Effects of Treatment With Biological Agents on Vascular and Cardiac Function in Psoriasis

Psoriasis has been associated with an increasing risk for atherosclerosis. The investigators investigated whether surrogate markers of subclinical atherosclerosis, vascular dysfunction and myocardial dysfunction are impaired in patients with psoriasis compared to normal controls ,coronary artery disease patients and untreated hypertension subjects. The investigators also examined the effect of treatment with biological vs no biological agents on vascular and LV function in psoriasis.

The investigators will compare patients with psoriasis with age and sex matched normal controls as well as patients with angiographically documented CAD and patients with untreated hypertension (HYP) used as positive control groups Patients with psoriasis (PS) will be randomized to receive an anti-tumor necrosis-a (TNF-a) ,an anti- interleukin 12/23 regimen, an interleukin 17A antagonist, apremilast (inhibitor of phosphodiesterase-4) or a cyclosporine regimen. The anti-TNF-agent, Etanercept will be given at a dose 50mg twice weekly for 12 weeks and after then once weekly. The anti-IL12/23 regimen, Ustekinumab will be given at a dose 45 mg at the first visit, at 4 weeks and every 12 weeks if body weight is up to 90 kgr. For body weight \>90kgr dose will be adjusted accordingly. The IL-17A antagonist regimen namely secukinumab 300 mg SC at weeks 0, 1, 2, 3, and 4 and 300 mg SC once monthly afterwards Apremilast will be given at a dose of 30mg orally twice daily Cyclosporine will be administered at a dose 2.5-3mg/kgr daily. At baseline , after 12 weeks and one year of treatment, the investigators will measure: 1. pulse wave velocity (PWVc) augmentation index (AI) central systolic blood pressure (cSBP) (Complior, Alam Medical and Arteriograph,TensioMed) 2. flow-mediated dilation of the brachial artery (FMD) 3. carotid intima-media thickness (IMT) by ultrasonography 4. coronary flow reserve of the LAD (CFR) by Doppler echocardiography 5. E'/A of mitral annular velocities ,LV longitudinal (GLS -%),strain, and strain rate (LongSr-l/s), peak twisting (Tw -deg),peak twisting (Tw-deg/sec)velocity,untwisting at mitral valve opening (unTw) and untwisting (unTw) velocity using speckle tracking echocardiography . 6. Perfused boundary region (PBR)of the sublingual arterial microvessels (ranged from 5-25 microns) using Sideview Darkfield imaging. (Microscan, Glycocheck) .The PBR in microvessels is the cell-poor layer which results from the phase separation between the flowing red blood cells (RBC) and plasma.The PBR includes the most luminal part of glycocalyx that does allow cell penetration. Increased PBR is considered an accurate index of reduced endothelial glycocalyx thickness because of a deeper RBC penetration in the glycocalyx. 7. Fetuin serum levels, markers of oxidative stress such as malondialdehyde (MDA) serum levels, protein carbonyls aw well as thrombosis and inflammation biomarkers