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

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.

Exercise duration as a determinant of vascular function and antioxidant balance in patients with coronary artery disease.

BACKGROUND: Exercise improves the clinical outcome of patients with coronary artery disease (CAD); however, the ideal exercise duration for each patient remains unclear. OBJECTIVE: To investigate the effects of exercise duration on arterial elastic properties and antioxidant/pro-oxidant mechanisms in patients with CAD. DESIGN, SETTING, PATIENTS, INTERVENTIONS: Sixty male patients with CAD were randomised into two groups, and underwent exercise for 30 min or 60 min in a crossover design with 2 weeks' wash-out period. In all participants aortic and radial blood pressures (BP) and arterial elastic properties (augmentation index (AIx)/pulse wave velocity (PWV)) were determined at baseline and 24 h after exercise. Plasma malonyldialdehyde (MDA) and superoxide dismutase (SOD)1 and SOD2 levels were also measured. RESULTS: Exercise had no effect on aortic and radial BP (p=NS for all). Walking for 30 min improved AIx (from 33.79 ± 0.91% to 31.73 ± 0.86%, p<0.001) and PWV (from 9.26 ± 0.95 m/s to 9.06 ± 0.21 m/s, p<0.001), while exercise for 60 min had adverse effects on vascular stiffness (for AIx: from 33.37 ± 0.93% to 33.73 ± 1.05%, p=NS and for PWV: from 9.25 ± 0.19 m/s to 9.37 ± 0.21 m/s, p < 0.05 mainly in older patients). Exercise for 60 min was associated with a significant 20% increase in MDA levels (p<0.05). Exercise had no effects on SOD1 levels, however it significantly increased SOD2 levels after 30 min (from 2.26 ± 0.22 ng/mL to 2.36 ± 0.18 ng/mL, p < 0.05) but not after 60 min (p=NS). Conclusion Shorter exercise duration was associated with favourable antioxidant and vascular effects, while longer exercise blunted these beneficial effects and was accompanied by adverse effects on vascular function, mainly in older coronary patients. Further studies are required to explore the hypothesis that a more individualised approach to the selection of the appropriate exercise programme should be considered for patients with CAD.

PDE5 inhibitors in non-urological conditions.

Phosphodiesterase type-5 (PDE5) inhibitors are widely used as first-line therapy for erectile dysfunction (ED). Their efficacy and safety combined with an increasing understanding of cyclic guanosine monophosphate (cGMP)-regulated mechanisms, have triggered a number of attempts to determine their effects and potential benefits in non-urological conditions. In recent years, extensive and diverse preclinical and clinical evidence has been made available. PDE5 inhibition has shown collateral benefits for a multitude of risk factors or diseases associated with, or accompanying ED. To date, PDE5 inhibition has been shown to be effective for the treatment of idiopathic pulmonary arterial hypertension and both sildenafil and tadalafil are approved for this indication. However, PDE5 inhibitors appear to have the potential of further expanding their indications. Importantly, accumulating data show that the therapeutic potential extends to the cardiovascular, gastrointestinal, cutaneous and nervous system and that these agents may be beneficial in a multitude of conditions such as Raynaud's phenomenon, heart failure, essential hypertension and stroke. PDE5 inhibitors are a conceptually attractive therapeutic class of agents with pleiotropic effects. The present review discusses recent findings regarding the effects of PDE5 inhibitors on non-urological conditions and highlights current and future clinical applications beyond ED.