Cushman M, Costantino J P, Tracy R P, Song K, Buckley L, Roberts J D, Krag D N
Department of Medicine and Pathology, University of Vermont, Burlington 05446, USA.
Arterioscler Thromb Vasc Biol. 2001 Feb;21(2):255-61. doi: 10.1161/01.atv.21.2.255.
-Tamoxifen reduces the incidence of breast cancer in women at risk for that disease. Because heart disease is the leading cause of death in women and because tamoxifen is also associated with venous thrombosis, an improved understanding of the association of tamoxifen with cardiovascular disease risk factors is required. In 111 healthy women at a single center, who were participating in a randomized double-blind breast cancer prevention trial, the 6-month effects of oral tamoxifen (20 mg/d) compared with placebo on factors related to inflammation, hemostasis, and lipids were studied. Tamoxifen was associated with reductions of 26% in median C-reactive protein, 22% in median fibrinogen, and 9% in cholesterol (all P:<0.01 compared with placebo). There were no differences in treatment effects on factor VII coagulant activity, fragment 1-2, and triglycerides. In secondary analyses, the effect of tamoxifen on C-reactive protein was larger in postmenopausal women and in women with higher waist-to-hip ratios. The effect on fibrinogen was larger in women with higher baseline cholesterol. Tamoxifen demonstrated effects on inflammatory markers that were consistent with reduced cardiovascular risk. These findings are in contrast to recent reports of increased C-reactive protein associated with postmenopausal estrogen. The potential for beneficial cardiovascular effects of tamoxifen in healthy women is suggested.
他莫昔芬可降低有患乳腺癌风险女性的乳腺癌发病率。由于心脏病是女性的主要死因,且他莫昔芬还与静脉血栓形成有关,因此需要更好地了解他莫昔芬与心血管疾病风险因素之间的关联。在一个单一中心的111名健康女性中,她们参与了一项随机双盲乳腺癌预防试验,研究了口服他莫昔芬(20毫克/天)与安慰剂相比,对炎症、止血和脂质相关因素的6个月影响。他莫昔芬使C反应蛋白中位数降低26%,纤维蛋白原中位数降低22%,胆固醇降低9%(与安慰剂相比,所有P值均<0.01)。在对凝血因子VII促凝活性、1-2片段和甘油三酯的治疗效果上没有差异。在二次分析中,他莫昔芬对C反应蛋白的影响在绝经后女性和腰臀比更高的女性中更大。对纤维蛋白原的影响在基线胆固醇水平较高的女性中更大。他莫昔芬对炎症标志物的影响与降低心血管风险一致。这些发现与最近关于绝经后雌激素与C反应蛋白升高相关的报道形成对比。提示他莫昔芬对健康女性可能具有有益的心血管作用。