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3. Diabetes mellitus and cardiovascular risk management in patients with rheumatoid arthritis: an international audit

Author

Semb, Anne Grete, Rollefstad, Silvia, Ikdahl, Eirik, Wibetoe, Grunde, Sexton, Joseph, Crowson, Cindy, van Riel, Piet, Kitas, George, Graham, Ian, Rantapää-Dahlqvist, Solbritt, Karpouzas, George Athanasios, Myasoedova, Elena, Gonzalez-Gay, Miguel A, Sfikakis, Petros P, Tektonidou, Maria G, Lazarini, Argyro, Vassilopoulos, Dimitrios, Kuriya, Bindee, Hitchon, Carol, Stoenoiu, Maria Simona, Durez, Patrick, Pascual-Ramos, Virginia, Galarza-Delgado, Dionicio Angel, Faggiano, Pompilio, Misra, Durga Prasanna, Borg, Andrew A, Mu, Rong, Mirrakhimov, Erkin M, Gheta, Diane, Douglas, Karen, Agarwal, Vikas, Myasoedova, Svetlana, Krougly, Lev, Popkova, Tatiana Valentinovna, Tuchyňová, Alena, Tomcik, Michal, Vrablik, Michal, Lastuvka, Jiri, Horak, Pavel, Medkova, Helena Kaspar, and Kerola, Anne M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Heart Disease, Prevention, Arthritis, Clinical Research, Cardiovascular, Hypertension, Diabetes, Autoimmune Disease, Rheumatoid Arthritis, Inflammatory and immune system, Good Health and Well Being, Arthritis, Rheumatoid, Cardiovascular Diseases, Diabetes Mellitus, Heart Disease Risk Factors, Humans, Risk Factors, arthritis, rheumatoid, hypertension, lipids, cardiovascular diseases, atherosclerosis, SURF-RA collaborators, Clinical sciences
Abstract

The objective was to examine the prevalence of atherosclerotic cardiovascular disease (ASCVD) and its risk factors among patients with RA with diabetes mellitus (RA-DM) and patients with RA without diabetes mellitus (RAwoDM), and to evaluate lipid and blood pressure (BP) goal attainment in RA-DM and RAwoDM in primary and secondary prevention. The cohort was derived from the Survey of Cardiovascular Disease Risk Factors in Patients with Rheumatoid Arthritis from 53 centres/19 countries/3 continents during 2014-2019. We evaluated the prevalence of cardiovascular disease (CVD) among RA-DM and RAwoDM. The study population was divided into those with and without ASCVD, and within these groups we compared risk factors and CVD preventive treatment between RA-DM and RAwoDM. The study population comprised of 10 543 patients with RA, of whom 1381 (13%) had DM. ASCVD was present in 26.7% in RA-DM compared with 11.6% RAwoDM (p

Published
2021

4. Effect of Anti‐S100A4 Monoclonal Antibody Treatment on Experimental Skin Fibrosis and Systemic Sclerosis–Specific Transcriptional Signatures in Human Skin.

Author

Trinh‐Minh, Thuong, Györfi, Andrea‐Hermina, Tomcik, Michal, Tran‐Manh, Cuong, Zhou, Xiang, Dickel, Nicholas, Tümerdem, Bilgesu Safak, Kreuter, Alexander, Burmann, Sven‐Niklas, Borchert, Signe Vedel, Hussain, Rizwan Iqbal, Hallén, Jonas, Klingelhöfer, Jörg, Kunz, Meik, and Distler, Jörg H. W.

Subjects
RNA analysis, BIOLOGICAL models, SKIN diseases, PHOSPHORYLATION, CALCIUM-binding proteins, TREATMENT effectiveness, CELLULAR signal transduction, DESCRIPTIVE statistics, MONOCLONAL antibodies, FIBROSIS, SKIN, MICE, BLEOMYCIN, FIBROBLASTS, ADENOSINE monophosphate, SYSTEMIC scleroderma, GENE expression profiling, ANIMAL experimentation, COLLAGEN, INFLAMMATION, STAT proteins, SEQUENCE analysis, EVALUATION
Abstract

Objective: S100A4 is a DAMP protein. S100A4 is overexpressed in patients with systemic sclerosis (SSc), and levels correlate with organ involvement and disease activity. S100A4−/− mice are protected from fibrosis. The aim of this study was to assess the antifibrotic effects of anti‐S100A4 monoclonal antibody (mAb) in murine models of SSc and in precision cut skin slices of patients with SSc. Methods: The effects of anti‐S100A4 mAbs were evaluated in a bleomycin‐induced skin fibrosis model and in Tsk‐1 mice with a therapeutic dosing regimen. In addition, the effects of anti‐S100A4 mAbs on precision cut SSc skin slices were analyzed by RNA sequencing. Results: Inhibition of S100A4 was effective in the treatment of pre‐established bleomycin‐induced skin fibrosis and in regression of pre‐established fibrosis with reduced dermal thickening, myofibroblast counts, and collagen accumulation. Transcriptional profiling demonstrated targeting of multiple profibrotic and proinflammatory processes relevant to the pathogenesis of SSc on targeted S100A4 inhibition in a bleomycin‐induced skin fibrosis model. Moreover, targeted S100A4 inhibition also modulated inflammation‐ and fibrosis‐relevant gene sets in precision cut SSc skin slices in an ex vivo trial approach. Selected downstream targets of S100A4, such as AMP‐activated protein kinase, calsequestrin‐1, and phosphorylated STAT3, were validated on the protein level, and STAT3 inhibition was shown to prevent the profibrotic effects of S100A4 on fibroblasts in human skin. Conclusion: Inhibition of S100A4 confers dual targeting of inflammatory and fibrotic pathways in complementary mouse models of fibrosis and in SSc skin. These effects support the further development of anti‐S100A4 mAbs as disease‐modifying targeted therapies for SSc. [ABSTRACT FROM AUTHOR]

Published
2024
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6. The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements

Author

Hoffmann-Vold, Anna-Maria, Maher, Toby M, Philpot, Edward E, Ashrafzadeh, Ali, Barake, Rafic, Barsotti, Simone, Bruni, Cosimo, Carducci, Paolo, Carreira, Patricia E, Castellví, Ivan, Del Galdo, Francesco, Distler, Jörg H W, Foeldvari, Ivan, Fraticelli, Paolo, George, Peter M, Griffiths, Bridget, Guillén-Del-Castillo, Alfredo, Hamid, Abdul Monem, Horváth, Rudolf, Hughes, Michael, Kreuter, Michael, Moazedi-Fuerst, Florentine, Olas, Jacek, Paul, Suman, Rotondo, Cinzia, Rubio-Rivas, Manuel, Seferian, Andrei, Tomčík, Michal, Uzunhan, Yurdagül, Walker, Ulrich A, Więsik-Szewczyk, Ewa, and Distler, Oliver

Published
2020
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7. Deciphering miRNA Signatures in Axial Spondyloarthritis: The Link between miRNA-1-3p and Pro-Inflammatory Cytokines

Author

Prokopcova, Aneta, primary, Baloun, Jiri, additional, Bubova, Kristyna, additional, Gregova, Monika, additional, Forejtova, Sarka, additional, Horinkova, Jana, additional, Husakova, Marketa, additional, Mintalova, Katerina, additional, Cervenak, Vladimir, additional, Tomcik, Michal, additional, Vencovsky, Jiri, additional, Pavelka, Karel, additional, and Senolt, Ladislav, additional

Published
2024
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8. Cardiovascular risk in myositis patients compared with the general population.

Author

Oreska, Sabina, Storkanova, Hana, Pekacova, Aneta, Kudlicka, Jaroslav, Tuka, Vladimir, Mikes, Ondrej, Krupickova, Zdislava, Satny, Martin, Chytilova, Eva, Kvasnicka, Jan, Spiritovic, Maja, Hermankova, Barbora, Cesak, Petr, Rybar, Marian, Pavelka, Karel, Senolt, Ladislav, Mann, Herman, Vencovsky, Jiri, Vrablik, Michal, and Tomcik, Michal

Subjects
CARDIOVASCULAR diseases risk factors, MUSCLE diseases, BODY composition, BLOOD pressure, ANKLE brachial index, CAROTID artery diseases, AGE distribution, RISK assessment, PULSE wave analysis, SYMPTOMS, RESEARCH funding, MYOSITIS, LONGITUDINAL method, LIPIDS, DISEASE risk factors, DISEASE complications
Abstract

Objectives We aimed to evaluate cardiovascular (CV) risk in patients with idiopathic inflammatory myopathies (IIM) compared with healthy controls (HC) and to assess its association with disease-specific features. Methods Ninety IIM patients and 180 age-/sex-matched HC were included. Subjects with a history of CV disease (angina pectoris, myocardial infarction and cerebrovascular/peripheral arterial vascular events) were excluded. All participants were prospectively recruited and underwent examinations of carotid intima–media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition. The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE) and its modifications. Results Compared with HC, IIM patients had a significantly higher prevalence of traditional CV risk factors, carotid artery disease (CARD), abnormal ABI and PWV. After propensity score matching (using traditional CV risk factors), the prevalence of CARD and pathological PWV remained significantly higher in IIM than HC. No significant difference in SCORE was observed. The most unfavourable CV risk profile was observed in patients with necrotizing myopathy, especially in statin-induced anti-HMGCR+ patients. The calculated CV risk scores by SCORE, SCORE2 and SCORE multiplied by the coefficient 1.5 (mSCORE) were reclassified according to CIMT and the presence of carotid plaques. SCORE was demonstrated to be most inaccurate in predicting CV risk in IIM. Age, disease activity, lipid profile, body composition parameters and blood pressure were the most significant predictors of CV risk in IIM patients. Conclusion Significantly higher prevalence of traditional risk factors and subclinical atherosclerosis was observed in IIM patients compared with HC. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Cardiovascular risk in myositis patients compared with the general population

Author

Oreska, Sabina, primary, Storkanova, Hana, additional, Pekacova, Aneta, additional, Kudlicka, Jaroslav, additional, Tuka, Vladimir, additional, Mikes, Ondrej, additional, Krupickova, Zdislava, additional, Satny, Martin, additional, Chytilova, Eva, additional, Kvasnicka, Jan, additional, Spiritovic, Maja, additional, Hermankova, Barbora, additional, Cesak, Petr, additional, Rybar, Marian, additional, Pavelka, Karel, additional, Senolt, Ladislav, additional, Mann, Herman, additional, Vencovsky, Jiri, additional, Vrablik, Michal, additional, and Tomcik, Michal, additional

Published
2023
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16. Cardiovascular Risk in Myositis Patients Compared to the General Population: Preliminary Data From a Single-Center Cross-Sectional Study

Author

Oreska, Sabina, primary, Storkanova, Hana, additional, Kudlicka, Jaroslav, additional, Tuka, Vladimir, additional, Mikes, Ondrej, additional, Krupickova, Zdislava, additional, Satny, Martin, additional, Chytilova, Eva, additional, Kvasnicka, Jan, additional, Spiritovic, Maja, additional, Hermankova, Barbora, additional, Cesak, Petr, additional, Rybar, Marian, additional, Pavelka, Karel, additional, Senolt, Ladislav, additional, Mann, Herman, additional, Vencovsky, Jiri, additional, Vrablik, Michal, additional, and Tomcik, Michal, additional

Published
2022
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17. 08.48 Increased body fat but decreased lean body mass and bone mineral density in myositis patients are associated with disease duration, inflammatory status, skeletal muscle involvement and physical activity

Author

Oreska, Sabina, Spiritovic, Maja, Cesak, Petr, Marecek, Ondrej, Storkanova, Hana, Kubinova, Katerina, Klein, Martin, Vernerova, Lucie, Ruzickova, Olga, Becvar, Radim, Pavelka, Karel, Senolt, Ladislav, Mann, Herman, Vencovsky, Jiri, and Tomcik, Michal

Published
2017
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23. Orphan nuclear receptor NR4A1 regulates transforming growth factor-β signaling and fibrosis

Author

Palumbo-Zerr, Katrin, Zerr, Pawel, Distler, Alfiya, Fliehr, Judith, Mancuso, Rossella, Huang, Jingang, Mielenz, Dirk, Tomcik, Michal, Furnrohr, Barbara G., Scholtysek, Carina, Dees, Clara, Beyer, Christian, Kronke, Gerhard, Metzger, Daniel, Distler, Oliver, Schett, Georg, and Distler, Jorg H.W.

