线心血管疾病或癌症。PHT与较高的CRP、高密度脂蛋白和甘油三酯相关,与较低的tPA抗原和同型半胱氨酸相关。未加对抗剂的结合马雌激素使用者的CRP最高。PHT使用者和非使用者之间的IL-6、sICAM-1、D-二聚体和总胆固醇水平无差异。经皮雌激素使用者的D-二聚体和CRP水平较低。在雌激素加孕激素(EP)使用者中,发生冠心病事件的女性的CRP、IL-6、tPA抗原、D-二聚体、总胆固醇和甘油三酯高于对照组。单用雌激素(E)的对照组仅存在tPA抗原相关性,但高密度脂蛋白高于E组病例,低密度脂蛋白低于E组病例。在非使用者中,CRP、tPA抗原和D-二聚体与冠心病事件相关。总之,风险标志物因PHT类别而异。有和没有冠心病事件的女性之间的一些相关性有所不同,尤其是对于EP,病例中的炎症和血栓形成标志物较高。在随机试验得到证实之前,这些相关性仍属推测。