Background and Purpose- Circulating levels of SHBG (sex hormone-binding globulin) have been inversely linked to obesity, diabetes mellitus, and other cardiometabolic disorders. It remains uncertain whether low SHBG is prospectively predictive of stroke risk, particularly in women. We investigated whether SHBG is associated with risk of incident ischemic stroke (IS) among women in the WHI (Women's Health Initiative). Methods- From an observational cohort of 161 808 postmenopausal women enrolled in the WHI at 40 sites across the United States from 1993 to 1998, we identified 13 192 participants free of prevalent stroke at baseline who were included in an ancillary study that measured serum SHBG. We used Cox proportional hazards regression, stratified by SHBG measurement assay, to assess IS risk across quintiles of SHBG (Q1-Q5), adjusting first for demographic variables (model 1), additionally for body mass index, hypertension, alcohol use, and smoking status (model 2), and for physical activity and reproductive risk factors (model 3). In sensitivity analyses, potential mediators (diabetes mellitus status, levels of estradiol, testosterone, and CRP [C-reactive protein]) were included. Results- Of 13 192 participants (mean age, 62.5 years; 67.4% non-Hispanic white, 18.5% black, 7.6% Hispanic, and 5.0% Asian), after following for an average of 11.6 years, 768 IS events were adjudicated. Compared with the highest quintile of SHBG levels (referent), women in the lowest SHBG quintile had a higher risk of IS in all 3 multivariable models (model 1: hazard ratio, 1.88 [95% CI, 1.47-2.41]; model 2: hazard ratio, 1.69 [95% CI, 1.30-2.20]; model 3: hazard ratio, 1.61 [95% CI, 1.19-2.19]; trend tests P<0.05 for all models). Including potential mediators such as diabetes mellitus, estradiol, and testosterone in the models attenuated but did not eliminate significant inverse associations between SHBG and IS. Conclusions- In this prospective cohort of postmenopausal women, there was a statistically significant inverse association between serum SHBG levels and IS risk, which supports the notion that SHBG could be used as a risk stratification tool for predicting IS in women.

中文翻译：

---

循环性SHBG（性激素结合球蛋白）与缺血性中风的风险：WHI的发现。

背景和目的-循环中的SHBG（性激素结合球蛋白）水平与肥胖症，糖尿病和其他心脏代谢疾病呈负相关。尚不确定低SHBG是否可预测卒中风险，特别是在女性中。我们调查了WHI（妇女健康倡议）中女性的SHBG是否与发生缺血性中风（IS）的风险有关。方法-从1993年至1998年在美国40个地区的WHI入组的161808名绝经后妇女的观察性队列中，我们确定了13192名基线时无中风的参与者，这些参与者参加了一项测量血清SHBG的辅助研究。我们使用Cox比例风险回归（通过SHBG测量分析进行分层）来评估五分之一个的SHBG（Q1-Q5）的IS风险，首先针对人口统计学变量（模型1）进行调整，另外针对体重指数，高血压，饮酒和吸烟状况（模型2）进行调整，并针对体育活动和生殖危险因素（模型3）进行调整。在敏感性分析中，包括潜在的介体（糖尿病状态，雌二醇，睾丸激素和CRP [C反应蛋白]）。结果-在平均平均11.6年之后，对13 192名参与者（平均年龄62.5岁；非西班牙裔白人67.4％，非西班牙裔白人18.5％，西班牙裔7.6％和亚洲裔5.0％）进行了裁决，共判定768次IS事件。与SHBG水平最高的五分位数（参考）相比，SHBG五分位数最低的女性在所有3个多变量模型中均具有较高的IS风险（模型1：危险比，1.88 [95％CI，1.47-2.41]；模型2：危险比1.69 [95％CI，1.30-2.20];模型3：危险比1.61 [95％CI，1。19-2.19]; 所有模型的趋势测试P <0.05）。模型中包括糖尿病，雌二醇和睾丸激素等潜在介体的作用减弱但并未消除SHBG与IS之间的显着逆相关。结论：在这个绝经后妇女的前瞻性队列中，血清SHBG水平与IS风险之间存在统计学上的显着负相关，这支持了SHBG可以用作预测妇女IS的风险分层工具的观点。