The effect of TNF-a antagonists on aortic stiffness and wave reflections: a meta-analysis

Abstract

Patients with rheumatoid arthritis (RA) have higher aortic stiffness and cardiovascular risk. Tumor necrosis factor alpha (TNF-a) antagonists reduce inflammation in RA and are indicated for the treatment of patients with severe active rheumatoid disease. However, it is debatable if they have favorable effects on cardiovascular health. The present meta-analysis evaluates the effect of TNF-a antagonists on aortic stiffness and wave reflections, predictors of cardiovascular events and mortality, in RA patients. A search of PubMed, Cohrane, and Embase databases was conducted to identify studies into the effect of TNF-a antagonists on aortic stiffness in RA patients. Aortic stiffness and wave reflections were assessed by aortic (carotid-femoral [cf]) pulse wave velocity (PWV) and augmentation index (AIx), respectively. cfPWV significantly improved following TNF-a antagonist treatment (mean change: -0.53 m/s, 95% CI: -0.833 to -0.218, p = 0.001), independently of age and clinical response to treatment. A more prominent reduction in cfPWV was associated with etanercept/adalimumab (mean difference: -0.62 m/s, 95% CI: -0.968 to -0.272 m/s, p < 0.001) versus infliximab (mean difference: -0.193 m/s, 95% CI: -0.847 to 0.462 m/s, p = 0.564). TNF-a antagonist treatment induced a significant improvement in AIx (mean change: -1.48%, 95% CI: -2.89 to -0.078%, p = 0.039), but this reduction was influenced by age and clinical response to treatment. The balance of evidence suggests that TNF-a antagonists may have a beneficial effect on aortic stiffness and, therefore, on cardiovascular risk. However, larger, longitudinal studies are warranted to confirm such findings.

Keywords: Arterial stiffness; Augmentation index; Pulse wave velocity; Rheumatoid arthritis; TNF-a antagonists.