Background In the general population several serological biomarkers, for example phospholipase A2 group 7 (PLA2G7), macrophage inhibitory cytokine 1 (MIC-1), soluble CD40 ligand (sCD40L), myeloperoxidase (MPO) and interleukin 18 (IL-18), have been found to be associated with unstable atherosclerotic plaques and hence with an increased risk of cardiovascular disease (CVD). These biomarkers are not well studied among patients with rheumatoid arthritis (RA). After five years of follow-up in patients with a recent onset of RA, we have found sub-clinical atherosclerosis, when measured as intima media thickness (IMT) and flow-mediated dilation (FMD), to be more progressive than in controls.
Objectives The aim of the present study was to investigate whether this sub-clinical atherosclerosis could be associated with serological biomarkers of unstable plaques.
Methods Patients from northern Sweden diagnosed with early RA are followed in an ongoing prospective study of co-morbidity. From these patients a subgroup aged ≤60 years (n=71), was consecutively included for measurements of IMT of a. carotis communis and FMD of a. brachialis. The ultrasound measurements were taken at inclusion (T0) and after 5 years (T5). 40 age/sex matched controls were included. The patients were clinically assessed (DAS28, TJC, SJC, DMARDs, ESR and CRP) and blood was drawn from all individuals at T0 and T5 for analysis of cholesterol, HDL-cholesterol, triglycerides, PLA2G7, MIC-1, sCD40L, MPO and IL-18. SCORE and Reynolds Risk Score were calculated at T0 and T5. Larsen score was calculated on x-rays taken at inclusion.
Results At inclusion as well after 5 years, i.e. at T0 and T5, patients with RA had significantly higher levels of MIC-1 (1773 vs. 1216 at T0 and 1941 vs 1331 at T5, p<0.05) and IL-18 (334 vs 286, p<0.05, at T0 and 356 vs 303, p=0.062, at T5) compared with the controls. There were no difference between patients with RA and controls regarding any of the other biomarkers measured. In simple linear regression models at T0 among patients with RA the biomarkers were significantly associated with several other variables at T0: PLA2G7 with IMT, FMD, male sex, HDL-cholestrol (inversely), SCORE, Reynolds Risk score as well as the Larsen score (p<0.05); IL-18 with systolic and diastolic blood pressure as well as Reynolds Risk score (p<0.05); sCD40L with CRP (p<0.01).
In the same simple regression models but after 5 years of follow up the biomarkers were significantly associated with other variables at T5: PLA2G7 with cholesterol, HDL-cholestrol (inversely), BMI and Reynolds Risk score at T5 (p<0.05); MIC-1 with IMT, smoking, age, BMI, SCORE as well as Reynolds Risk score (p<0.05); MPO with systolic blood pressure as well as BMI (p<0.05); sCD40L with area under the curve for CRP over 60 months (p=0.05).
Conclusions Among patients with RA, followed prospectively over 5 years, biomarkers of unstable plaques were associated with sub-clinical atherosclerosis as well as with traditional CVD risk factors and inflammation. This might, in part, clarify the increased risk of CVD among patients with RA.
Disclosure of Interest None Declared
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