EHJ：循环血管生成素增加心源性休克病人死亡风险

急性心肌梗死病人院内死亡的主要病因是心源性休克。血管完整性被破坏后能导致休克临床表现和严重后果。血管生成素1可以保护血管，避免炎症反应和通透性改变，而血管生成素2则破坏内皮屏障功能。血管生成素1或2之间的失衡以及与血流动力学恶化、病人预后的关系都不明确。因此，德国Andreas Link研究小组对此在心源性休克病人中进行了前瞻性评估。结果发现，循环血管生成素是血管完整性破坏、组织低灌注低氧血症等的标志物，与心源性休克的预后和严重性密切相关。

本研究通过酶联免疫法检测血浆血管生成素1或2水平，分组为心源性休克组（CS，n=96），无并发症的急性心肌梗死（AMI，n=20）和年龄匹配的健康人群组（HC，n=20）。CS组与HC组相比，其血管生成素2升高了3倍（p<0.001），并且在非幸存者也是高的，而在幸存者，水平降低（p<0.001）。与之相反， CS组的血管生成素1下降达35倍(P < 0.001)。血管生成素1呈正相关，而血管生成素2与心功能指数和混合静脉血氧饱和度呈负相关（p<0.001）。为评估与病人预后的相关性，检测了2个结果变量：28天的死亡率和生存时间（随访时间1年）。病人入院后，血管生成素2在2500pg/ml以内时，对于心源性休克病人28天死亡率来说，其敏感性为61%，特异性为80%（通过受试者手术特征分析得出，曲线下面积=0.71± 0.06, P < 0.001）。根据Cox比例风险分析，入院时血管生成素2如果大于2500pg/ml，则是心源性休克病人1年期死亡率的独立危险因素（风险比2.11；95%可信区间1.03-4.36; P = 0.042）。

研究结论如下：循环血管生成素与心源性休克病人的预后及严重性密切相关。血管生成素2是心源性休克病人28天和1年期死亡率的独立危险因子。需要大量研究来定义血管生成素2的截止值和预测值。血管生成素可能是心源性休克病人存活的预后标志物和新的治疗靶点。

Circulating angiopoietins and cardiovascular mortality in cardiogenic shock
Aims
Vascular integrity is disturbed in shock contributing to clinical appearance and serious outcomes. While angiopoietin (Ang)-1 protects from vascular inflammation and leakage, Ang-2 disrupts endothelial barrier function. The imbalance of Ang-1 and Ang-2, their association to haemodynamic deterioration, and their prognostic relevance are not known and, thus, were prospectively evaluated in patients with cardiogenic shock (CS) in this study.
Methods and results
Plasma Ang-1 and Ang-2 were determined by the enzyme immunoassay in patients with CS (n = 96), uncomplicated acute myocardial infarction (AMI, n = 20) and age-matched healthy controls (HC, n = 20). Angiopoietin-2 was three-fold elevated in CS compared with HC (P < 0.001), remained elevated in non-survivors, and decreased in survivors (P < 0.001). In contrast, Ang-1 decreased up to 35-fold in CS (P < 0.001). Angiopoietin-1 was correlated and Ang-2 was inversely related to a cardiac power index and mixed venous oxygen saturation, respectively (P < 0.001 for all). To assess the prognostic relevance, two outcome variables were considered: the 28-day mortality and the survival time (follow-up time 1 year). For Ang-2 at admission a cut-off point of 2500 pg/mL had a sensitivity of 61% and a specificity of 80% to determine 28-day mortality in CS (confirmed by receiver operating characteristic analysis, area under the curve = 0.71 ± 0.06, P < 0.001). Angiopoietin-2 levels >2500 pg/mL at admission were observed to be an independent predictor for 1-year mortality in CS confirmed by Cox proportional hazard analysis [hazard ratio (HR) 2.11; 95% confidence interval (CI) 1.03–4.36; P = 0.042].
Conclusion
Circulating Angs are closely related to outcome and severity in CS. Angiopoietin-2 emerged as an independent predictor of 28-day and 1-year mortality in CS. Larger studies are required to define the cut-off and predictive values for Ang-2. Angiopoietins may be prognostic biomarkers for survival in CS and might represent a novel therapeutic target.