Background/Purpose: Rheumatoid arthritits (RA) patients have an increased risk of mortality from cardiovascular (CV) disease.  Proposed adaptation of CV risk score models in RA patients include criteria such as anti-cyclic citrullinated peptide antibodies (ACPA) positivity.  The existing literature on the association between ACPA positivity and CV risk is not definitive.^1-3    

Methods: This is a retrospective chart review of patients over 18 years of age with ACPA testing between 2007 and 2013 at a single academic center.  Patients with non-RA autoimmune disease were excluded.  Information about RA diagnosis and treatment, CV risk factors and CV events was collected.  Statistical methods included chi-square tests, t-tests, Wilcoxon Rank Sum tests, Fisher’s exact tests, simple logistic regression and multivariable logistic regression.  

Results: 2,030 records were reviewed.  309 patients with non-RA autoimmune disease were excluded.  The mean RA duration was 12.1 years.  RA and non-RA groups were similar in gender, tobacco status, hyperlipidemia, statin use, chronic kidney disease, and diabetes; significant differences included race, BMI, and systolic blood pressure.  Primary outcomes included coronary artery disease (CAD, defined as acute coronary syndrome or intervention), stroke (CVA, defined as clinical or radiographic stroke or transient ischemic attack), and a combined outcome (CAD or CVA).   The combined outcome occurred in 173 patients.  There was a significant association between an increasing prevalence of the combined outcome and ACPA quartile in all patients (p=0.002) and in RA patients (p=0.05).  A similar trend was seen in non-RA patients but did not reach statistical significance. There was an increased odds ratio of the combined outcome with each increasing ACPA quartile in all patients (p=0.002) (Figure 1).  Subgroup analyses of the RA and non-RA groups did not reach statistical significance, though the trend was preserved.      

Conclusion: Increased ACPA is associated with increased risk of the combined outcome of CVA or CAD.  To the authors’ knowledge, this is the first study to demonstrate progressively increased risk of CV disease with extent of ACPA elevation.  Although statistical significance was not reached in non-RA patients, the observed trends warrant larger studies to evaluate this population.   References:

1. López-Longo FJ, et al. Association between anti-cyclic citrullinated peptide antibodies and ischemic heart disease in patients with rheumatoid arthritis. Arthritis Rheum 2009;61(4):419-24.

2. Cambridge G, et al. Antibodies to citrullinated peptides and risk of coronary heart disease. Atherosclerosis 2013;228(1):243-6.

3. Mackey RH, et al. Rheumatoid arthritis, anti-cyclic citrullinated peptide positivity, and cardiovascular disease risk in the women’s health initiative. Arthritis Rheum 2015;67(9):2311-22.