Department of Emergency Medicine and Center for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Shock. 2013 May;39(5):427-32. doi: 10.1097/SHK.0b013e3182903f0d.
The objective of this study was to investigate the association of endothelial-related markers with organ dysfunction and in-hospital mortality to validate our earlier findings in a multicenter study. We hypothesize that (i) endothelial biomarkers will be associated with organ dysfunction and mortality in sepsis and that (ii) soluble fms-like tyrosine kinase 1 (sFlt-1) holds promise as a novel prognostic marker in sepsis.
This was a prospective, multicenter, observational study of a convenience sample of emergency department (ED) patients with a suspected infection presenting to one of four urban, academic medical center EDs between January 2009 and January 2010. We collected plasma while the patients were in the ED and subsequently assayed endothelial-related biomarkers, namely, sFlt-1, soluble E-selectin, soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, and plasminogen activator inhibitor 1 (PAI-1). Outcomes were organ dysfunction and in-hospital mortality.
We enrolled a total of 166 patients: 63 with sepsis (38%), 61 with severe sepsis (37%), and 42 with septic shock (25%). All endothelial biomarkers were significantly associated with sepsis severity, P < 0.002. We found a significant intercorrelation between all biomarkers, strongest between sFlt-1 and PAI-1 (r = 0.61, P < 0.001) and PAI-1 and soluble E-selectin and soluble intercellular adhesion molecule 1 (r = 0.49, P < 0.001). Among the endothelial biomarkers, sFlt-1 had the strongest association with Sequential Organ Failure Assessment score (r = 0.58, P < 0.001). Soluble fms-like tyrosine kinase 1 and PAI-1 had the highest area under the operating receiver characteristic curve for mortality of 0.87.
This multicenter validation study confirms that markers of endothelial activation are associated with sepsis severity, organ dysfunction, and mortality in sepsis. This supports the hypothesis that the endothelium plays a central role in the pathophysiology of sepsis and may serve as a more accurate prediction tool and a target for therapies aimed at ameliorating endothelial cell dysfunction. In addition, sFLT-1 holds promise as a novel sepsis severity biomarker.
本研究旨在探讨内皮相关标志物与器官功能障碍和院内死亡率的关系，以验证我们在一项多中心研究中的早期发现。我们假设：（i）内皮生物标志物将与败血症中的器官功能障碍和死亡率相关；（ii）可溶性 fms 样酪氨酸激酶 1（sFlt-1）有望成为败血症中的一种新型预后标志物。
这是一项前瞻性、多中心、观察性研究，纳入了 2009 年 1 月至 2010 年 1 月期间在四家城市学术医疗中心急诊科就诊的疑似感染患者的便利样本。我们在患者就诊时采集血浆，并随后检测内皮相关生物标志物，即 sFlt-1、可溶性 E-选择素、可溶性细胞间黏附分子 1、可溶性血管细胞黏附分子 1 和纤溶酶原激活物抑制剂 1（PAI-1）。结局为器官功能障碍和院内死亡率。
我们共纳入 166 例患者：败血症 63 例（38%），严重败血症 61 例（37%），败血症性休克 42 例（25%）。所有内皮生物标志物与败血症严重程度均显著相关，P<0.002。我们发现所有生物标志物之间存在显著的相关性，sFlt-1 与 PAI-1 之间的相关性最强（r=0.61，P<0.001），PAI-1 与可溶性 E-选择素和可溶性细胞间黏附分子 1 之间的相关性最强（r=0.49，P<0.001）。在这些内皮生物标志物中，sFlt-1 与序贯器官衰竭评估评分的相关性最强（r=0.58，P<0.001）。sFlt-1 和 PAI-1 的死亡率受试者工作特征曲线下面积最高，为 0.87。
这项多中心验证研究证实，内皮激活标志物与败血症严重程度、器官功能障碍和死亡率相关。这支持了内皮在败血症病理生理学中起核心作用的假说，并可能作为更准确的预测工具和改善内皮细胞功能障碍的治疗靶点。此外，sFLT-1 有望成为一种新型败血症严重程度标志物。
