Clinical improvement in rheumatoid arthritis is associated with healthier microvascular function in patients who respond to antirheumatic therapy.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased cardiovascular (CV) mortality. Microvascular endothelial dysfunction occurs early in the development of CV disease and is worsened by inflammation. The effect of drug treatment for RA on microvascular function has been poorly studied. We assessed the effect of antirheumatic treatment on microvascular endothelial function in patients with RA, particularly to examine responders versus nonresponders to therapy. METHODS: Fifty-one patients with active RA and no previous history of CV disease were assessed at baseline and after 2 and 4 months' therapy with either anti-tumor necrosis factor-alpha drugs (etanercept, n = 27, adalimumab, n = 3) or methotrexate, n = 21. RA disease activity, inflammatory measures, and skin microvascular responses, measured using laser Doppler imaging after iontophoretic delivery of acetylcholine (ACh) and sodium nitroprusside (SNP), were assessed at each study visit. RESULTS: Disease Activity Score (DAS28) decreased significantly from baseline to visit 2 and 3 (6.04 +/- 1.2, 4.34 +/- 1.3, 4 +/- 1.3, respectively; p < 0.0001). Endothelium-dependent (ACh) and independent (SNP) responses for the whole cohort did not improve significantly after drug treatment (p = 0.250, p = 0.062, respectively). When patients who responded to antirheumatic therapy (n = 31) were analyzed, there were significant improvements in both ACh (p = 0.028) and SNP responses (p = 0.019). CONCLUSION: Microvascular endothelial function improves in patients who respond to antirheumatic therapy. These results support the importance of effective therapy for RA patients in terms of CV effects, which might extrapolate to reduced CV events in the future. Clinical trial registration no. ISRCTN57761809.

Etanercept improves inflammation-associated arterial stiffness in rheumatoid arthritis.

OBJECTIVES: Increased arterial stiffness, an independent risk factor for premature coronary artery disease, has been reported in patients with RA. The objectives of this study were first to assess, in patients with RA, the relationship between disease activity, inflammation and augmentation index, which is a combined measure of arterial stiffness and pulse wave reflection. The second objective was to establish any effect anti-rheumatic treatment may have on augmentation index. METHODS: One hundred and forty-eight RA patients with no previous history of cardiovascular disease (CVD) had their augmentation index corrected for a heart rate of 75 beats per minute (AIx@75), and parameters of RA disease activity and CV risk measured. Forty-seven patients were then treated with either MTX (n = 21) or etanercept (ETAN) (n = 26), and assessments were repeated at 2 and 4 months. RESULTS: Patients with high CRP (> 10 mg/l) showed significantly higher mean AIx@75 than those with low CRP (< or = 10 mg/l) (33 +/- 8 vs 30 +/- 8%; P = 0.033). On regression analysis, log(10) CRP (beta = 0.298; P = 0.002), gender (beta = 0.257; P = 0.007), BMI (beta = -0.292; P = 0.004), diastolic blood pressure (beta = 0.260; P = 0.009) and age (beta = 0.194; P = 0.046) were independently associated with AIx@75. Treatment with ETAN (35 +/- 9, 32.5 +/- 1 and 32.5 +/- 8%; P = 0.025) but not MTX (31 +/- 1, 31 +/- 1 and 31 +/- 1%; P = 0.971) attenuated the AIx@75 significantly from baseline to Visits 2 and 3. CONCLUSIONS: Systemic inflammation (CRP) is an independent predictor of arterial stiffness and pulse wave reflection in patients with RA. ETAN but not MTX therapy reduces arterial stiffness and pulse wave reflection and may thus improve CV morbidity in RA.