Autoantibodies and the risk of cardiovascular events.
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).


CONCLUSIONS
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.
Liang
Kimberly P
KP
Department of Medicine and Division of Rheumatology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Kremers
Hilal Maradit
HM
Crowson
Cynthia S
CS
Snyder
Melissa R
MR
Therneau
Terry M
TM
Roger
Veronique L
VL
Gabriel
Sherine E
SE
D000328:Adult; D000974:Antibodies, Antinuclear / Q000009:adverse effects / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000009:adverse effects / Q000097:blood / Q000276:immunology; D002318:Cardiovascular Diseases / Q000097:blood / Q000276:immunology / Q000401:mortality; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000009:adverse effects / Q000097:blood / Q000276:immunology; D011237:Predictive Value of Tests; D012217:Rheumatoid Factor / Q000009:adverse effects / Q000097:blood / Q000276:immunology; D012307:Risk Factors
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor