Higher levels of markers for early atherosclerosis in anti-citrullinated protein antibodies positive individuals at risk for RA, a cross sectional study.

OBJECTIVE: To identify differences in levels of serum biomarkers associated with atherosclerosis between anti-citrullinated protein antibodies (ACPA) positive groups. METHODS: Cross-sectional data were used from the Dutch Lifelines Cohort Study combined with data derived from RA risk and early RA studies conducted at the University Medical Center Groningen (UMCG). Serum biomarkers of inflammation, endothelial cell activation, tissue remodeling and adipokine, which were previously associated with atherosclerosis, were measured with Luminex in four ACPA positive groups with different characteristics: without joint complaints, with joint complaints, RA risk and early RA groups. RESULTS: Levels of C-reactive protein (CRP), Interleukin-6 (IL-6), Tumor Necrosis Factor Receptor 1 (TNFR1) and vascular endothelial growth factor (VEGF) were significantly higher in the RA risk and early RA groups compared to the joint complaints and the no joint complaints groups. The difference remained statistically significant after correcting for renal function, smoking and hypertension in multivariate logistic regression analysis, with focus on ACPA positive with joint complaints group versus RA risk group: CRP OR = 2.67, p = 0.033; IL-6 OR = 3.73, p = 0.019; TNFR1 OR = 1.003, p < 0.001; VGEF OR = 8.59, p = 0.019. CONCLUSION: Individuals at risk for RA have higher levels of inflammatory markers and VEGF, which suggests that they might also have a risk of higher cardiovascular disease (CVD); however, this does not apply to individuals with ACPA positivity with self-reported joint complaints or without joint complaints only. Therefore, it is important that individuals with RA risk are referred to a rheumatologist to rule in or out arthritis/development of RA and discuss CVD risk.

Higher skin autofluorescence in individuals at risk for rheumatoid arthritis: results from a large population-based cohort.

OBJECTIVES: To investigate skin autofluorescence (SAF) levels, an early indicator for cardiovascular disease, in relation to the presence of anticitrullinated protein antibodies (ACPA), joint complaints and rheumatoid arthritis (RA) in a large population-based cohort. METHODS: Cross-sectional data were used from 17346 participants of the Dutch Lifelines Cohort Study, of whom baseline SAF and ACPA levels were available. Individuals were divided into four groups: ACPA-negative controls (n=17211), ACPA-positive without joint complaints (n=49), ACPA-positive RA risk (n=31) and defined RA (n=52). Multinomial regression was used to compare SAF levels and correct for potential confounders. RESULTS: SAF levels were higher in the ACPA-positive RA risk group (OR 2.04, p=0.034) and the defined RA group (OR 3.10, p<0.001) compared to controls, but not in the ACPA-positive without joint complaints group (OR 1.07, p=0.875). The difference in SAF levels remained statistically significant in the defined RA group after adjusting for age (OR 2.09, p=0.011), smoking status, renal function or HbA1c. In the ACPA-positive RA risk group, the effect was found to be comparable (corrected for age: OR 2.09). CONCLUSIONS: Our results indicate that ACPA-positive individuals with RA risk have elevated SAF levels, which is regarded as a non-invasive marker for oxidative stress and a possible indicator for development of cardiovascular disease. Therefore, it is important to conduct further studies to explore if, in ACPA-positive individuals with RA risk and no diagnosis of RA, cardiovascular risk management should be considered in future clinical practice.