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Updated: Jun 19, 2026

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Published on: August 17, 2022
Autoantibodies and the risk of cardiovascular events
Kimberly P Liang1, Hilal Maradit Kremers, Cynthia S Crowson
1Department of Medicine and Division of Rheumatology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Insights
Rheumatoid factor (RF) and antinuclear antibody (ANA) positivity predict cardiovascular events and mortality in individuals with or without rheumatic diseases, highlighting immune dysregulation
Area of Science:
- Immunology
- Cardiology
- Rheumatology
Background:
- Autoimmunity and inflammation are linked to increased cardiovascular (CV) risk in rheumatoid arthritis patients.
- This association may extend to individuals without diagnosed rheumatic diseases.
Purpose of the Study:
- To investigate the association between rheumatoid factor (RF), antinuclear antibody (ANA), and cyclic citrullinated peptide antibody (CCP) positivity and the risk of CV events and mortality.
- To determine if these associations differ in individuals with and without rheumatic diseases.
Main Methods:
- Population-based cohort study utilizing RF, ANA, and CCP test data from 1990-2005.
- Outcomes including CV events (MI, HF, PVD) and mortality were tracked until April 2007.
- Cox models were employed for statistical analysis, adjusting for relevant covariates.
Main Results:
- RF and ANA positivity were significant predictors of CV events (HR 1.24, 1.26) and mortality (HR 1.43, 1.18) after adjustment.
- CCP positivity showed a non-significant association with CV events (HR 3.1).
Conclusions:
- RF and ANA positivity are significant predictors of CV events and mortality, irrespective of rheumatic disease status.
- These findings support the role of immune dysregulation in the development of cardiovascular disease.
Objective:
Inflammation and autoimmunity are associated with increased cardiovascular (CV) risk in patients with rheumatoid arthritis. This association may also be present in those without rheumatic diseases. Our purpose was to determine whether rheumatoid factor (RF), antinuclear antibody (ANA), and cyclic citrullinated peptide antibody (CCP) positivity are associated with increased risk of CV events and overall mortality in those with and without rheumatic diseases.
Methods:
We performed a population-based cohort study of all subjects who had a RF and/or ANA test performed between January 1, 1990, and January 1, 2000, and/or CCP test performed between September 1, 2003, and January 1, 2005, with followup until April 1, 2007. Outcomes were ascertained using diagnostic indices from complete medical records, including CV events [myocardial infarction (MI), heart failure (HF), and peripheral vascular disease (PVD)] and mortality. Cox models were used to analyze the data.
Results:
There were 6783 subjects with RF, 7852 with ANA, and 299 with CCP testing. Of these, 10.4%, 23.9%, and 14.7% were positive for RF, ANA, and CCP, respectively. Adjusting for age, sex, calendar year, comorbidity, and rheumatic disease, RF and ANA positivity were significant predictors of CV events [hazard ratio (HR) 1.24 and 1.26] and death (HR 1.43 and 1.18). Adjusting for age, CCP positivity was associated with CV events, but this association was not statistically significant (HR 3.1; 95% CI 0.8, 12.3).
Conclusion:
RF and ANA positivity are significant predictors of CV events and mortality in both those with and those without rheumatic diseases. These results support the role of immune dysregulation in the etiology of CV disease.
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