Association between anti-cyclic citrullinated peptide antibodies and ischemic heart disease in patients with rheumatoid arthritis

Arthritis Rheum. 2009 Apr 15;61(4):419-24. doi: 10.1002/art.24390.


Objective: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease that may not always be related to the presence of traditional cardiovascular risk factors. The aim of this study was to determine if anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with cardiovascular disease in patients with RA.

Methods: Anti-CCP antibodies were determined by enzyme-linked immunosorbent assay in the earliest serum sample available from 937 patients with a diagnosis of RA. We studied the relationship between anti-CCP antibodies with traditional cardiovascular risk factors and cardiovascular events.

Results: We found positive anti-CCP antibodies (>25 units/ml) in 672 patients (71.7%). There was no association between the anti-CCP antibodies and cardiovascular risk factors such as smoking, hypertension, dyslipidemia, being overweight, or diabetes mellitus. However, patients who had positive anti-CCP antibodies experienced more frequent ischemic heart disease (6.5% versus 2.6%; odds ratio [OR] 2.58, 95% confidence interval [95% CI] 1.17-5.65) and had higher mortality rates (11.2% versus 6.8%; OR 1.72, 95% CI 1.01-2.91). Similar results were obtained when we considered anti-CCP titers 20-fold higher (>500 units/ml). Multivariable analysis showed that ischemic heart disease is independently associated with positive anti-CCP antibodies (OR 2.8, 95% CI 1.19-6.56; P = 0.009).

Conclusion: Anti-CCP antibodies in patients with RA are independently associated with the development of ischemic heart disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Anti-Idiotypic / blood*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / complications*
  • Arthritis, Rheumatoid / immunology
  • Biomarkers / blood
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / epidemiology*
  • Myocardial Ischemia / immunology
  • Peptides, Cyclic / immunology*
  • Prospective Studies
  • Risk Factors


  • Antibodies, Anti-Idiotypic
  • Biomarkers
  • Peptides, Cyclic
  • cyclic citrullinated peptide