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Yaseen AA, Tumey LN. Advances and challenges in immunosuppressive antibody drug conjugates. Eur J Med Chem 2025; 291:117576. [PMID: 40186891 DOI: 10.1016/j.ejmech.2025.117576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 03/21/2025] [Accepted: 03/26/2025] [Indexed: 04/07/2025]
Abstract
Since the approval of Mylotarg™ in 2000 for acute myeloid leukemia, antibody-drug conjugates (ADCs) have significantly advanced precision medicine, particularly for oncology applications. ADCs combine an antibody, a linker, and a payload to result in a targeted therapeutic that minimizes toxicity resulting from systemic drug exposure. This review explores the innovative application of ADC technology towards immunosuppressive therapeutics, primarily focusing on antibody-mediated delivery of glucocorticoids (GCs). Despite their potent anti-inflammatory effects, the clinical use of GCs is limited by adverse systemic effects including osteoporosis, high blood sugar, adrenal insufficiency, weight gain, and glaucoma. Therefore, targeted delivery via ADCs presents a promising strategy to enhance therapeutic efficacy while reducing toxicity. Herein, we review the current status of immune-suppressing ADC technology, starting with early investigations of CD163-targeted dexamethasone and moving to the design of ADCs employing next-generation ultra-potent GCs. Additionally, we will discuss the current status of anti-inflammatory ADCs that employ non-glucocorticoid immune-suppressive medications. Throughout, we will highlight preclinical and clinical data that serves to derisk and drive investment in this new therapeutic class. In parallel, we will focus on ADC design principles that illustrate the importance of careful selection of payload, linker, and conjugation technology in this emerging field.
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Affiliation(s)
- Aiman A Yaseen
- Binghamton University, School of Pharmacy and Pharmaceutical Sciences, PO Box 6000, Binghamton, NY, 13902-6000, USA
| | - L Nathan Tumey
- Binghamton University, School of Pharmacy and Pharmaceutical Sciences, PO Box 6000, Binghamton, NY, 13902-6000, USA.
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2
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Zubirán R, Neufeld EB, Dasseux A, Remaley AT, Sorokin AV. Recent Advances in Targeted Management of Inflammation In Atherosclerosis: A Narrative Review. Cardiol Ther 2024; 13:465-491. [PMID: 39031302 PMCID: PMC11333429 DOI: 10.1007/s40119-024-00376-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 06/26/2024] [Indexed: 07/22/2024] Open
Abstract
Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality despite effective low-density lipoprotein cholesterol-targeted therapies. This review explores the crucial role of inflammation in the residual risk of ASCVD, emphasizing its impact on atherosclerosis progression and plaque stability. Evidence suggests that high-sensitivity C-reactive protein (hsCRP), and potentially other inflammatory biomarkers, can be used to identify the inflammatory residual ASCVD risk phenotype and may serve as future targets for the development of more efficacious therapeutic approaches. We review the biological basis for the association of inflammation with ASCVD, propose new therapeutic strategies for the use of inflammation-targeted treatments, and discuss current challenges in the implementation of this new treatment paradigm for ASCVD.
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Affiliation(s)
- Rafael Zubirán
- Lipoprotein Metabolism Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Edward B Neufeld
- Lipoprotein Metabolism Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Amaury Dasseux
- Lipoprotein Metabolism Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Alan T Remaley
- Lipoprotein Metabolism Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Alexander V Sorokin
- Lipoprotein Metabolism Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
- Section of Inflammation and Cardiometabolic Diseases, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
- Section of Lipoprotein Metabolism, Clinical Research Center, National Heart, Lung and Blood Institute, 9000 Rockville Pike, Bldg 10, Room 5-5150, Bethesda, MD, 20892, USA.
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3
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Pofi R, Caratti G, Ray DW, Tomlinson JW. Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad? Endocr Rev 2023; 44:975-1011. [PMID: 37253115 PMCID: PMC10638606 DOI: 10.1210/endrev/bnad016] [Citation(s) in RCA: 64] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 04/25/2023] [Accepted: 05/26/2023] [Indexed: 06/01/2023]
Abstract
It is estimated that 2% to 3% of the population are currently prescribed systemic or topical glucocorticoid treatment. The potent anti-inflammatory action of glucocorticoids to deliver therapeutic benefit is not in doubt. However, the side effects associated with their use, including central weight gain, hypertension, insulin resistance, type 2 diabetes (T2D), and osteoporosis, often collectively termed iatrogenic Cushing's syndrome, are associated with a significant health and economic burden. The precise cellular mechanisms underpinning the differential action of glucocorticoids to drive the desirable and undesirable effects are still not completely understood. Faced with the unmet clinical need to limit glucocorticoid-induced adverse effects alongside ensuring the preservation of anti-inflammatory actions, several strategies have been pursued. The coprescription of existing licensed drugs to treat incident adverse effects can be effective, but data examining the prevention of adverse effects are limited. Novel selective glucocorticoid receptor agonists and selective glucocorticoid receptor modulators have been designed that aim to specifically and selectively activate anti-inflammatory responses based upon their interaction with the glucocorticoid receptor. Several of these compounds are currently in clinical trials to evaluate their efficacy. More recently, strategies exploiting tissue-specific glucocorticoid metabolism through the isoforms of 11β-hydroxysteroid dehydrogenase has shown early potential, although data from clinical trials are limited. The aim of any treatment is to maximize benefit while minimizing risk, and within this review we define the adverse effect profile associated with glucocorticoid use and evaluate current and developing strategies that aim to limit side effects but preserve desirable therapeutic efficacy.
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Affiliation(s)
- Riccardo Pofi
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK
| | - Giorgio Caratti
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK
| | - David W Ray
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK
- NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK
- Oxford Kavli Centre for Nanoscience Discovery, University of Oxford, Oxford OX37LE, UK
| | - Jeremy W Tomlinson
- Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford OX3 7LE, UK
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4
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So H, Lam TO, Meng H, Lam SHM, Tam LS. Time and dose-dependent effect of systemic glucocorticoids on major adverse cardiovascular event in patients with rheumatoid arthritis: a population-based study. Ann Rheum Dis 2023; 82:1387-1393. [PMID: 37487608 DOI: 10.1136/ard-2023-224185] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 06/29/2023] [Indexed: 07/26/2023]
Abstract
OBJECTIVES Cardiovascular event (CVE) risk in rheumatoid arthritis (RA) was increased by glucocorticoids (GC) use. Whether there is a threshold dose and duration of GC use beyond which will increase CVE rate remains controversial. We studied the time-varying effect of GC and its dose on the risk of incident major adverse cardiovascular events (MACE) in patients with RA. METHODS Patients with RA without MACE at baseline were recruited from a Hong Kong citywide database from 2006 to 2015 and followed till 2018. The primary outcome was the first occurrence of an MACE. Cox regression and inverse probability treatment weighting analyses with time-varying covariates were used to evaluate the association of GC and MACE, adjusting for demographics, traditional CV risk factors, inflammatory markers and the usage of antirheumatic drugs. RESULTS Among 12 233 RA patients with 105 826 patient-years of follow-up and a mean follow-up duration of 8.7 years, 860 (7.0%) developed MACE. In the time-varying analyses after controlling for confounding factors, a daily prednisolone dose of ≥5 mg significantly increased the risk of MACE (erythrocyte sedimentation rate model: HR 2.02, 95% CI 1.72 to 2.37; C reactive protein model: HR 1.87, 95% CI 1.60 to 2.18), while a daily dose below 5 mg was not associated with MACE risk, compared with no GC use. In patients receiving daily prednisolone ≥5 mg, the risk of incident MACE was increased by 7% per month. CONCLUSIONS GC was associated with a duration and dose-dependent increased risk of MACE in patients with RA. Very low dose prednisolone (<5 mg daily) did not appear to confer excessive CV risk.
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Affiliation(s)
- Ho So
- Department of Medicine & Therapeutics, The Chinese University, Hong Kong, Hong Kong
| | - Tsz On Lam
- Department of Medicine & Therapeutics, The Chinese University, Hong Kong, Hong Kong
| | - Huan Meng
- Department of Medicine & Therapeutics, The Chinese University, Hong Kong, Hong Kong
| | - Steven Ho Man Lam
- Department of Medicine & Therapeutics, The Chinese University, Hong Kong, Hong Kong
| | - Lai-Shan Tam
- Department of Medicine & Therapeutics, The Chinese University, Hong Kong, Hong Kong
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5
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Omer MM, Alam M, Rawat A, Lakhdhir F, Alhneif M, Rabadia D, Wei CR, Hirani S. Meta-Analysis on the Impact of Inflammatory Rheumatological Conditions on Outcomes Following Acute Coronary Syndrome. Cureus 2023; 15:e49376. [PMID: 38146576 PMCID: PMC10749408 DOI: 10.7759/cureus.49376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/23/2023] [Indexed: 12/27/2023] Open
Abstract
Inflammatory rheumatological conditions, also known as inflammatory rheumatic conditions (IRC), constitute a category of autoimmune and inflammatory ailments primarily affecting the musculoskeletal system, encompassing the joints, muscles, and connective tissues. The objective of this meta-analysis is to evaluate the impact of inflammatory rheumatological conditions (IRC) on post-acute coronary syndrome (ACS) outcomes. This study was performed as per the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. The PubMed, Web of Science, and Scopus databases were searched by two authors without any language constraints from January 1, 2015, to October 15, 2023. The primary outcome assessed in this meta-analysis was all-cause mortality. Other outcomes included myocardial infarction and revascularization. A total of 11 studies were included in this meta-analysis. The risk of all-cause mortality was significantly higher in patients with IRC compared to non-IRC patients (RR: 1.12, 95% CI: 1.00 to 1.26, p-value: 0.04). There is a significantly higher risk of myocardial infarction and revascularization in patients with IRC as opposed to those without IRC. Furthermore, while there was a higher risk of stroke in the IRC group compared to the non-IRC group, this disparity did not reach statistical significance. Future research should focus on specific inflammatory rheumatoid conditions, a comprehensive evaluation of cardiovascular events, and targeted interventions to enhance patient outcomes in this vulnerable population.
