Rheumatoid Factor Ups Risk of 10-Year Cardiovascular Morbidity

RA in hand
RA in hand
Rheumatoid factor positivity was associated with occurrence of CVD, independently from anti-CCP positivity.

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.

Related Articles

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

follow @RheumAdvisor


  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.