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

Effects of Treatment With Biological Agents on Endothelial Glycocalyx,Arterial Elastic Properties, Coronary Flow, Myocardial Deformation and Twisting in Psoriasis. Comparative Study With Patients With CAD or Untreated Hypertension.

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: pulse wave velocity (PWVc) augmentation index (AI) central systolic blood pressure (cSBP) (Complior, Alam Medical and Arteriograph,TensioMed) flow-mediated dilation of the brachial artery (FMD) carotid intima-media thickness (IMT) by ultrasonography coronary flow reserve of the LAD (CFR) by Doppler echocardiography 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 . 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. Fetuin serum levels, markers of oxidative stress such as malondialdehyde (MDA) serum levels, protein carbonyls aw well as thrombosis and inflammation biomarkers

Comparison of effect (improvement or deterioration) of treatment with biological vs. non biological agents on endothelial function in psoriasis

Comparison of effect (improvement or deterioration) of treatment with biological agents (anti-tumor necrosis factor-a, anti-interleukin 12/23, anti-interleukin 17A, or apremilast regimen) with the effects of cyclosporine on endothelial function as assessed by flow mediated dilatation of the brachial artery, coronary flow reserve and endothelial glycocalyx thickness

Comparison of effect (improvement or deterioration) of treatment with biological vs. non biological agents on vascular function in psoriasis

Comparison of effect (improvement or deterioration) of treatment with biological agents (anti-tumor necrosis factor-a, anti-interleukin 12/23, anti-interleukin 17A, or apremilast regimen) with the effects of cyclosporine on vascular function as assessed by pulse wave velocity, augmentation index and central aortic blood pressure,

Comparison of effect (improvement or deterioration) of treatment with biological vs. non biological agents on cardiac function in psoriasis

Comparison of effect (improvement or deterioration) of treatment with biological agents (anti-tumor necrosis factor-a, anti-interleukin 12/23 ,anti-interleukin 17A, or apremilast regimen) with the effects of cyclosporine on cardiac function as assessed by longitudinal myocardial deformation, twisting and untwisting of the left ventricle

Differences in endothelial function between psoriasis and normal controls, and similarities in endothelial function between psoriasis and coronary artery disease patients and untreated hypertension patients before and after 4 week of anti-inflammatory treatment in patients with psoriasis .The following parameters will be compared among the study subgroups endothelial function as assessed by flow mediated dilatation of the brachial artery, coronary flow reserve and endothelial glycocalyx thickness

Differences in vascular function between psoriasis and normal controls, and similarities in vascular function between psoriasis and coronary artery disease patients and untreated hypertension patients before and after 4 week of anti-inflammatory treatment in patients with psoriasis .The following parameters will be compared among the study subgroups vascular function as assessed by pulse wave velocity, augmentation index and central aortic blood pressure,

Differences in cardiac function between psoriasis and normal controls, and similarities in cardiac function between psoriasis and coronary artery disease patients and untreated hypertension patients before and after 4 week of anti-inflammatory treatment in patients with psoriasis The following parameters will be compared among the study subgroups cardiac function as assessed by longitudinal myocardial deformation, twisting and untwisting of the left ventricle

Effects of anti-inflammatory treatment on myocardial infarction, stroke, hospitalization because of heart failure, and cardiovascular death

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

Ikonomidis I, Pavlidis G, Lambadiari V, Rafouli-Stergiou P, Makavos G, Thymis J, Kostelli G, Varoudi M, Katogiannis K, Theodoropoulos K, Katsimbri P, Parissis J, Papadavid E. Endothelial glycocalyx and microvascular perfusion are associated with carotid intima-media thickness and impaired myocardial deformation in psoriatic disease. J Hum Hypertens. 2022 Dec;36(12):1113-1120. doi: 10.1038/s41371-021-00640-2. Epub 2021 Nov 25.

Ikonomidis I, Papadavid E, Makavos G, Andreadou I, Varoudi M, Gravanis K, Theodoropoulos K, Pavlidis G, Triantafyllidi H, Moutsatsou P, Panagiotou C, Parissis J, Iliodromitis E, Lekakis J, Rigopoulos D. Lowering Interleukin-12 Activity Improves Myocardial and Vascular Function Compared With Tumor Necrosis Factor-a Antagonism or Cyclosporine in Psoriasis. Circ Cardiovasc Imaging. 2017 Sep;10(9):e006283. doi: 10.1161/CIRCIMAGING.117.006283.