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Affiliation(s)
| | - Morshed Alam
- Internal Medicine, Chittagong Medical College, Chittagong, BGD
| | - Anurag Rawat
- Interventional Cardiology, Himalayan Institute of Medical Sciences, Dehradun, IND
| | - Fahad Lakhdhir
- Adult Cardiology, National Institute of Cardiovascular Diseases, Karachi, PAK
| | | | - Dhaval Rabadia
- Medicine, Surat Municipal Institute of Medical Education and Research, Surat, IND
| | - Calvin R Wei
- Research and Development, Shing Huei Group, Taipei, TWN
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Bedeković D, Bošnjak I, Šarić S, Kirner D, Novak S. Role of Inflammatory Cytokines in Rheumatoid Arthritis and Development of Atherosclerosis: A Review. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1550. [PMID: 37763669 PMCID: PMC10534747 DOI: 10.3390/medicina59091550] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/20/2023] [Accepted: 08/23/2023] [Indexed: 09/29/2023]
Abstract
Uncontrolled chronic inflammation results in cardiovascular disease and early death. In this review, we studied the impact of rheumatoid arthritis on the cardiovascular system, including the early and accelerated development of atherosclerosis and its clinical manifestations, focusing on the inflammatory mechanisms leading to arterial wall damage, rapid atherosclerotic plaque formation, and thrombosis. Furthermore, the effect of medications used to treat rheumatoid arthritis on the cardiovascular system was studied. The effect of chronic inflammation and medication on traditional cardiovascular risk factors is not the main subject of this review. We observed that uncontrolled chronic inflammation and some medications directly impact all the stages of atherosclerosis. In conclusion, reducing inflammation and maintaining long-term remission in rheumatoid arthritis may prevent early atherosclerosis. We believe that this review will encourage a better interdisciplinary approach to the management of these patients and further research in this field.
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Affiliation(s)
- Dražen Bedeković
- Department of Cardiovascular Diseases Internal Medicine Clinic, University Hospital Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (I.B.); (S.Š.); (D.K.)
- Faculty of Medicine Osijek, Department of Internal Medicine, Josip Juraj Strossmayer University, J. Huttlera 4, 31000 Osijek, Croatia
| | - Ivica Bošnjak
- Department of Cardiovascular Diseases Internal Medicine Clinic, University Hospital Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (I.B.); (S.Š.); (D.K.)
| | - Sandra Šarić
- Department of Cardiovascular Diseases Internal Medicine Clinic, University Hospital Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (I.B.); (S.Š.); (D.K.)
- Faculty of Medicine Osijek, Department of Internal Medicine, Josip Juraj Strossmayer University, J. Huttlera 4, 31000 Osijek, Croatia
| | - Damir Kirner
- Department of Cardiovascular Diseases Internal Medicine Clinic, University Hospital Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (I.B.); (S.Š.); (D.K.)
- Faculty of Medicine Osijek, Department of Internal Medicine, Josip Juraj Strossmayer University, J. Huttlera 4, 31000 Osijek, Croatia
| | - Srđan Novak
- Department of Rheumatology and Clinical Immunology, University Hospital Rijeka, Braće Branchetta 20/1, 51000 Rijeka, Croatia;
- Faculty of Medicine Rijeka, Department of Internal Medicine, University of Rijeka, Braće Branchetta 20/1, 51000 Rijeka, Croatia
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Yaginuma H, Saito Y, Sato T, Yamashita D, Matsumoto T, Suzuki S, Wakabayashi S, Kitahara H, Sano K, Kobayashi Y. Clinical characteristics and outcomes of patients with chronic systemic inflammatory disease in acute myocardial infarction. PLoS One 2023; 18:e0289794. [PMID: 37616328 PMCID: PMC10449159 DOI: 10.1371/journal.pone.0289794] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Accepted: 07/21/2023] [Indexed: 08/26/2023] Open
Abstract
BACKGROUND Chronic systemic inflammatory diseases (CSIDs) such as rheumatoid arthritis (RA) are reportedly associated with an increased risk of ischemic cardiovascular events including acute myocardial infarction (MI). However, data are limited on clinical characteristics and ischemic and bleeding outcomes after acute MI in patients with CSIDs. METHODS This bi-center registry included a total of 1001 patients with acute MI undergoing percutaneous coronary intervention. CSIDs included inflammatory rheumatological conditions (RA, systemic lupus erythematosus, vasculitis, etc.) and organ-specific diseases (chronic hepatitis, psoriasis, inflammatory bowel disease, etc.). The primary endpoint was net adverse clinical events (NACE), a composite of ischemic (all-cause death, MI, and ischemic stroke) and major bleeding (Bleeding Academic Research Consortium type 3 or 5) events, during hospitalization and after discharge. RESULTS Of the 1001 patients, 58 (5.8%) had CSIDs. The proportion of women was higher in patients with CSIDs than those without (37.9% vs. 22.1%, p = 0.009). During the hospitalization, no significant differences in the primary endpoint of NACE were observed between patients with and without CSIDs (10.3% vs. 12.7%, p = 0.84). During the median follow-up of 42.6 months after discharge, patients with CSIDs had a higher risk of NACE (22.5% vs. 10.1%, p = 0.01) than those without, mainly driven by an increased risk of ischemic events (18.4% vs. 8.4%, p = 0.03). CONCLUSIONS A small but significant proportion of patients with acute MI (5.8%) had CSIDs. While the incidence of in-hospital events was similar, patients with CSIDs had worse outcomes after discharge, suggesting that further clinical investigations and therapeutic approaches are needed in this patient subset.
