279Inhibition of Interleukin-6 activity by tocilizumab improves arterial stiffness, LV myocardial deformation and endothelial glycocalyx in patients with rheumatoid arthritis

Abstract Background/Introduction Tocilizumab, a humanised monoclonal antibody against the human interleukin-6 receptor, is used for the treatment of rheumatoid arthritis (RA). Purpose We investigated the effects of tocilizumab on arterial function, LV myocardial deformation and endothelial glycocalyx in RA patients. Methods 80 patients with rheumatoid arthritis were randomized to tocilizumab (n=40) or prednisolone (n=40) for 3 months. At baseline and after 3-month treatment we assessed: a) carotid-femoral pulse wave velocity (PWV-Complior SP ALAM), b) LV longitudinal strain (GLS), systolic (LongSr) and diastolic (LongSrE) strain rate using speckle tracking echocardiography, c) perfused boundary region (PBR) of the sublingual arterial microvessels (ranged from 5–25μm) using Sideview Darkfield imaging (Microscan, Glycocheck). Increased PBR is considered an accurate index of reduced endothelial glucocalyx thickness, d) flow mediated dilatation (FMD) of the brachial artery after and percentage difference of FMD (FMD%) after hyperemia, e) coronary flow reserve (CFR) of the LAD using Doppler echocardiography, and f) malondialdehyde (MDA), protein carbonyls (PCs) and C-reactive protein (CRP) plasma levels. Results At baseline, all patients had similar disease activity score and markers of vascular and myocardial function. Compared to baseline, all patients had reduced CRP post treatment, while MDA and PCs levels were reduced only after tocilizumab treatment (p<0.05). The percent decrease of MDA was correlated with percent increase of GLS (p<0.001). Compared to baseline, tocilizumab-treated patients reduced PWV (11±3% vs. 10.3±2m/sec) and PBR (2.11±0.2 vs. 1.95±0.18μm) (Figure 1) and increased GLS (−16.1±2.9 vs. −17.6±2.5%), CFR (2.73±0.8 vs. 3.06±1), and FMD% (5.9±2.9 vs. 11.6±3.6) (p<0.05 for all comparisons). No significant changes were observed among prednisolone-treated patients. Figure 1 Conclusions IL-6 inhibition improves endothelial function and oxidative stress resulting to improved vascular function and LV myocardial deformation.

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Association of impaired endothelial glycocalyx with arterial stiffness, coronary microcirculatory dysfunction, and abnormal myocardial deformation in untreated hypertensives

Journal of Clinical Hypertension ◽

10.1111/jch.13236 ◽

2018 ◽

Vol 20 (4) ◽

pp. 672-679 ◽

Cited By ~ 16

Author(s):

Ignatios Ikonomidis ◽

Astrinos Voumvourakis ◽

George Makavos ◽

Helen Triantafyllidi ◽

George Pavlidis ◽

...

Keyword(s):

Arterial Stiffness ◽

Myocardial Deformation ◽

Endothelial Glycocalyx ◽

Microcirculatory Dysfunction

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P5611Association of impaired endothelial glycocalyx with arterial stiffness, coronary microcirculatory dysfunction and abnormal myocardial deformation in untreated hypertensive patients

European Heart Journal ◽

10.1093/eurheartj/ehy566.p5611 ◽

2018 ◽

Vol 39 (suppl_1) ◽

Author(s):

I Ikonomidis ◽

A Voumvourakis ◽

G Pavlidis ◽

G Makavos ◽

H Triantafyllidi ◽

...

Keyword(s):

Arterial Stiffness ◽

Myocardial Deformation ◽

Endothelial Glycocalyx ◽

Hypertensive Patients ◽

Microcirculatory Dysfunction

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P4455Improvement of arterial stiffness, LV myocardial deformation and endothelial glycocalyx is linked with reduced oxidative stress in diabetic type2 patients after optimization of antidiabetic medication

European Heart Journal ◽

10.1093/eurheartj/ehx504.p4455 ◽

2017 ◽

Vol 38 (suppl_1) ◽

Author(s):

I. Ikonomidis ◽

G. Pavlidis ◽

V. Lambadiari ◽

F. Kousathana ◽

H. Triantafyllidi ◽

...

Keyword(s):

Oxidative Stress ◽

Arterial Stiffness ◽

Myocardial Deformation ◽

Endothelial Glycocalyx ◽

Antidiabetic Medication

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Inhibition of interleukin-6 by tocilizumab improves endothelial glycocalyx and myocardial work index in patients with rheumatoid arthritis

European Heart Journal ◽

10.1093/ehjci/ehaa946.3157 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

I Ikonomidis ◽

G Pavlidis ◽

P Katsimbri ◽

J Thymis ◽

D Birba ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Interleukin 6 ◽

Vascular Function ◽

Myocardial Function ◽

Augmentation Index ◽

Post Treatment ◽

Endothelial Glycocalyx ◽

Work Index ◽

Percent Improvement ◽

Percent Decrease

Abstract Background/Introduction Tocilizumab, an interleukin-6 receptor blocker is used for the treatment of rheumatoid arthritis (RA). Purpose We investigated the effects of tocilizumab on endothelial glycocalyx and myocardial function in patients with RA. Methods Eighty patients with RA (age: 64±9 years) were randomized to tocilizumab (n=40) or prednisolone (n=40)for 3 months. We measured at baseline and 3 months post-treatment: a) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced glycocalyx thickness), b) pulse wave velocity (PWV-Complior), central systolic blood pressure (cSBP) and augmentation index (AI), c) global LV longitudinal strain (GLS), longitudinal systolic (LongSr) and diastolic (LongSrE) strain rate, d) global myocardial work index (GWI), global constructive (GCW) and global wasted work (GWW) using speckle tracking imaging. Results At baseline, all patients had similar disease activity score and markers of vascular and myocardial function. Compared with baseline, patients under tocilizumab had reduced PBR (2.14±0.2 vs. 1.97±0.2μm), PWV (11±3 vs. 10.3±2m/s), cSBP (134±18 vs. 129±16mmHg) and LongSrE (0.91±0.3 vs. 1±0.3 1/s) at 3 months (p<0.05). There were no statistically significant differences in the above measured markers in patients under prednisolone (p>0.05) (Table). Compared with prednisolone, tocilizumab treatment achieved a greater increase of GLS (8.5% vs. 2.4%), GWI (12.2% vs. 2.7%), GCW (10.3% vs. 5.9%) and a greater reduction of GWW (−30% vs. −13%) (p<0.05 for all comparisons), despite a similar reduction in C-reactive protein post-treatment. The percent decrease of PBR was associated with the percent decrease of cSBP (r=0.46), PWV (r=0.37) and reversely related with the percent improvement of GLS (r=−0.43) and GWI (r=−0.39) (p<0.05). Conclusions IL-6 inhibition by tocilizumab improves endothelial and vascular function leading to a greater increase of effective myocardial work compared to prednisolone in patients with RA. Funding Acknowledgement Type of funding source: None

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