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Predicting atrial fibrillation recurrence with circulating inflammatory markers in patients in sinus rhythm at high risk for atrial fibrillation: data from the GISSI atrial fibrillation trial
  1. Serge Masson1,
  2. Aneta Aleksova2,
  3. Chiara Favero1,
  4. Lidia Staszewsky1,
  5. Marino Bernardinangeli3,
  6. Chiara Belvito4,
  7. Giovanni Cioffi5,
  8. Gianfranco Sinagra2,
  9. Carmine Mazzone6,
  10. Federico Bertocchi7,
  11. Tarcisio Vago8,
  12. Giuseppe Peri9,
  13. Ivan Cuccovillo9,
  14. Nobuhito Masuda10,
  15. Simona Barlera1,
  16. Alberto Mantovani9,11,
  17. Aldo P Maggioni12,
  18. Maria Grazia Franzosi1,
  19. Marcello Disertori13,
  20. Roberto Latini1
  21. on behalf of the GISSI-AF investigators
  1. 1Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche ‘Mario Negri’, Milan, Italy
  2. 2Cardiovascular Department, ‘Ospedali Riuniti’ and University of Trieste, Trieste, Italy
  3. 3Azienda USL 4 Terni, Terni, Italy
  4. 4Policlinico San Matteo, Pavia, Italy
  5. 5Casa di Cura Villa Bianca, Trento, Italy
  6. 6Azienda Servizi Sanitari Triestina, Trieste, Italy
  7. 7Novartis Italia SpA, Origgio, Italy
  8. 8Ospedale Luigi Sacco, Milan, Italy
  9. 9Istituto Clinico Humanitas, Rozzano, Italy
  10. 10Perseus Proteomics, Tokyo, Japan
  11. 11Department of Translational Medicine, Università degli Studi di Milano, Milan, Italy
  12. 12ANMCO Research Center, Florence, Italy
  13. 13First Division of Cardiology, Ospedale Santa Chiara, Trento, Italy
  1. Correspondence to Dr Roberto Latini, Department of Cardiovascular Research, Istituto ‘Mario Negri’, via Giuseppe La Masa 19, 20156 Milan, Italy; roberto.latini{at}


Background Inflammation may play a significant role in the pathogenesis of atrial fibrillation (AF).

Objectives To examine the roles of three systemic inflammatory markers in predicting recurrent AF.

Methods The association between the plasma concentrations of high-sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6) and pentraxin-3 (PTX3) with echocardiographic parameters and with the time to first recurrence of AF was tested in 382 patients with a history of AF but in sinus rhythm at randomisation, enrolled in the GISSI-AF biohumoral study.

Results Baseline PTX3 was related to left atrial, but not to left ventricular chamber volume. During one year of follow-up, 204 patients (53.1%) had a recurrent AF. There were no significant differences in baseline median [Q1–Q3] plasma concentrations of IL-6, hsCRP and PTX3 among patients with (2.11 [1.47–3.74] pg/ml, 3.30 [1.40–6.80] mg/l and 4.66 [3.27–6.97] ng/ml, respectively) or without recurrent AF (2.09 [1.37–2.90] pg/ml, p=0.182; 3.00 [1.10–6.20] mg/l, p=0.333; 5.09 [3.22–7.98] ng/ml, p=0.637). At 6 and 12 months follow-up, AF patients had significantly higher concentrations of IL-6 and PTX3 than those in sinus rhythm, and those with most recent episodes of AF had higher hsCRP. Baseline levels of IL-6, hsCRP or PTX3 were not significantly associated with a higher risk of recurrence of AF.

Conclusion In patients with a history of AF, but without significant left ventricular dysfunction or heart failure, inflammatory biomarkers may be raised but are, at best, weak predictors of the risk for first recurrence of AF.

  • Atrial fibrillation
  • inflammation
  • clinical trial
  • prognosis
  • pentraxins
  • risk stratification
  • cytokines

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  • A complete list of the investigators who participated in the study is presented in the appendix.

  • Funding The GISSI studies and this substudy are supported by the Associazione Nazionale Medici Cardiologi Ospedalieri and by the Istituto di Ricerche Farmacologiche ‘Mario Negri’. The study is partially funded by a grant from the European Union Seventh Framework Programme, TOLERAGE (HEALTH-F4-2008-202156).

  • Competing interests SM, LS, APM, MGF, MD and RL received institutional research support from Novartis Pharma. FB is an employee of Novartis Pharma Italy, the company that funded the GISSI-AF trial. NM is an employee of Perseus Proteomics, which holds patent rights to the pentraxin-3 marker. Reagents for measuring circulating PTX3 were provided by Perseus Proteomics.

  • Ethics approval This study was conducted with the approval of the local ethics committees from the 36 Italian clinical centres that participated to the biomarkers substudy of the GISSI-AF trial.

  • Provenance and peer review Not commissioned; externally peer reviewed.