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Affiliation(s)
- Hiroaki Yaginuma
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Yuichi Saito
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Takanori Sato
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Daichi Yamashita
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Tadahiro Matsumoto
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Sakuramaru Suzuki
- Department of Cardiovascular Medicine, Eastern Chiba Medical Center, Togane, Japan
| | - Shinichi Wakabayashi
- Department of Cardiovascular Medicine, Eastern Chiba Medical Center, Togane, Japan
| | - Hideki Kitahara
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Koichi Sano
- Department of Cardiovascular Medicine, Eastern Chiba Medical Center, Togane, Japan
| | - Yoshio Kobayashi
- Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
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Kim KN, LaRiviere M, Macduffie E, White CA, Jordan-Luft MM, Anderson E, Ziegler M, Radcliff JA, Jones J. Use of Glucocorticoids in Patients With Cancer: Potential Benefits, Harms, and Practical Considerations for Clinical Practice. Pract Radiat Oncol 2023; 13:28-40. [PMID: 35917896 DOI: 10.1016/j.prro.2022.07.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 07/13/2022] [Accepted: 07/22/2022] [Indexed: 01/10/2023]
Abstract
PURPOSE Glucocorticoids are commonly used in patients with cancer for symptom relief or as part of their anticancer treatment. Despite their frequent use, indications and dosing regimens are not exclusively evidence-based and can come with a multitude of adverse effects, some of which can be life-threatening. The objective of this review is to update our current state of knowledge on the use of glucocorticoids in adult patients with cancer. METHODS AND MATERIALS A comprehensive literature review (1949-2022) was conducted using search terms "glucocorticoids," "corticosteroids," and "cancer." Information was organized by main concepts including indications, potential benefits, and prevention and management of common side effects of glucocorticoid therapy, in addition to appropriate dosing and taper regimens. RESULTS Glucocorticoids can be highly effective in improving outcomes and quality of life in patients with cancer. Their uses include management of disease manifestations, symptoms, and complications of cancer treatment. The lowest effective dose should be used and treatment duration should be minimized as clinically feasible. Side effects can be minimized by careful monitoring, continued assessment of benefits versus harms, and preventative measures for expected side effects. CONCLUSIONS This review provides general principles and practical recommendations on the use of glucocorticoids in patients with cancer. Further prospective studies on the outcomes of patients on glucocorticoids may help guide practice.
