{
  "abstract": "Objectives Female sex and anticitrullinated protein antibodies (ACPA) are associated with higher disease activity in rheumatoid arthritis (RA). Since disease-related inflammation is linked to cardiovascular risk, we explored whether sex and ACPA influenced the association between disease activity at study entry and cardiovascular risk in established RA.Methods We evaluated 4008 patients with prevalent RA from an international observational cohort enrolled between 1985 and 2012. Outcomes included major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction and stroke) and ischaemic cardiovascular events (iCVE: MACE, angina, revascularisation, transient ischaemic attack and peripheral arterial disease). Follow-up accrued from enrolment until the first event or censoring. Multivariable Cox models stratified by centre risk evaluated disease activity, sex, ACPA and their interactions.Results We documented 193 MACE and 299 iCVE. Disease activity and sex were associated with MACE (all p≤0.017) and iCVE (p≤0.005) but ACPA was only associated with MACE (p=0.043). A three-way interaction on MACE (p=0.034) but not iCVE was noted. Among ACPA-negative patients, disease activity was associated with MACE in males (HR 1.57 (95% CI 1.14 to 2.16)) but not females (p-for-interaction=0.022). Among ACPA-positive patients, neither the disease activity x sex interaction (p=0.929), nor main effect of disease activity on MACE (p=0.124) was significant, but male sex was (HR 1.61 (95% CI 1.15 to 2.27)). Among females, neither disease activity x ACPA interaction (p=0.523) nor disease activity (p=0.319) was significant for MACE, but ACPA was (HR 1.57 (95% CI 1.02 to 2.42)).Conclusions The effect of disease activity at enrolment on cardiovascular risk in prevalent RA varies across patient groups with different sex and ACPA characteristics.",
  "authors": [
    {
      "affiliations": [
        "Harbor-UCLA Medical Center, Torrance, California, USA",
        "The Lundquist Institute for Biomedical Innovation, Torrance, California, USA"
      ],
      "name": "George A Karpouzas"
    },
    {
      "affiliations": [
        "Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico"
      ],
      "name": "Virginia Pascual-Ramos"
    },
    {
      "affiliations": [
        "University of Cantabria, Santander, Spain",
        "IIS-Fundación Jiménez Díaz, Madrid, Spain"
      ],
      "name": "Miguel A Gonzalez-Gay"
    },
    {
      "affiliations": [
        "Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India"
      ],
      "name": "Durga P Misra"
    },
    {
      "affiliations": [
        "Mayo Clinic, Rochester, Minnesota, USA"
      ],
      "name": "Elena Myasoedova"
    },
    {
      "affiliations": [
        "Umeå University, Umeå, Sweden"
      ],
      "name": "Solbritt Rantapää-Dahlqvist"
    },
    {
      "affiliations": [
        "Laiko 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 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": [
        "The Dudley Group NHS Foundation Trust, 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": "An inTernationAl Cardiovascular Consortium for Rheumatoid Arthritis (ATACC-RA)"
    }
  ],
  "title": "Sex and anticitrullinated protein antibodies modify the relationship between inflammation and cardiovascular risk in rheumatoid arthritis",
  "uid": "fb4fe6ce-faf1-5010-b812-026a25ac12cd"
}