Interleukin-6, tissue factor and von Willebrand factor in acute decompensated heart failure: relationship to treatment and prognosis

Arterial thrombotic and thromboembolic complications are increased in congestive heart failure (CHF), and are a particular problem in acute decompensated heart failure, which carries a poor prognosis. As interleukin-6 (IL-6) has been shown to induce the potent procoagulant tissue factor (TF) in experimental models, we hypothesized that the pro-inflammatory IL-6 may be one mechanism contributing to thrombosis in heart failure, mediated via endothelial expression of TF on activated/damaged cells [indicated by plasma von Willebrand factor (vWF)]. Seventy-seven patients (67% men, New York Heart Association class III-IV, 87%) with acute CH F were recruited, and were compared with 53 chronic stable CHF patients in sinus rhythm (66% men, New York Heart Association class III-IV, 2%) and 37 healthy controls (68% men). Acute CHIF patients in sinus rhythm had elevated baseline levels of IL-6 (P< 0.0001), TF (P= 0.041) and vWF (P < 0.0001) (all measured by enzyme-linked immunosorbent assay) compared with both chronic CHIF and healthy control groups. A correlation exists in acute CHF between baseline TF and IL-6 (Spearman r= 0.64, P < 0.0001). After 3 months treatment, with control or alleviation of heart failure symptoms in 40 patients, there was a fall in levels of IL-6 (P < 0.0001) and vWF (P < 0.0001), but levels still remained significantly higher than healthy controls. Patients who died at 6 months follow-up also had higher baseline levels of IL-6 (P = 0.008), TF (P = 0.037) and vWF (P = 0.039) when compared with those who remained alive. Elevated IL-6 may contribute to the thrombotic and thromboembolic complications in acute heart failure, in a process mediated via increased TF and vWF. Improvement of symptoms and plasma markers after treatment of acute CHF and prediction of prognosis by the markers may be useful in the clinical setting. (C) 2003 Lippincott Williams Wilkins.