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Affiliation(s)
- Kristine N Kim
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
| | - Michael LaRiviere
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Emily Macduffie
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Caitlin A White
- Department of Medicine, Division of Endocrinology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Mary M Jordan-Luft
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Eleanor Anderson
- Department of Psychiatry, Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Matthew Ziegler
- Department of Medicine, Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Jacob A Radcliff
- Department of Pharmacy, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Joshua Jones
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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Boukhris M, Dupire N, Dousset B, Pradel V, Virot P, Magne J, Aboyans V. Management and long-term outcomes of patients with chronic inflammatory diseases experiencing ST-segment elevation myocardial infarction: The SCALIM registry. Arch Cardiovasc Dis 2022; 115:647-655. [PMID: 36372664 DOI: 10.1016/j.acvd.2022.09.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 09/15/2022] [Accepted: 09/20/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND Patients with chronic inflammatory diseases (CIDs) are at increased risk of cardiovascular events. However, the prognostic impact of CID after an acute coronary event has been poorly studied. AIMS To examine the effect of history of CID on long-term outcome in patients with ST-segment elevation myocardial infarction (STEMI). METHODS We analysed data from SCALIM, a regional registry that prospectively enrolled patients with STEMI between June 2011 and May 2019. The presence of CID (including inflammatory bowel diseases, rheumatic conditions, inflammatory skin diseases, multiple sclerosis, vasculitis and autoimmune diseases) was identified. The primary outcome was all-cause death. Secondary outcomes were cardiovascular death, myocardial infarction, ischaemic stroke, peripheral vascular events and rehospitalization for cardiovascular conditions. RESULTS Data from 1941 patients with STEMI (mean age 64.8±14.1 years, 75.1% men) were analyzed. The prevalence of any CID was 4.6% (n=89). After a mean follow-up of 3.4±2.6 years, the overall death rate was 16.2%, with similar 5-year survival between patients with and without CID (74.2% vs. 81.9%, respectively; P=0.121), with no significant mortality excess (hazard ratio: 1.15, 95% confidence interval: 0.73-1.82; P=0.55). However, among CID patients, 35 (39.3%) were on corticosteroid therapy and showed decreased 5-year survival (52.8% vs. 89.5% without corticosteroids; P=0.001). We found no increased rate of secondary endpoints, except for peripheral vascular events (5-year survival free of peripheral events: 93.3% vs. 98.6% in those without CID; P=0.005). CONCLUSIONS Approximately 1 in 20 patients with STEMI has CID. We found no effect of CID on long-term survival. However, patients on corticosteroid therapy appeared to have higher rates of death during follow-up. Whether this finding is related to the use of corticosteroids or to the more progressive nature of their condition warrants further investigation.
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Affiliation(s)
- Marouane Boukhris
- Department of Cardiology, Dupuytren-2 University Hospital, 87042 Limoges, France
| | - Nicolas Dupire
- Department of Cardiology, Dupuytren-2 University Hospital, 87042 Limoges, France
| | - Benjamin Dousset
- Department of Cardiology, Dupuytren-2 University Hospital, 87042 Limoges, France
| | - Valérie Pradel
- Department of Cardiology, Dupuytren-2 University Hospital, 87042 Limoges, France
| | - Patrice Virot
- Department of Cardiology, Dupuytren-2 University Hospital, 87042 Limoges, France
| | - Julien Magne
- Department of Cardiology, Dupuytren-2 University Hospital, 87042 Limoges, France; EpiMaCT, Inserm 1094 & IRD 270, Limoges University, 87000 Limoges, France
| | - Victor Aboyans
- Department of Cardiology, Dupuytren-2 University Hospital, 87042 Limoges, France; EpiMaCT, Inserm 1094 & IRD 270, Limoges University, 87000 Limoges, France.
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10
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Oreska S, Storkanova H, Kudlicka J, Tuka V, Mikes O, Krupickova Z, Satny M, Chytilova E, Kvasnicka J, Spiritovic M, Hermankova B, Cesak P, Rybar M, Pavelka K, Senolt L, Mann H, Vencovsky J, Vrablik M, Tomcik M. Cardiovascular Risk in Myositis Patients Compared to the General Population: Preliminary Data From a Single-Center Cross-Sectional Study. Front Med (Lausanne) 2022; 9:861419. [PMID: 35602501 PMCID: PMC9118331 DOI: 10.3389/fmed.2022.861419] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 03/28/2022] [Indexed: 11/24/2022] Open
Abstract
Background Idiopathic inflammatory myopathies (IIM) are associated with systemic inflammation, limited mobility, and glucocorticoid therapy, all of which can lead to metabolism disturbances, atherogenesis, and increased cardiovascular (CV) risk. The aim of this study was to assess the CV risk in IIM patients and healthy controls (HC), and its association with disease-specific features. Methods Thirty nine patients with IIM (32 females; mean age 56; mean disease duration 4.8 years; dermatomyositis: n = 16, polymyositis: n = 7, immune-mediated necrotizing myopathy: n = 8, anti-synthetase syndrome: n = 8) and 39 age-/sex-matched HC (32 females, mean age 56) without rheumatic diseases were included. In both groups, subjects with a history of CV disease (angina pectoris, myocardial infarction, cerebrovascular, and peripheral arterial vascular events) were excluded. Muscle involvement, disease activity, and tissue damage were evaluated (Manual Muscle Test-8, Myositis Intention to Treat Activity Index, Myositis Damage Index). Comorbidities and current treatment were recorded. All participants underwent examinations of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition (by densitometry and bioelectric impedance). The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE, charts for the European population) and its modifications. Results Compared to HC, there was no significant difference in IIM patients regarding blood pressure, ABI, PWV, CIMT, and the risk of fatal CV events by SCORE or SCORE2, or subclinical atherosclerosis (CIMT, carotid plaques, ABI, and PWV). The calculated CV risk scores by SCORE, SCORE2, and SCORE multiplied by the coefficient 1.5 (mSCORE) were reclassified according to the results of carotid plaque presence and CIMT; however, none of them was demonstrated to be significantly more accurate. Other significant predictors of CV risk in IIM patients included age, disease duration and activity, systemic inflammation, lipid profile, lean body mass, and blood pressure. Conclusions No significant differences in CV risk factors between our IIM patients and HC were observed. However, in IIM, CV risk was associated with age, disease duration, duration of glucocorticoid therapy, lipid profile, and body composition. None of the currently available scoring tools (SCORE, SCORE2, mSCORE) used in this study seems more accurate in estimating CV risk in IIM.
