CLINICAL RESEARCH: ELECTROPHYSIOLOGY
Relationship of interleukin-6 and C-Reactive protein to the prothrombotic state in chronic atrial fibrillation
Dwayne S. G. Conway, MRCP*,
Peter Buggins, BSc*,
Elizabeth Hughes, MD* and
Gregory Y. H. Lip, MD, FACC*,*
* Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, England, UK
Manuscript received November 4, 2003;
accepted November 25, 2003.
* Reprint requests and correspondence: Prof. Gregory Y. H. Lip, Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, England, UK.
g.y.h.lip{at}bham.ac.uk
OBJECTIVES: We sought to test the hypothesis that there is a relationship between inflammation and the prothrombotic state in atrial fibrillation (AF).
BACKGROUND: Atrial fibrillation is associated with a prothrombotic or hypercoagulable state, which may contribute to an increased risk of stroke and thromboembolism. Inflammation may be involved in the pathogenesis of AF, but the role of inflammation in the pathophysiology of the prothrombotic state of AF has not been studied in detail, despite evidence of a link between inflammation and arterial atherothrombotic disorders.
METHODS: We measured plasma indexes of inflammation (C-reactive protein [CRP] and interleukin-6 [IL-6]) and the prothrombotic state, including markers of platelet activation (soluble P-selectin), endothelial damage/dysfunction (von Willebrand factor), the coagulation cascade (tissue factor [TF], fibrinogen), and indexes of blood rheology (plasma viscosity, plasma fibrinogen, and hematocrit) in 106 patients with chronic AF and 41 healthy control subjects included in a cross-sectional analysis.
RESULTS: Compared with controls, AF patients had higher levels of IL-6 (p = 0.034), CRP (p = 0.003), TF (p = 0.019), and plasma viscosity (p = 0.045). Plasma IL-6 levels were higher among AF patients at "high" risk of stroke (p = 0.003). After adjusting for potential confounding clinical variables (e.g., vascular disease), AF remained significantly associated with a raised logarithmic transformation (log) of TF (p = 0.04), but the relationships between AF and log IL-6, log CRP, and plasma viscosity became nonsignificant. Among AF patients, log TF (p < 0.001) and high stroke risk (p = 0.003) were independent associates of log IL-6 (adjusted r2 = 0.443), whereas log fibrinogen (p < 0.001) and plasma viscosity (p = 0.04) were independent associates of log CRP (adjusted r2 = 0.259).
CONCLUSIONS: Increased plasma IL-6, CRP, and plasma viscosity support the case for the existence of an inflammatory state among "typical" populations with chronic AF. These indexes of inflammation are related to indexes of the prothrombotic state and may be related to the clinical variables of the patients (underlying vascular disease and co-morbidities), rather than simply to the presence of AF itself.
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Abbreviations and Acronyms
| | AF | = atrial fibrillation | | CRP | = C-reactive protein | | IL-6 | = interleukin-6 | | sP-sel | = soluble P-selectin | | TF | = tissue factor | | vWF | = von Willebrand factor |
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