Background/Purpose

Rheumatoid arthritis (RA) has been shown to be a risk factor for cardiovascular disease (CVD). Both elevated rheumatoid factor (RF) and anti-citrullinated protein antibodies have been reported to be associated with substantially higher risk of CVD and mortality among RA patients. However, the correlation between RF and CVD in the general population remains unclear. This study examines whether RF is associated with CVD in apparently healthy individuals.

Methods

All participants presenting to the Center for Preventive Medicine at St. Luke’s International Hospital in Tokyo, Japan from April 2004 to March 2013 for an annual health screening were included in this retrospective, cross-sectional study. The goals of this employer-mandated screening program are early detection of chronic disease and identification of risk factors. In addition to various CVD risk factors, RF is also routinely measured for early detection of rheumatoid arthritis.

Participants were divided into two groups by the presence of self-reported CVD. Using this as the primary outcome, we compared several parameters including RF positivity (>15 IU/ml), age, male gender, height, weight, body-mass index (BMI), waist circumference (WC), body fat percentage, systolic blood pressure (SBP), diastolic blood pressure (DBP), lipid profile, HbA1c, fasting blood glucose (FBG), uric acid (UA), C-reactive protein (CRP), percentage of ever-smokers and ever-drinkers, presence of self-reported CVD risk factors including dyslipidemia (DL), diabetes mellitus (DM) and hypertension (HTN), and family history of CVD. We evaluated whether whether RF positivity was independently associated with CVD using multivariate regression analysis.

Results

Of 111,021 individuals presenting for health checkup during the study period, 110,856 (99.9%) provided complete datasets regarding our parameters of interests. Of these, mean age was 46.0±12.0 (48.9% men) and 1,863 (1.7%) reported a history of CVD.

On univariate analysis, individuals with CVD were more likely to be male (70 vs. 48.5%), older (62.7 vs. 45.8 years), and have RF positivity (12.4 vs. 8.9%). Those with CVD also had poorer metabolic markers including BMI (23.7 vs. 22.3), WC (85.3 vs. 79.9cm), SBP (128 vs. 117mmHg), DBP (77.9 vs. 72.3mmHg), cholesterol ratio (3.7 vs. 3.4), HbA1c (5.9 vs. 5.5%), FBG (108 vs. 99mg/dl), CRP (0.19 vs. 0.12mg/dl). Health history was also suboptimal in the CVD group, including ever-smoking (57.8 vs. 40.0%); history of CVD risk factors such as DL, DM and HTN (22.3 vs. 4.4%, 2.4 vs. 0.3% and 35.9 vs. 7.1%, respectively); and family CVD history (37.1 vs. 22.2%). p-value < 0.001 for all.

On multivariate analysis, however, RF positivity was not correlated with CVD (1.06, 95%CI 0.91-1.22), in either men (1.03, 95%CI 0.85-1.23) or women (1.10, 95%CI 0.86-1.42) after adjustment for clinically established risk factors.

Conclusion

Despite its association with CVD in individuals with RA, RF does not appear to be correlated with CVD and appears to be inappropriate for use as a CVD screening test in apparently healthy individuals. Further investigations to clarify the reason for this discrepancy between RA patients and general population are warranted in the future.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-association-between-rheumatoid-factor-and-cardiovascular-disease-in-healthy-adults/