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Affiliation(s)
- Sabina Oreska
- Institute of Rheumatology, Prague, Czechia.,Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czechia
| | - Hana Storkanova
- Institute of Rheumatology, Prague, Czechia.,Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czechia
| | - Jaroslav Kudlicka
- 3rd Department of Internal Medicine, General University Hospital and 1st Faculty of Medicine, Charles University, Prague, Czechia
| | - Vladimir Tuka
- 3rd Department of Internal Medicine, General University Hospital and 1st Faculty of Medicine, Charles University, Prague, Czechia
| | - Ondrej Mikes
- 3rd Department of Internal Medicine, General University Hospital and 1st Faculty of Medicine, Charles University, Prague, Czechia
| | - Zdislava Krupickova
- 3rd Department of Internal Medicine, General University Hospital and 1st Faculty of Medicine, Charles University, Prague, Czechia
| | - Martin Satny
- 3rd Department of Internal Medicine, General University Hospital and 1st Faculty of Medicine, Charles University, Prague, Czechia
| | - Eva Chytilova
- 3rd Department of Internal Medicine, General University Hospital and 1st Faculty of Medicine, Charles University, Prague, Czechia
| | - Jan Kvasnicka
- 3rd Department of Internal Medicine, General University Hospital and 1st Faculty of Medicine, Charles University, Prague, Czechia
| | - Maja Spiritovic
- Institute of Rheumatology, Prague, Czechia.,Department of Physiotherapy, Faculty of Physical Education and Sport, Charles University, Prague, Czechia
| | - Barbora Hermankova
- Department of Physiotherapy, Faculty of Physical Education and Sport, Charles University, Prague, Czechia
| | - Petr Cesak
- Department of Human Movement Laboratory, Faculty of Physical Education and Sport, Charles University, Prague, Czechia
| | - Marian Rybar
- Faculty of Mathematics and Physics, Charles University, Prague, Czechia
| | - Karel Pavelka
- Institute of Rheumatology, Prague, Czechia.,Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czechia
| | - Ladislav Senolt
- Institute of Rheumatology, Prague, Czechia.,Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czechia
| | - Herman Mann
- Institute of Rheumatology, Prague, Czechia.,Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czechia
| | - Jiri Vencovsky
- Institute of Rheumatology, Prague, Czechia.,Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czechia
| | - Michal Vrablik
- 3rd Department of Internal Medicine, General University Hospital and 1st Faculty of Medicine, Charles University, Prague, Czechia
| | - Michal Tomcik
- Institute of Rheumatology, Prague, Czechia.,Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czechia
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11
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Ahmed M, Maliyakkal AM. Non-ST-Segment Elevation Myocardial Infarction Shortly After Starting Steroid Replacement Therapy in a Patient With Adrenal Insufficiency. Cureus 2022; 14:e25061. [PMID: 35719802 PMCID: PMC9201412 DOI: 10.7759/cureus.25061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/16/2022] [Indexed: 11/17/2022] Open
Abstract
Adrenal insufficiency is a rare disorder that results from etiological factors affecting either the hypothalamic-pituitary axis or the adrenal gland itself. Studies have associated an inherently increased risk of cardiovascular events with this condition. It is treated with exogenous steroid supplementation. However, in recent years, there have been an increasing number of reports regarding the potential of steroid therapy to precipitate acute cardiac events. However, this risk is generally assumed to be dose-dependent and could be absent in patients receiving low-dose glucocorticoid treatment. We present a case of a 71-year-old woman who was admitted to our institution with bilateral lower limb swelling. Blood investigation revealed hypoalbuminemia and hyponatremia. Upon further evaluation she was diagnosed to have adrenal insufficiency and was started on hydrocortisone replacement therapy; however, the patient developed non-ST-segment elevation myocardial infarction (NSTEMI) and acute pulmonary edema a few days after starting steroid replacement therapy. Here, we discuss the possible association between hydrocortisone use and the development of acute cardiac events.
