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：

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循环 SHBG（性激素结合球蛋白）和缺血性中风的风险：来自 WHI 的发现。


背景和目的 - SHBG（性激素结合球蛋白）的循环水平与肥胖、糖尿病和其他心脏代谢疾病呈负相关。目前尚不确定低性激素结合球蛋白（SHBG）是否可以前瞻性地预测中风风险，尤其是女性。我们调查了性激素结合球蛋白 (SHBG) 是否与 WHI（女性健康倡议）女性中发生缺血性中风 (IS) 的风险相关。方法 - 从 1993 年至 1998 年在美国 40 个地点参加 WHI 的 161 808 名绝经后妇女的观察队列中，我们确定了 13 192 名基线时没有流行中风的参与者，她们被纳入一项测量血清 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 SHBG 五分位数（Q1-Q5）的 IS 风险，首先调整人口变量（模型 1），另外调整体重指数、高血压、饮酒和吸烟状态（模型 2），以及体力活动和生殖风险因素（模型 3）。在敏感性分析中，包括了潜在的调节因素（糖尿病状态、雌二醇、睾酮水平和 CRP [C 反应蛋白]）。结果 - 在 13 192 名参与者（平均年龄 62.5 岁；67.4% 非西班牙裔白人、18.5% 黑人、7.6% 西班牙裔和 5.0% 亚裔）中，经过平均 11.6 年的跟踪，共裁定了 768 起 IS 事件。与 SHBG 水平最高五分位数（参考）相比，处于最低 SHBG 五分位数的女性在所有 3 个多变量模型中具有较高的 IS 风险（模型 1：风险比，1.88 [95% CI，1.47-2.41]；模型 2：风险比，1.69 [95% CI，1.30-2.20]；模型 3：风险比，1.61 [95% CI，1.19-2.19]；所有模型的趋势检验 P<0.05）。 在模型中加入糖尿病、雌二醇和睾酮等潜在介质会减弱但并未消除 SHBG 与 IS 之间的显着负相关。结论-在绝经后女性的前瞻性队列中，血清 SHBG 水平与 IS 风险之间存在统计学上显着的负相关，这支持了 SHBG 可用作预测女性 IS 风险分层工具的观点。