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.

Augmentation Index in Connective Tissue Diseases

“…Tumor necrosis factor alpha (TNF-α) antagonists reduced the AIx, but this improvement was influenced by the clinical response and age. On the other hand, PWV independently improved after TNF-α [46].…”

“…In RA, TNF-α antagonists reduced the AIx. However, the clinical response and age influenced this improvement [46]. In patients with hyperuricemia or gout, allopurinol reduced the AIx and PWV [48].…”

The association of psoriasis and hypertension: focusing on anti‐inflammatory therapies and immunological mechanisms

“…performed a 24‐h ambulatory pressure test for 16 patients with RAon infliximab therapy, and showed that BP significantly decreased during the day 27 . Furthermore, a meta‐analysis of patients with RA showed that infliximab may improve aortic stiffness, as evaluated by aortic pulse wave velocity and augmentation index 28 …”

Arterial stiffness, cognitive impairment and dementia: confounding factor or real risk?

“…A lack of AIx reduction by TNF therapy (Van Doornum et al 2005;Pieringer et al 2010) or even of aortic PWV (Capkin et al 2012) seen by other studies, brought into question the benefits of this approach for correcting arterial stiffness in rheumatoid arthritis patients (Mathieu et al 2013). However, two recent meta-analyses conclude in favour of anti-TNF therapy by showing that most studies show a positive effect on PWV, which is a more direct measure of stiffness than AIx (Dulai et al 2012;Vlachopoulos et al 2017).…”