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12
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Al-Mohrej OA, Prada C, Leroux T, Shanthanna H, Khan M. Pharmacological Treatment in the Management of Glenohumeral Osteoarthritis. Drugs Aging 2022; 39:119-128. [DOI: 10.1007/s40266-021-00916-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/16/2021] [Indexed: 11/03/2022]
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13
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Anyfanti P, Dara A, Angeloudi E, Bekiari E, Dimitroulas T, Kitas GD. Monitoring and Managing Cardiovascular Risk in Immune Mediated Inflammatory Diseases. J Inflamm Res 2021; 14:6893-6906. [PMID: 34934338 PMCID: PMC8684400 DOI: 10.2147/jir.s276986] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 11/20/2021] [Indexed: 01/03/2023] Open
Abstract
Cardiovascular disease (CVD) is common in immune-mediated inflammatory diseases (IMIDs) and it is predominately attributed to the interplay between chronic inflammation and traditional CVD risk factors. CVD has significant impact on the survival of patients with IMIDs as it is associated with increased morbidity and mortality. Despite recommendations for monitoring and managing CVD in patients with IMIDs, the individual CVD risk assessment remains problematic as CVD risk calculators for the general population consistently underestimate the risk in patients with IMIDs. Application of new technologies utilizing artificial intelligence techniques have shown promising potential for tailoring predictive medicine to the individual patient, but further validation of their role in clinical decision-making is warranted. In the meantime, individuals with IMIDs should be encouraged to adopt behavioral interventions targeting at modifiable lifestyle CVD risk factors, whereas rheumatologists need to be well aware of the unfavorable effects of antirheumatic medication on various CVD risk factors and outcomes. In the current paper, we aim to provide an overview of current and emerging strategies for mitigating CVD risk in patients with IMIDs, based on a practical approach.
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Affiliation(s)
- Panagiota Anyfanti
- Second Medical Department, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Athanasia Dara
- Fourth Department of Internal Medicine, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Elena Angeloudi
- Second Medical Department, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Eleni Bekiari
- Second Medical Department, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Theodoros Dimitroulas
- Fourth Department of Internal Medicine, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - George D Kitas
- Department of Rheumatology, Russells Hall Hospital, Dudley Group NHS Foundation Trust, Dudley, UK.,School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
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14
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Ocon AJ, Reed G, Pappas DA, Curtis JR, Kremer JM. Short-term dose and duration-dependent glucocorticoid risk for cardiovascular events in glucocorticoid-naive patients with rheumatoid arthritis. Ann Rheum Dis 2021; 80:1522-1529. [PMID: 34215644 DOI: 10.1136/annrheumdis-2021-220577] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 06/22/2021] [Indexed: 11/03/2022]
Abstract
OBJECTIVES Rheumatoid arthritis (RA), along with glucocorticoid use, is associated with cardiovascular disease. Cardiovascular safety of glucocorticoids in RA is controversial and may be related to dose and duration of use. We determined if initiating glucocorticoids in steroid-naive RA patients would increase cardiovascular event (CVE) risk in a dose and duration-dependent manner over short-term intervals. METHODS Patients enrolled in CorEvitas (formerly Corrona) RA registry. Cox proportional-hazards models estimated adjusted HRs (aHR) for incident CVE in patients who initiated glucocorticoid treatment, adjusting for RA duration, traditional cardiovascular risk factors and time-varying covariates: Clinical Disease activity Index, disease-modifying antirheumatic drugs use and prednisone-equivalent use. Glucocorticoid use assessed current daily dose, cumulative dose and duration of use over rolling intervals of preceding 6 months and 1 year. RESULTS 19 902 patients met criteria. 1106 CVE occurred (1.66/100 person-years). Increased aHR occurred at current doses of ≥5-9 mg 1.56 (1.18-2.06) and ≥10 mg 1.91 (1.31-2.79), without increased risk at 0-4 mg 1.04 (0.55-1.59). Cumulative dose over preceding 6 months showed increased aHR at 751-1100 mg 1.43 (1.04-1.98) and >1100 mg 2.05 (1.42-2.94), without increased risk at lower doses; duration of use over preceding 6 months exhibited increased aHR for >81 days of use 1.54 (1.08-2.32), without increased risk at shorter durations. One-year analyses were consistent. CONCLUSIONS Over preceding 6-month and 1-year intervals, initiating glucocorticoids in steroid-naïve RA patients is associated with increased risk of CVE at daily doses ≥5 mg and increased cumulative dose and duration of use. No association with risk for CVE was found with daily prednisone of ≤4 mg or shorter cumulative doses and durations.
