Chin B S P, Blann A D, Gibbs C R, Chung N A Y, Conway D G, Lip G Y H
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.
Eur J Clin Invest. 2003 Nov;33(11):941-8. doi: 10.1046/j.1365-2362.2003.01252.x.
Congestive heart failure (CHF) carries a poor prognosis with a high mortality rate, frequent hospitalizations and increased risk of thrombotic complications such as stroke. Cytokines may contribute to the progression and prothrombotic state of CHF, including the pro-inflammatory interleukin-6 (IL-6) and the pro-angiogenic vascular endothelial growth factor (VEGF), both of which are raised in CHF. The procoagulant properties of both cytokines may be mediated via tissue factor (TF), a potent clotting activator. We hypothesized that plasma levels of these markers, as well as levels of plasma viscosity, fibrinogen, soluble P-selectin and von Willebrand factor (markers of abnormal rheology, clotting, platelet activation, and endothelial damage, respectively) will be useful in predicting morbidity and mortality in chronic stable CHF.
One hundred and twenty consecutive out-patients with chronic stable CHF (92 males; mean [SD] age 64 [11] years, mean [SD] left ventricular ejection fraction of 29 [6]%) were recruited and followed for 2 years during which 42 patients reached a clinical end-point of all-cause mortality and cardiovascular hospitalizations, including stroke and myocardial infarction. Plasma IL-6 (P=0.003) and TF (P=0.013) levels, but not other research indices, were higher in those who suffered events compared with those without events. Predictors of end-points were high (> or =median) TF (P=0.011), and IL-6 (P=0.023) levels, as well as the lowest quartile of a left ventricular ejection fraction (P=0.007). A strong correlation was present between TF and IL-6 levels (r=0.59; P<0.0001) and with VEGF levels (r=0.43; P<0.0001).
IL-6 and TF are predictors of poor prognosis in chronic CHF, raising the hypothesis that IL-6 may contribute to the progression and thrombotic complications of CHF via its actions on TF expression. Although VEGF did not independently predict outcome in chronic CHF, the possibility arises that it may act with IL-6 to induce TF expression.
充血性心力衰竭（CHF）预后较差，死亡率高，常需住院治疗，且血栓形成并发症（如中风）的风险增加。细胞因子可能促使CHF进展并导致血栓前状态，其中包括促炎细胞因子白细胞介素-6（IL-6）和促血管生成的血管内皮生长因子（VEGF），二者在CHF患者体内水平均升高。这两种细胞因子的促凝特性可能通过组织因子（TF）介导，TF是一种强效凝血激活剂。我们推测，这些标志物的血浆水平以及血浆粘度、纤维蛋白原、可溶性P-选择素和血管性血友病因子（分别为异常流变学、凝血、血小板活化和内皮损伤的标志物）水平，将有助于预测慢性稳定型CHF的发病率和死亡率。
连续纳入120例慢性稳定型CHF门诊患者（男性92例；平均[标准差]年龄64[11]岁，平均[标准差]左心室射血分数为29[6]%），随访2年，期间42例患者达到全因死亡和心血管住院（包括中风和心肌梗死）的临床终点。与未发生事件的患者相比，发生事件的患者血浆IL-6（P=0.003）和TF（P=0.013）水平升高，但其他研究指标未升高。终点的预测因素为TF水平高（≥中位数）（P=0.011）、IL-6水平高（P=0.023）以及左心室射血分数处于最低四分位数（P=0.007）。TF与IL-6水平之间存在强相关性（r=0.59；P<0.0001），与VEGF水平也存在强相关性（r=0.43；P<0.0001）。
IL-6和TF是慢性CHF预后不良的预测指标，这支持了IL-6可能通过作用于TF表达而促使CHF进展和发生血栓形成并发症的假说。虽然VEGF不能独立预测慢性CHF的预后，但它可能与IL-6共同作用诱导TF表达。
