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

 -  patients with psoriasis

 -  Age and sex matched patients with CAD, with untreated hypertension and healthy
 subjects

 Exclusion Criteria:

 -  for psoriasis patients were presence of wall motion abnormalities and ejection
 fraction ≤ 50%, psoriatic arthritis, history of acute coronary syndrome, familial
 hyperlipidemia, insulin dependent-diabetes mellitus, chronic obstructive pulmonary
 disease or asthma, moderate or severe valvular heart disease, primary cardiomyopathies
 and malignant tumors. CAD was excluded in psoriasis patients by absence of clinical
 history, angina and reversible myocardial ischemia, as assessed by dobutamine stress
 echocardiography or thallium scintigraphy

 -  regarding the group of CAD patients, we only included patients without history of ST
 elevation myocardial infarction in order to exclude the presence of transmural scar
 compromising myocardial function indices. Thus, CAD patients with wall motion
 abnormalities and ejection fraction of ≤ 50% were excluded. In addition, exclusion
 criteria, were history of acute coronary syndrome without ST-segment elevation within
 the last year, familial hyperlipidemia, insulin dependent-diabetes mellitus, chronic
 obstructive pulmonary disease or asthma, moderate or severe valvular heart disease,
 primary cardiomyopathies and malignant tumor

 -  in normal controls, CAD was excluded by the presence of normal ECG, absence of
 clinical history and absence of reversible ischemia by means of treadmill test or
 dobutamine stress echocardiography