Rheumatoid Factor Ups Risk of 10-Year Cardiovascular Morbidity

A study of a large inception cohort of patients with rheumatoid arthritis (RA) revealed that a positive test for rheumatoid factor (RF) antibodies at baseline significantly increased the risk of 10-year cardiovascular (CV) morbidity. No such association was seen in patients who tested positive for anticyclic citrullinated peptide antibodies (anti-CCP), according to results published ahead of print in The Journal of Rheumatology.¹

The research team, from Radboud University Medical Centre in Nijmegen, The Netherlands, used data from the Nijmegen early RA inception cohort, an ongoing long-term observational study of patients with newly-diagnosed RA begun in 1985. Patients in the Nijmegen cohort receive standardized follow-up until death or withdrawal from the study.²

Eligibility for the present study was based on the availability of anti-CCP status, no history of cardiovascular disease (CVD) at baseline, and a follow-up of at least 6 months; 929 patients (628 anti-CCP-positive and 697 RF-positive) met the inclusion criteria.

There were 162 CV events (101 ischemic heart disease, 45 nonhemorrhagic cerebrovascular accidents, and 16 peripheral artery disease) in the 929 patients during follow-up, with a median of 7.5 years from date of diagnosis to date of event. CV events took place in 112 patients in the anti-CCP-positive group and 50 in the anti-CCP-negative group.

Statistical analysis showed no effect of anti-CCP status on CV outcomes. After adjustment for RA and CVD confounders, the hazard ratios for anti-CCP and RF were 1.17 (95% CI .82-1.67) and 1.52 (95% CI 1.00-2.30), respectively. CVD risk was highest in RF-positive, anti-CCP-negative patients (adjusted HR 2.09; 95% CI 1.18-3.71).

The investigators noted that prior studies on the influence of RF and anti-CCP on CV outcomes in patients with RA have yielded mixed results. “Despite the lack of association with CVD (in the present study), it cannot be ruled out that anti-CCP antibodies are contributing to atherosclerosis-associated inflammation in patients with RA,” they wrote.

Summary & Clinical Applicability

“In a large group of patients with RA, we found that neither the presence of anti-CCP antibodies nor their titer at moment of diagnosis associates with 10-year CVD,” concluded the investigators. “On the other hand, RF positivity was associated with occurrence of CVD, independently from anti-CCP positivity. This suggests that anti-CCP should not be considered an extra CVD risk factor in RA, irrespective of age at onset of disease. The involvement of RF as a predictive factor for occurrence of CVD in RA is still quite unclear.”

Limitaions & Disclosures

The investigators noted 2 potential limitations to the study:

• A lack of knowledge about changes in variables during follow-up
• A lack of knowledge about post-baseline treatment regimens, which have the potential to impact CVD outcomes

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References

1. Berendsen MLT, van Maaren MC, Arts EEA, den Broeder AA, Popa CD, Fransen J. Anticylic citrullinated peptide antibodies and rheumatoid factor as risk factors for 10-year cardiovascular morbidity in patients with rheumatoid arthritis: a large inception cohort study [published online July 1, 2017]. J Rheumatol. doi:10.3899/jrheum.160670
2. Welsing PMJ, van Riel PLCM. The Nijmegen inception cohort of early rheumatoid arthritis. J Rheumatol Suppl. 2004;69:14-21.