女性健康倡议激素治疗试验中冠心病风险的炎症、脂质、血栓形成及遗传标志物。
Inflammatory, lipid, thrombotic, and genetic markers of coronary heart disease risk in the women's health initiative trials of hormone therapy.
作者信息
Rossouw Jacques E, Cushman Mary, Greenland Philip, Lloyd-Jones Donald M, Bray Paul, Kooperberg Charles, Pettinger Mary, Robinson Jennifer, Hendrix Susan, Hsia Judith
机构信息
Women's Health Initiative Branch, Division of Prevention and Population Sciences, National Heart, Lung, and Blood Institute, 6701 Rockledge Dr, Rockledge 2 Bldg, Ste 10018, Bethesda, MD 20892, USA.
出版信息
Arch Intern Med. 2008 Nov 10;168(20):2245-53. doi: 10.1001/archinte.168.20.2245.
BACKGROUND
Clinical trials of postmenopausal hormone therapy (HT) have shown increased risk of coronary heart disease (CHD) in the first few years after initiation of therapy and no overall benefit.
METHODS
This nested case-control study evaluates a range of inflammatory, lipid, thrombotic, and genetic markers for their association with CHD in the 4 years after randomization and assesses whether any of these markers modified or mediated the initially increased risk associated with HT in postmenopausal women aged 50 to 79 years at baseline. Conjugated equine estrogens, 0.625 mg/d, or placebo was given to 10 739 hysterectomized women, and the same estrogen plus medroxyprogesterone acetate, 2.5 mg/d, was given to 16 608 women with an intact uterus.
RESULTS
In multivariate-adjusted analyses of 359 cases and 820 controls in the combined trials, baseline levels of 12 of the 23 biomarkers studied were associated with CHD events: interleukin 6, matrix metalloproteinase 9, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides, D-dimer, factor VIII, von Willebrand factor, leukocyte count, homocysteine, and fasting insulin. Biomarkers tended to be more strongly associated with CHD in the initial 2 years after randomization. The genetic polymorphism glycoprotein IIIa leu33pro was significantly associated with CHD. Baseline low-density lipoprotein cholesterol interacted significantly with HT so that women with higher levels were at higher risk for CHD when given HT (P = .03 for interaction). The levels of several biomarkers were changed by HT, but these changes did not seem to be associated with future CHD events.
CONCLUSIONS
Several thrombotic, inflammatory, and lipid biomarkers were associated with CHD events in postmenopausal women, but only low-density lipoprotein cholesterol modified the effect of HT. Further research is needed to identify the mechanisms by which HT increases the risk of CHD.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00000611.
背景
绝经后激素治疗（HT）的临床试验表明，治疗开始后的头几年冠心病（CHD）风险增加，且无总体益处。
方法
这项巢式病例对照研究评估了一系列炎症、血脂、血栓形成和基因标志物在随机分组后4年内与冠心病的关联，并评估这些标志物是否改变或介导了基线时年龄在50至79岁的绝经后女性中与HT相关的初始风险增加。对10739名子宫切除的女性给予0.625mg/d的结合马雌激素或安慰剂，对16608名子宫完整的女性给予相同的雌激素加2.5mg/d的醋酸甲羟孕酮。
结果
在联合试验中对359例病例和820例对照进行的多变量调整分析中，所研究的23种生物标志物中有12种的基线水平与冠心病事件相关：白细胞介素6、基质金属蛋白酶9、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、总胆固醇、甘油三酯、D-二聚体、凝血因子VIII、血管性血友病因子、白细胞计数、同型半胱氨酸和空腹胰岛素。生物标志物在随机分组后的最初2年中往往与冠心病的关联更强。基因多态性糖蛋白IIIa leu33pro与冠心病显著相关。基线低密度脂蛋白胆固醇与HT有显著交互作用，因此给予HT时，水平较高的女性患冠心病的风险更高（交互作用P = 0.03）。几种生物标志物的水平因HT而改变，但这些改变似乎与未来的冠心病事件无关。
结论
几种血栓形成、炎症和血脂生物标志物与绝经后女性的冠心病事件相关，但只有低密度脂蛋白胆固醇改变了HT的作用。需要进一步研究以确定HT增加冠心病风险的机制。
试验注册
clinicaltrials.gov标识符：NCT00000611。
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