Inflammation, arrhythmia burden and the thrombotic consequences of atrial fibrillation

Dwayne S.G. Conway and Gregory Y.H. Lip*

Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, UK

* Tel.: +44 121 507 5080; fax: +44 121 554 4083 (E-mail: g.y.h.lip{at}bham.ac.uk).

We read with great interest the article by Dernellis and Panaretou1 demonstrating that the use of methylprednisolone among patients with a single previous episode of persistent atrial fibrillation (AF) was associated with less recurrent AF episodes, which may possibly be explained by a reduction in circulating C-reactive protein (CRP) levels. The accompanying editorial2 provides a brief overview of the existing evidence for an association between CRP and AF, and concludes that there is "great clinical potential" for anti-inflammatory therapies in the prevention and treatment of AF. We concur with the latter, and wish to suggest that anti-inflammatory strategies may not only reduce the arrhythmia burden of AF but also favourably alter the prothrombotic or hypercoagulable state associated with AF, which leads to the high risk of stroke and thromboembolism in this condition.

Indeed, we reported high plasma levels of CRP and interleukin-6 (IL-6) among patients with AF, which were independently related to indices of the prothrombotic state in AF (e.g., CRP to fibrinogen, IL-6 to tissue factor) 3. In another study of patients with AF, we found a relationship between CRP and the presence of dense spontaneous echocontrast in the left atrium or the left atrial appendage on transoesophageal echocardiography 4, which is a well-recognised independent predictor for stroke and thromboembolism in AF. Whilst the prognostic significance of CRP and IL-6 in the prediction of vascular events is well established among general populations 5, we have also demonstrated that indices of the prothrombotic state and inflammatory markers (IL6, but not CRP) may predict stroke and vascular events in AF 6,7.

Clearly, the effect of anti-inflammatory strategies upon the prothrombotic state needs to be established. Dernellis and Panaretou1 state that, "The AF inflammatory hypothesis needs more study to be widely acceptable". Although further work is needed on dissecting the confounding effect of vascular disease (itself associated with abnormal CRP and inflammatory markers), we broadly agree with their statement. However, we emphasise that the possibility that anti-inflammatory strategies might prevent both the arrhythmia burden and the thrombotic consequences of AF must not be overlooked.

References

  1. Dernellis J, Panaretou M. Relationship between C-reactive protein concentrations during glucocorticoid therapy and recurrent atrial fibrillation Eur. Heart J. 2004;25:1100-1107.[Abstract/Free Full Text]
  2. Abdelhadi RH, Chung MK, Van Wagoner DR. New hope for the prevention of recurrent atrial fibrillation Eur. Heart J. 2004;25:1089-1090.[Free Full Text]
  3. Conway DS, Buggins P, Hughes E, et al. Relationship of interleukin-6 and C-reactive protein to the prothrombotic state in chronic atrial fibrillation J. Am. Coll. Cardiol. 2004;43:2075-2082.[CrossRef][Medline]
  4. Conway DS, Buggins P, Hughes E, et al. Relation of interleukin-6, C-reactive protein, and the prothrombotic state to transesophageal echocardiographic findings in atrial fibrillation Am. J. Cardiol. 2004;93:1368-1373.[CrossRef][Medline]
  5. Ridker PM. Role of inflammatory biomarkers in prediction of coronary heart disease Lancet 2001;358:946-947.[CrossRef][Medline]
  6. Conway DSG, Pearce LA, Chin BS, et al. Prognostic value of plasma von willebrand factor and soluble P-selectin as indices of endothelial damage and platelet activation in 994 patients with nonvalvular atrial fibrillation Circulation 2003;107:3141-3145.[Abstract/Free Full Text]
  7. Conway DS, Buggins P, Hughes E, et al. Prognostic significance of raised plasma levels of interleukin-6 and C-reactive protein in atrial fibrillation. Am Heart J 2004; in press (September issue).




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