Background In the general population several inflammatory cytokines, for example pentraxin3 (ptx3), monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), TNF-receptor 1 (TNFR1), TNFR2, endoglin, VCAM and ICAM, have been found to be associated with an increased risk of cardiovascular disease (CVD). In most studies these biomarkers are elevated in patients with rheumatoid arthritis (RA), however they are not well studied with regard of the development of atherosclerosis among patients with 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 in the patients with RA could be associated with cytokines associated with an increased risk of CVD.
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. 40 age/sex matched controls were included. The ultrasound measurements were taken at inclusion (T0) and after 5 years (T5). 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, ptx3, MCP-1, IL-6. At T5 also s-VCAM, s-ICAM, TNFR1, TNFR2 and endoglin were analysed. SCORE and Reynolds Risk Score were calculated at T0 and T5.
Results At the follow up at 5 years, i.e. at T5, patients with RA had significantly higher levels of ptx3 (0.996 vs 0.69, p<0.05), VCAM (365.7 vs 325.7, p<0.05) and TNFR2 (7369.1 vs 4364.0, p<0.001) 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 T5 among patients with RA the inflammatory cytokines were significantly associated with several other variables at T5: ptx3 with area under the curve (AUC) for DAS28 over 60 months; IL-6 with AUC for CRP over 60 months (p<0.001); MCP-1 with cholesterol (p<0.05); s-ICAM with IMT, FMD (inversely), age and Reynolds Risk score (p<0.01); s-VCAM with Reynolds Risk score (p<0.05); TNFR2 with ESR (p<0.05); endoglin inversely with DAS28 and ESR (p<0.05). None of the cytokines measured at T0 were significantly associated with the atherosclerosis neither at T0 nor at T5.
Conclusions The extent of atherosclerosis among patients with RA after 5 years follow-up was associated with the adhesion molecule s-ICAM. Moreover, several of the inflammatory cytokines associated with an increased risk of CVD in the general population were associated with conventional markers of disease activity among the patients with RA. Again, this emphasise the necessity of an optimal treatment of these patients, also for the prevention of co-morbidities like CVD.
Disclosure of Interest None Declared
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