From the Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neuroscience, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (S.G., H.C.S., A.I.B., D.L.P., Z.M., .M.R.); and Department of Neurology, Medical University of Vienna, Vienna, Austria (S.G.).
Stroke. 2015 Nov;46(11):3117-23. doi: 10.1161/STROKEAHA.115.011021. Epub 2015 Oct 8.
Copeptin, the c-terminal portion of provasopressin, is a useful prognostic marker in patients after myocardial infarction and heart failure. More recently, high levels of copeptin have also been associated with worse functional outcome and increased mortality within the first year after ischemic stroke and transient ischemic attack (TIA). However, to date, there are no published data on whether copeptin predicts long-term risk of vascular events after TIA and stroke.
We measured copeptin levels in consecutive patients with TIA or ischemic stroke in a population-based study (Oxford Vascular Study) recruited from 2002 to 2007 and followed up to 2014. Associations with risk of recurrent vascular events were determined by Cox-regression.
During ≈6000 patient-years in 1076 patients, there were 357 recurrent vascular events, including 174 ischemic strokes. After adjustment for age, sex, and risk factors, copeptin was predictive of recurrent vascular events (adjusted hazard ratio per SD, 1.47; 95% confidence interval, 1.31-1.64; P=0.0001), vascular death (1.85; 1.60-2.14; P<0.0001), all-cause death (1.75; 1.58-1.93; P<0.0001), and recurrent ischemic stroke (1.22; 1.04-1.44; P=0.017); and improved model-discrimination significantly: net reclassification improvement for recurrent vascular events (32%; P<0.0001), vascular death (55%; P<0.0001), death (66%; P<0.0001), and recurrent stroke (16%; P=0.044). The predictive value of copeptin was largest in patients with cardioembolic index events (adjusted hazard ratio, 1.84; 95% confidence interval, 1.53-2.20 versus 1.31, 1.14-1.50 in noncardioembolic stroke; P=0.0025). In patients with cardioembolic stroke, high copeptin levels were associated with a 4-fold increased risk of vascular events within the first year of follow-up (adjusted hazard ratio, 4.02; 95% confidence interval, 2.13-7.70).
In patients with TIA and ischemic stroke, copeptin predicted recurrent vascular events and death, particularly after cardioembolic TIA/stroke. Further validation is required, in particular, in studies using more extensive cardiac evaluation.
加压素原 C 端片段 copeptin 是心肌梗死和心力衰竭患者预后的有用标志物。最近，copeptin 水平升高也与缺血性卒中和短暂性脑缺血发作（TIA）后 1 年内功能结局较差和死亡率增加相关。然而，迄今为止，尚无关于 copeptin 是否预测 TIA 和卒中长期血管事件风险的发表数据。
我们在 2002 年至 2007 年期间从一项基于人群的研究（牛津血管研究）中连续测量了 TIA 或缺血性卒中患者的 copeptin 水平，并随访至 2014 年。采用 Cox 回归确定与复发性血管事件风险的相关性。
在 1076 例患者约 6000 患者年中，发生了 357 例复发性血管事件，包括 174 例缺血性卒中。经年龄、性别和危险因素校正后，copeptin 可预测复发性血管事件（每标准差校正风险比，1.47；95%置信区间，1.31-1.64；P=0.0001）、血管性死亡（1.85；1.60-2.14；P<0.0001）、全因死亡（1.75；1.58-1.93；P<0.0001）和复发性缺血性卒中（1.22；1.04-1.44；P=0.017）；且显著改善模型区分度：复发性血管事件（32%；P<0.0001）、血管性死亡（55%；P<0.0001）、死亡（66%；P<0.0001）和复发性卒中（16%；P=0.044）的重新分类改善有统计学意义。在心源性栓塞指数事件患者中，copeptin 的预测价值最大（校正风险比，1.84；95%置信区间，1.53-2.20 与非心源性卒中的 1.31、1.14-1.50；P=0.0025）。在心源性栓塞性卒中患者中，高 copeptin 水平与随访 1 年内血管事件风险增加 4 倍相关（校正风险比，4.02；95%置信区间，2.13-7.70）。
在 TIA 和缺血性卒中患者中，copeptin 可预测复发性血管事件和死亡，尤其是在心源性 TIA/卒中后。需要进一步验证，特别是在使用更广泛的心脏评估的研究中。
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