Subjects
Fibrosis -- Genetic aspects, Pharmacology, Experimental, Cellular signal transduction -- Genetic aspects, Cell receptors -- Properties, Biological sciences, Health
Abstract

Mesenchymal responses are an essential aspect of tissue repair. Failure to terminate this repair process correctly, however, results in fibrosis and organ dysfunction. Therapies that block fibrosis and restore tissue homeostasis are not yet available for clinical use. Here we characterize the nuclear receptor NR4A1 as an endogenous inhibitor of transforming growth factor-β (TGF-β) signaling and as a potential target for anti-fibrotic therapies. NR4A1 recruits a repressor complex comprising SP1, SIN3A, CoREST, LSD1, and HDAC1 to TGF-β target genes, thereby limiting pro-fibrotic TGF-β effects. Even though temporary upregulation of TGF-β in physiologic wound healing induces NR4A1 expression and thereby creates a negative feedback loop, the persistent activation of TGF-β signaling in fibrotic diseases uses AKT- and HDAC-dependent mechanisms to inhibit NR4A1 expression and activation. Small-molecule NR4A1 agonists can overcome this lack of active NR4A1 and inhibit experimentally-induced skin, lung, liver, and kidney fibrosis in mice. Our data demonstrate a regulatory role of NR4A1 in TGF-β signaling and fibrosis, providing the first proof of concept for targeting NR4A1 in fibrotic diseases., Fibrotic diseases impose a major socioeconomic burden on modern societies and account for up to 45% of deaths in the developed world (1). TGF-β is a master regulator of mesenchymal [...]

Published
2015
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25. Gastrointestinal Involvement in Systemic Sclerosis : Overview, Neglected Aspects, Malnutrition, Body Composition and Management

Author

Tomcik, Michal and Oreska, Sabina

Subjects
Medical
Abstract

Gastrointestinal tract (GIT) involvement is the most common internal organ manifestation and is present in up to 90% of patients with systemic sclerosis (SSc). Clinical manifestations can differ according to the part of the GIT affected, disease course and symptoms. A majority of the symptoms are caused by GIT dysmotility. Up to 8% of SSc patients develop several GIT symptoms, which increase the mortality. Although GIT involvement is rarely the direct cause of death, it can lead to several comorbidities including malnutrition and negative alterations of body composition. These factors have a negative impact on quality of life and increase the mortality. To date, the treatment is rather symptomatic. The pathogenesis of GIT involvement in SSc still remains to be clarified to improve the treatment approaches including intravenous immunoglobulins and microRNA interventions.

Published
2022

32. An international audit of the management of dyslipidaemia and hypertension in patients with rheumatoid arthritis: results from 19 countries

Author

Rollefstad, Silvia, primary, Ikdahl, Eirik, additional, Wibetoe, Grunde, additional, Sexton, Joe, additional, Crowson, Cynthia S, additional, van Riel, Piet, additional, Kitas, George D, additional, Graham, Ian, additional, Dahlqvist, Solbritt Rantapää, additional, Karpouzas, George, additional, Myasoedova, Elena, additional, Gonzalez-Gay, Miguel A, additional, Sfikakis, Petros P, additional, Tektonidou, Maria G, additional, Lazarini, Argyro, additional, Vassilopoulos, Dimitrios, additional, Kuriya, Bindee, additional, Hitchon, Carol A, additional, Stoenoiu, Maria Simona, additional, Durez, Patrick, additional, Pascual-Ramos, Virginia, additional, Galarza-Delgado, Dionicio Angel, additional, Faggiano, Pompilio, additional, Misra, Durga Prasanna, additional, Borg, Andrew, additional, Mu, Rong, additional, Mirrakhimov, Erkin M, additional, Gheta, Diane, additional, Myasoedova, Svetlana, additional, Krougly, Lev, additional, Popkova, Tatiana, additional, Tuchyňová, Alena, additional, Tomcik, Michal, additional, Vrablik, Michal, additional, Lastuvka, Jiri, additional, Horák, Pavel, additional, Medková, Helena, additional, and Semb, Anne Grete, additional

Published
2021
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33. Diabetes mellitus and cardiovascular risk management in patients with rheumatoid arthritis: an international audit.

