From the Department of Emergency Medicine (T.E.M.), Alpert Medical School of Brown University, Providence, RI.
Department of Biostatistics and Data Science, The University of Texas Health Science Center at Houston (X.L.).
Stroke. 2020 Apr;51(4):1257-1264. doi: 10.1161/STROKEAHA.120.028905. Epub 2020 Feb 12.
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 <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.
背景与目的-循环中的 SHBG（性激素结合球蛋白）水平与肥胖、糖尿病和其他心血管代谢疾病呈负相关。目前尚不确定低 SHBG 是否与卒中风险有前瞻性关联，尤其是在女性中。我们研究了 WHI（妇女健康倡议）中的女性中，SHBG 是否与缺血性卒中（IS）的发病风险相关。
方法-从美国 40 个地点 1993 年至 1998 年参加 WHI 的 161808 名绝经后妇女的观察队列中，我们确定了 13192 名基线时无明显卒中的参与者，这些参与者纳入了一项测量血清 SHBG 的辅助研究。我们使用 Cox 比例风险回归，按 SHBG 测定分析分层，评估 SHBG（Q1-Q5）五分位数的 IS 风险，首先调整人口统计学变量（模型 1），其次调整体重指数、高血压、饮酒和吸烟状况（模型 2），最后调整体力活动和生殖风险因素（模型 3）。在敏感性分析中，纳入了潜在的中介因素（糖尿病状态、雌二醇、睾酮和 CRP[C 反应蛋白]水平）。
结果-在 13192 名参与者中（平均年龄 62.5 岁；67.4%为非西班牙裔白人，18.5%为黑人，7.6%为西班牙裔，5.0%为亚裔），平均随访 11.6 年后，共确定了 768 例 IS 事件。与 SHBG 水平最高五分位数（参照）相比，SHBG 最低五分位数的女性在所有 3 个多变量模型中都有更高的 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]；趋势检验在所有模型中均<0.05）。在模型中纳入潜在的中介因素，如糖尿病、雌二醇和睾酮，可减弱但不能消除 SHBG 与 IS 之间的显著负相关。
结论-在这项前瞻性绝经后女性队列研究中，血清 SHBG 水平与 IS 风险之间存在统计学显著的负相关，这支持了 SHBG 可作为预测女性 IS 风险的分层工具的观点。
