Center for Stroke Research Berlin, Charité Universitätsmedizin Berlin, Germany.
J Am Coll Cardiol. 2012 Jul 24;60(4):346-54. doi: 10.1016/j.jacc.2012.04.024.
The purpose of this study was to investigate neuropeptides in patients presenting with symptoms of acute cerebrovascular disease.
The precursor neuropeptides proenkephalin A (PENK-A) and protachykinin (PTA) are markers of blood-brain barrier integrity and have been recently discussed in vascular dementia and neuroinflammatory disorders.
In a prospective observational study, we measured plasma PENK-A and PTA concentrations in 189 consecutive patients who were admitted with symptoms of acute stroke. Plasma concentrations were determined by sandwich immunoassay; lower detection limits were 15.6 pmol/l (PENK-A) and 22 pmol/l (PTA). Clinical outcome was assessed at 3 months for mortality, major adverse cerebro/cardiovascular events, and functional outcome (modified Rankin scale).
PENK-A was significantly elevated in patients with ischemic stroke (n = 124; 65.6%) compared to patients with transient ischemic attack (n = 16; 8.5%) and to patients with nonischemic events (n = 49; 25.9%): median (interquartile range), stroke 123.8 pmol/l (93 to 160.5); transient ischemic attack 114.5 pmol/l (85.3 to 138.8); and nonischemic event 102.8 pmol/l (76.4 to 137.6; both groups vs. stroke p < 0.05). High concentrations of PENK-A, but not PTA, were related to severity of stroke as assessed by National Institutes of Health Stroke Scale (NIHSS [r = 0.225; p = 0.002]) and to advanced functional disability (modified Rankin Scale score 3 to 6 vs. 0 to 2: 135.1 pmol/l [99.2 to 174.1] vs. 108.9 pmol/l [88.6 to 139.5]; p = 0.014). After adjusting for age, NIHSS, and brain lesion size (computed tomography), PENK-A predicted mortality (hazard ratio [HR] for log-10 PENK-A in pmol/l: 4.52; 95% confidence interval [CI]: 1.1 to 19.0; p < 0.05) and major adverse cerebro/cardiovascular events (HR: 6.65; 95% CI: 1.8 to 24.9; p < 0.05). Patients in the highest quartile of PENK-A (cutoff >153 pmol/l) had an increased risk of mortality (HR: 2.40; 95% CI: 1.02 to 5.40; p < 0.05) and of major adverse cerebro/cardiovascular events (HR: 2.23; 95% CI: 1.10 to 4.54; p < 0.05).
PENK-A is a prognostic biomarker in the acute phase of ischemic stroke. Elevated PENK-A concentrations are associated with ischemic stroke, severity of cerebral injury, and may have prognostic value for fatal and nonfatal events.
本研究旨在探讨急性脑血管病患者的神经肽。
前脑啡肽原 A（PENK-A）和原促甲状腺素（PTA）等前体神经肽是血脑屏障完整性的标志物，最近在血管性痴呆和神经炎症性疾病中进行了讨论。
在一项前瞻性观察性研究中，我们测量了 189 例连续入院的急性中风患者的血浆 PENK-A 和 PTA 浓度。采用夹心免疫分析法测定血浆浓度；检测下限分别为 15.6 pmol/L（PENK-A）和 22 pmol/L（PTA）。在 3 个月时评估临床结局，包括死亡率、主要不良脑/心血管事件和功能结局（改良 Rankin 量表）。
与短暂性脑缺血发作（n = 16；8.5%）和非缺血性事件（n = 49；25.9%）相比，缺血性中风患者（n = 124；65.6%）的 PENK-A 明显升高：中位数（四分位数范围），中风 123.8 pmol/L（93 至 160.5）；短暂性脑缺血发作 114.5 pmol/L（85.3 至 138.8）；非缺血性事件 102.8 pmol/L（76.4 至 137.6；两组与中风相比 p < 0.05）。高浓度的 PENK-A，但不是 PTA，与 NIHSS 评估的中风严重程度（NIHSS [r = 0.225；p = 0.002]）和高级功能残疾（改良 Rankin 量表评分 3 至 6 与 0 至 2：135.1 pmol/L [99.2 至 174.1] 与 108.9 pmol/L [88.6 至 139.5]；p = 0.014）相关。在校正年龄、NIHSS 和脑损伤大小（计算机断层扫描）后，PENK-A 预测死亡率（log10 PENK-A 每 pmol/L 的风险比 [HR]：4.52；95%置信区间 [CI]：1.1 至 19.0；p < 0.05）和主要不良脑/心血管事件（HR：6.65；95% CI：1.8 至 24.9；p < 0.05）。PENK-A 最高四分位数（截断值 >153 pmol/L）的患者死亡率（HR：2.40；95% CI：1.02 至 5.40；p < 0.05）和主要不良脑/心血管事件（HR：2.23；95% CI：1.10 至 4.54；p < 0.05）风险增加。
PENK-A 是缺血性中风急性期的预后生物标志物。升高的 PENK-A 浓度与缺血性中风、脑损伤严重程度相关，可能对致命和非致命事件具有预后价值。