Author

UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Semb, Anne Grete, Rollefstad, Silvia, Ikdahl, Eirik, Wibetoe, Grunde, Sexton, Joseph, Crowson, Cindy, van Riel, Piet, Kitas, George, Graham, Ian, Rantapää-Dahlqvist, Solbritt, Karpouzas, George Athanasios, Myasoedova, Elena, Gonzalez-Gay, Miguel A, Sfikakis, Petros P, Tektonidou, Maria G, Lazarini, Argyro, Vassilopoulos, Dimitrios, Kuriya, Bindee, Hitchon, Carol, Stoenoiu, Maria Simona, Durez, Patrick, Pascual-Ramos, Virginia, Galarza-Delgado, Dionicio Angel, Faggiano, Pompilio, Misra, Durga Prasanna, Borg, Andrew A, Mu, Rong, Mirrakhimov, Erkin M, Gheta, Diane, Douglas, Karen, Agarwal, Vikas, Myasoedova, Svetlana, Krougly, Lev, Valentinovna Popkova, Tatiana, Tuchyňová, Alena, Tomcik, Michal, Vrablik, Michal, Lastuvka, Jiri, Horak, Pavel, Medkova, Helena Kaspar, Kerola, Anne M, SURF-RA collaborators, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Semb, Anne Grete, Rollefstad, Silvia, Ikdahl, Eirik, Wibetoe, Grunde, Sexton, Joseph, Crowson, Cindy, van Riel, Piet, Kitas, George, Graham, Ian, Rantapää-Dahlqvist, Solbritt, Karpouzas, George Athanasios, Myasoedova, Elena, Gonzalez-Gay, Miguel A, Sfikakis, Petros P, Tektonidou, Maria G, Lazarini, Argyro, Vassilopoulos, Dimitrios, Kuriya, Bindee, Hitchon, Carol, Stoenoiu, Maria Simona, Durez, Patrick, Pascual-Ramos, Virginia, Galarza-Delgado, Dionicio Angel, Faggiano, Pompilio, Misra, Durga Prasanna, Borg, Andrew A, Mu, Rong, Mirrakhimov, Erkin M, Gheta, Diane, Douglas, Karen, Agarwal, Vikas, Myasoedova, Svetlana, Krougly, Lev, Valentinovna Popkova, Tatiana, Tuchyňová, Alena, Tomcik, Michal, Vrablik, Michal, Lastuvka, Jiri, Horak, Pavel, Medkova, Helena Kaspar, Kerola, Anne M, and SURF-RA collaborators

Abstract

The objective was to examine the prevalence of atherosclerotic cardiovascular disease (ASCVD) and its risk factors among patients with RA with diabetes mellitus (RA-DM) and patients with RA without diabetes mellitus (RAwoDM), and to evaluate lipid and blood pressure (BP) goal attainment in RA-DM and RAwoDM in primary and secondary prevention. The cohort was derived from the Survey of Cardiovascular Disease Risk Factors in Patients with Rheumatoid Arthritis from 53 centres/19 countries/3 continents during 2014-2019. We evaluated the prevalence of cardiovascular disease (CVD) among RA-DM and RAwoDM. The study population was divided into those with and without ASCVD, and within these groups we compared risk factors and CVD preventive treatment between RA-DM and RAwoDM. The study population comprised of 10 543 patients with RA, of whom 1381 (13%) had DM. ASCVD was present in 26.7% in RA-DM compared with 11.6% RAwoDM (p<0.001). The proportion of patients with a diagnosis of hypertension, hyperlipidaemia and use of lipid-lowering or antihypertensive agents was higher among RA-DM than RAwoDM (p<0.001 for all). The majority of patients with ASCVD did not reach the lipid goal of low-density lipoprotein cholesterol <1.8 mmol/L. The lipid goal attainment was statistically and clinically significantly higher in RA-DM compared with RAwoDM both for patients with and without ASCVD. The systolic BP target of <140 mm Hg was reached by the majority of patients, and there were no statistically nor clinically significant differences in attainment of BP targets between RA-DM and RAwoDM. CVD preventive medication use and prevalence of ASCVD were higher in RA-DM than in RAwoDM, and lipid goals were also more frequently obtained in RA-DM. Lessons may be learnt from CVD prevention programmes in DM to clinically benefit patients with RA .

