{
  "abstract": "Objectives Rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) are linked to disease activity, severity and cardiovascular risk in rheumatoid arthritis (RA). Since RA-related inflammation associates with cardiovascular disease, we investigated whether RF and ACPA status influence the relationship between RA activity and event risk.Methods We assessed 3952 cardiovascular disease-free patients with prevalent RA registered in an international observational consortium between 1985 and 2012. Main outcome was a first major adverse cardiovascular event (MACE) including myocardial infarction, stroke and cardiovascular death. Follow-up accrued from enrolment until first MACE or censoring. Multivariable Cox models stratified by centre risk evaluated disease activity, RF, ACPA and their interactions.Results We recorded 184 first MACE events over 22 981 patient-years. Disease activity associated with MACE (HR 1.18 (95% CI 1.03 to 1.35)), whereas RF (HR 1.26 (0.82 to 1.94)) and ACPA (HR 1.25 (0.85 to 1.83)) did not reach statistical significance, though CIs were wide and a clinically meaningful association cannot be excluded. A three-way interaction between disease activity, RF and ACPA on MACE (p for interaction=0.044) was observed. RA activity associated with MACE in seronegative and double seropositive (p≤0.047), but not single RF-positive or ACPA-positive patients. Among RF-negative participants, RA activity was linked to MACE in ACPA-negative but not positive ones (p for interaction=0.003). Among ACPA-positive patients, disease activity was linked to MACE in RF-positive but not RF-negative ones (p for interaction=0.040).Conclusions Disease activity may better discriminate inflammation-driven cardiovascular risk in seronegative and double seropositive than single RF-positive or ACPA-positive patients. Risk protection through lowering disease activity may be serostatus dependent.",
  "authors": [
    {
      "affiliations": [
        "Harbor-UCLA Medical Center, Torrance, California, USA",
        "The Lundquist Institute for Biomedical Innovation, Torrance, California, USA"
      ],
      "name": "George A Karpouzas"
    },
    {
      "affiliations": [
        "University of Cantabria, Santander, Spain",
        "IIS-Fundación Jiménez Díaz, Madrid, Spain"
      ],
      "name": "Miguel A Gonzalez-Gay"
    },
    {
      "affiliations": [
        "Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico"
      ],
      "name": "Virginia Pascual-Ramos"
    },
    {
      "affiliations": [
        "Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India"
      ],
      "name": "Durga Prasanna Misra"
    },
    {
      "affiliations": [
        "Mayo Clinic, Rochester, Minnesota, USA"
      ],
      "name": "Elena Myasoedova"
    },
    {
      "affiliations": [
        "Umeå University, Umeå, Sweden"
      ],
      "name": "Solbritt Rantapää-Dahlqvist"
    },
    {
      "affiliations": [
        "Laikon Hospital, Athens, Greece"
      ],
      "name": "Petros Sfikakis"
    },
    {
      "affiliations": [
        "University of Witwatersrand, Johannesburg, South Africa"
      ],
      "name": "Patrick Dessein"
    },
    {
      "affiliations": [
        "University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Carol A Hitchon"
    },
    {
      "affiliations": [
        "Hospital Universitario Dr. José E. González, Monterrey, Mexico"
      ],
      "name": "Dionicio Galarza-Delgado"
    },
    {
      "affiliations": [
        "Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands"
      ],
      "name": "Piet Van Riel"
    },
    {
      "affiliations": [
        "Diakonhjemmet Hospital, Oslo, Norway"
      ],
      "name": "Anne-Grete Semb"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark",
        "Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"
      ],
      "name": "Ellen M Hauge"
    },
    {
      "affiliations": [
        "Department of Rheumatology, Hygeia Hospital, Athens, Greece and University of Birmingham, Birmingham, UK"
      ],
      "name": "George D Kitas"
    },
    {
      "affiliations": [
        "Harbor-UCLA Medical Center, Torrance, California, USA",
        "The Lundquist Institute for Biomedical Innovation, Torrance, California, USA"
      ],
      "name": "Sarah R Ormseth"
    },
    {
      "affiliations": [],
      "name": "for An inTernationAl Cardiovascular Consortium for Rheumatoid Arthritis (ATACC-RA)"
    }
  ],
  "title": "Rheumatoid factor and anticitrullinated protein antibody status jointly influence the association between disease activity and cardiovascular risk in rheumatoid arthritis",
  "uid": "0e9f926f-8ebc-5e66-829b-5d1ff5805669"
}