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Extended report
Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis
  1. Cynthia S Crowson1,2,
  2. Silvia Rollefstad3,
  3. Eirik Ikdahl3,
  4. George D Kitas4,
  5. Piet L C M van Riel5,
  6. Sherine E Gabriel2,6,
  7. Eric L Matteson2,
  8. Tore K Kvien3,
  9. Karen Douglas4,
  10. Aamer Sandoo4,7,
  11. Elke Arts5,
  12. Solveig Wållberg-Jonsson8,
  13. Lena Innala8,
  14. George Karpouzas9,
  15. Patrick H Dessein10,11,
  16. Linda Tsang11,
  17. Hani El-Gabalawy12,
  18. Carol Hitchon12,
  19. Virginia Pascual Ramos13,
  20. Irazú Contreras Yáñez13,
  21. Petros P Sfikakis14,
  22. Evangelia Zampeli14,
  23. Miguel A Gonzalez-Gay15,
  24. Alfonso Corrales15,
  25. Mart van de Laar16,
  26. Harald E Vonkeman16,
  27. Inger Meek16,
  28. Anne Grete Semb3
  29. on behalf of A Trans-Atlantic Cardiovascular Consortium for Rheumatoid Arthritis (ATACC-RA)
    1. 1Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
    2. 2Division of Rheumatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
    3. 3Preventive Cardio-Rheuma Clinic, Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
    4. 4Department of Rheumatology, Dudley Group NHS Foundation Trust, West Midlands, UK
    5. 5Department of Rheumatic Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    6. 6Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
    7. 7School of Sport, Health and Exercise Sciences, Bangor University, Bangor, Wales, UK
    8. 8Department of Public Health and Clinical Medicine/Rheumatology, University of Umeå, Umeå, Sweden
    9. 9Division of Rheumatology, Harbor UCLA Medical Center RHU, Torrance, California, USA
    10. 10Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
    11. 11Rheumatology Division, UniversitairZiekenhuis and Vrije Universiteit, Brussel, Belgium
    12. 12Institute of Musculoskeletal Health and Arthritis, University of Manitoba, Winnipeg, Manitoba, Canada
    13. 13Department of Immunology and Rheumatology., Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
    14. 14First Department of Propedeutic Medicine, University of Athens, Athens, Greece
    15. 15Division of Rheumatology, Hospital Universitario Marques de Valdecilla, Santander (Cantabria), Spain
    16. 16Departmentof Rheumatology and Clinical Immunology, Hospital Medisch Spectrum Twente, Enschede, The Netherlands
    1. Correspondence to and Cynthia S Crowson, Mayo Clinic, 200 First St SW, Rochester, MN 55906, USA; crowson{at}mayo.edu

    Abstract

    Objectives Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA.

    Methods In 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions.

    Results 5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics).

    Conclusions In a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.

    • Cardiovascular disease
    • rheumatoid arthritis
    • risk factor
    • population attributable risk

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    Footnotes

    • CSC and SR are shared first authors.

    • Handling editor Hans WJ Bijlsma

    • Contributors Conceived and designed the research: CSC, SR, EI, GDK, PLCMvR, SEG, AGS. Acquired the data: CSC, SR, EI, GDK, PLCMvR, SEG, ELM, TKK, KD, AS, EA, SW-J, LI, GK, PHD, LT, HE-G, CH, VPR, ICY, PPS, EZ, MAG-G, AC, MvdL, HEV, IM, AGS. Performed statistical analysis: CSC. Data interpretation: CSC, SR, EI, GDK, PLCMvR, SEG, ELM, TKK, KD, AS, EA, SW-J, LI, GK, PHD, LT, HE-G, CH, VPR, ICY, PPS, EZ, MAG-G, AC, MvdL, HEV, IM, AGS. Drafted the manuscript: CSC, SR, EI, AGS. Made critical revision of the manuscript for key intellectual content: CSC, SR, EI, GDK, PLCMvR, SEG, ELM, TKK, KD, AS, EA, SW-J, LI, GK, PHD, LT, HE-G, CH, VPR, ICY, PPS, EZ, MAG-G, AC, MvdL, HV, IM, AGS.

    • Funding This work was supported by a collaborative agreement for independent research from Eli Lilly, a grant from the National Institute of Arthritis and Musculoskeletal and Skin Disease of the National Institutes of Health (grant number R01 AR046849), and grants from the Norwegian South East Health Authority (grant numbers 2013064, 2013010). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

    • Competing interests CSC reports grants from National Institute of Arthritis and Musculoskeletal and Skin Disease of the National Institutes of Health during the conduct of the study. AGS has received speaker honoraria and/or consulting fee from Merck/Schering-Plough, Abbott, BMS, UCB, Pfizer/Wyeth, Eli Lilly and Hoffmann-La Roche. TKK reports grants and personal fees from AbbVie, BMS, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira/Pfizer, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Roche, Sandoz and UCB. SR, EI, GDK, PLCMvR, SEG, ELM, KD, AS, EA, SW-J, LI, GK, PHD, LT, HE-G, CH, VPR, ICY, PPS, EZ, MAG-G, AC, MvdL, HEV and IM: none declared.

    • Ethics approval Mayo Clinic Institutional Review Board and Institutional Review Boards at each participating centre.

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

    • Data sharing statement The ATACC-RA consortium legal contract does not allow full access of patient information to be provided to a third party without prior approval from the ATACC-RA steering committee. However, access to the complete de-identified data can be made available following approval. Requests for approval can be sent to the corresponding author (CSC at crowson@mayo.edu), who will forward them to the ATACC-RA Steering Committee for approval.

    • Collaborators Additional ATACC-RA consortium members: Iris Colunga, Dionicio Galarza and José Ramón Azpiri-López, Hospital Universitario ’Dr José E González', Monterrey, Mexico; Elaine Husni and Robert Overman, Cleveland Clinic, Cleveland, Ohio, USA; Jaap Fransen, Department of Rheumatic Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Solbritt Rantapää-Dahlqvist, University of Umeå, Umeå, Sweden; and Daniel Solomon and Katherine Liao, Harvard Medical School Brigham and Women’s Hospital, Boston, Massachusetts, USA.

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