Published
2021

37. An international audit of the management of dyslipidaemia and hypertension in patients with rheumatoid arthritis: results from 19 countries

Author

Rollefstad, Silvia, Ikdahl, Eirik, Wibetoe, Grunde, Sexton, Joe, Crowson, Cynthia S, van Riel, Piet, Kitas, George D, Graham, Ian, Dahlqvist, Solbritt Rantapää, Karpouzas, George, Myasoedova, Elena, Gonzalez-Gay, Miguel A, Sfikakis, Petros P, Tektonidou, Maria G, Lazarini, Argyro, Vassilopoulos, Dimitrios, Kuriya, Bindee, Hitchon, Carol A, Stoenoiu, Maria Simona, Durez, Patrick, Pascual-Ramos, Virginia, Galarza-Delgado, Dionicio Angel, Faggiano, Pompilio, Misra, Durga Prasanna, Borg, Andrew, Mu, Rong, Mirrakhimov, Erkin M, Gheta, Diane, Myasoedova, Svetlana, Krougly, Lev, Popkova, Tatiana, Tuchyňová, Alena, Tomcik, Michal, Vrablik, Michal, Lastuvka, Jiri, Horák, Pavel, Medková, Helena, and Semb, Anne Grete

Published
2022
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38. S100A4 is elevated in axial spondyloarthritis:a potential link to disease severity

Author

Sumova, Barbora, Cerezo, Lucie Andres, Hulejova, Hana, Prajzlerova, Klara, Tomcik, Michal, Bubova, Kristyna, Stepan, Jan, Filkova, Maria, Kropackova, Tereza, Grigorian, Mariam, Pavelka, Karel, Vencovsky, Jiri, Senolt, Ladislav, Sumova, Barbora, Cerezo, Lucie Andres, Hulejova, Hana, Prajzlerova, Klara, Tomcik, Michal, Bubova, Kristyna, Stepan, Jan, Filkova, Maria, Kropackova, Tereza, Grigorian, Mariam, Pavelka, Karel, Vencovsky, Jiri, and Senolt, Ladislav

Abstract

BackgroundS100A4 is a member of calcium binding S100 protein family well known for its role in cancer progression and metastasis. Nevertheless, S100A4 also serves as a negative regulator of bone formation. Dickkopf-1 (DKK-1), marker of bone remodelling, is also implicated in the process of syndesmophyte formation in ankylosing spondylitis. The aim of our study was to evaluate plasma levels of S100A4 in patients with axial spondyloarthritis and to determine the potential association of S100A4 with disease severity, clinical manifestations and with bone changes in a cross-sectional study.MethodsFifty-eight patients with axial spondyloarthritis and 40 healthy controls were studied. Biological samples were analysed for S100A4 and Dickkopf-1. Disease activity was assessed according to the Bath Ankylosing Spondylitis Disease Activity Index. C-reactive protein (CRP) was used as a marker of inflammation. Radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS).ResultsThe plasma levels of S100A4 were significantly higher in patients with axial spondyloarthritis compared to heathy controls (p

Published
2020

39. Plasma heat shock protein 90 levels in patients with spondyloarthritis and their relation to structural changes: a cross-sectional study

Author

Bubova, Kristyna, primary, Storkanova, Hana, additional, Oreska, Sabina, additional, Spiritovic, Maja, additional, Hermankova, Barbora, additional, Mintalova, Katerina, additional, Gregova, Monika, additional, Husakova, Marketa, additional, Horinkova, Jana, additional, Forejtova, Sarka, additional, Gatterova, Jindriska, additional, Stolfa, Jiri, additional, Komarc, Martin, additional, Vencovsky, Jiri, additional, Pavelka, Karel, additional, Senolt, Ladislav, additional, and Tomcik, Michal, additional

Published
2021
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