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Affiliation(s)
- Anthony James Ocon
- Medicine and Allergy, Immunology, Rheumatology, University of Rochester Medical Center, Rochester, New York, USA
| | - George Reed
- Medicine, Preventative and Behavioral Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
- Corrona Research Foundation, LLC, Waltham, MA, USA
| | - Dimitrios A Pappas
- Corrona Research Foundation, LLC, Waltham, MA, USA
- Medicine and Rheumatology, Columbia University, New York, New York, USA
- CorEvitas (formerly CORRONA), LCC, Waltham, Massachusetts, USA
| | - Jeffrey R Curtis
- Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Joel M Kremer
- Corrona Research Foundation, LLC, Waltham, MA, USA
- CorEvitas (formerly CORRONA), LCC, Waltham, Massachusetts, USA
- Medicine and Rheumatology, Albany Medical College, The Center for Rheumatology, LLC, Albany, New York, USA
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15
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Golledge J, Velu R, Quigley F, Jenkins J, Singh TP. Cohort Study Examining the Association of Immunosuppressant Drug Prescription With Major Adverse Cardiovascular and Limb Events in Patients With Peripheral Artery Disease. Ann Vasc Surg 2021; 78:310-320. [PMID: 34537348 DOI: 10.1016/j.avsg.2021.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/21/2021] [Accepted: 07/01/2021] [Indexed: 11/01/2022]
Abstract
AIM Immune activation is strongly implicated in atherosclerotic plaque instability, however, the effect of immunosuppressant drugs on cardiovascular events in patients with peripheral artery disease (PAD) is not known. The aim of this study was to assess whether prescription of one or more immune suppressant drugs was associated with a lower risk of major adverse cardiovascular (MACE; i.e. myocardial infarction, stroke or cardiovascular events) or limb events (MALE; i.e. major amputation or requirement for peripheral revascularization) in patients with PAD. METHODS A total of 1506 participants with intermittent claudication (n = 872) or chronic limb threatening ischemia (CLTI; n = 634) of whom 53 (3.5%) were prescribed one or more immunosuppressant drugs (prednisolone 41; methotrexate 17; leflunomide 5; hydroxychloroquine 3; azathioprine 2; tocilizumab 2; mycophenolate 1; sulfasalazine 1; adalimumab 1) were recruited from 3 Australian hospitals. Participants were followed for a median of 3.9 (inter-quartile range 1.2, 7.3) years. The association of immunosuppressant drug prescription with MACE or MALE was examined using Cox proportional hazard analyses. RESULTS After adjusting for other risk factors, prescription of an immunosuppressant drug was associated with a significantly greater risk of MACE (Hazard ratio, HR, 1.83, 95% confidence intervals, CI, 1.11, 3.01; P = 0.017) but not MALE (HR 1.32, 95% CI 0.90, 1.92; P = 0.153). In a sub-analysis restricted to participants with CLTI findings were similar: MACE (HR 2.44, 95% CI 1.32, 4.51; P = 0.005); MALE (HR 1.38, 95% CI 0.87, 2.19; P = 0.175); major amputation (HR 1.37, 95% CI 0.49, 3.86; P = 0.547). CONCLUSIONS This cohort study suggested that immunosuppressant drug therapy is associated with a greater risk of MACE amongst patients with PAD.
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Affiliation(s)
- Jonathan Golledge
- Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia; The Department of Vascular and Endovascular Surgery, The Townsville University Hospital, Townsville, Queensland, Australia; The Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia.
| | - Ramesh Velu
- The Department of Vascular and Endovascular Surgery, The Townsville University Hospital, Townsville, Queensland, Australia
| | - Frank Quigley
- The Mater Hospital, Townsville, Queensland, Australia
| | - Jason Jenkins
- Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
| | - Tejas P Singh
- Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia; The Department of Vascular and Endovascular Surgery, The Townsville University Hospital, Townsville, Queensland, Australia
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16
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Fazeli MS, Khaychuk V, Wittstock K, Breznen B, Crocket G, Pourrahmat MM, Ferri L. Cardiovascular Disease in Rheumatoid Arthritis: Risk Factors, Autoantibodies, and the Effect of Antirheumatic Therapies. CLINICAL MEDICINE INSIGHTS-ARTHRITIS AND MUSCULOSKELETAL DISORDERS 2021; 14:11795441211028751. [PMID: 34262386 PMCID: PMC8246480 DOI: 10.1177/11795441211028751] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 06/10/2021] [Indexed: 11/21/2022]
Abstract
Objective: To scope the current published evidence on cardiovascular risk factors in rheumatoid arthritis (RA) focusing on the role of autoantibodies and the effect of antirheumatic agents. Methods: Two reviews were conducted in parallel: A targeted literature review (TLR) describing the risk factors associated with cardiovascular disease (CVD) in RA patients; and a systematic literature review (SLR) identifying and characterizing the association between autoantibody status and CVD risk in RA. A narrative synthesis of the evidence was carried out. Results: A total of 69 publications (49 in the TLR and 20 in the SLR) were included in the qualitative evidence synthesis. The most prevalent topic related to CVD risks in RA was inflammation as a shared mechanism behind both RA morbidity and atherosclerotic processes. Published evidence indicated that most of RA patients already had significant CV pathologies at the time of diagnosis, suggesting subclinical CVD may be developing before patients become symptomatic. Four types of autoantibodies (rheumatoid factor, anti-citrullinated peptide antibodies, anti-phospholipid autoantibodies, anti-lipoprotein autoantibodies) showed increased risk of specific cardiovascular events, such as higher risk of cardiovascular death in rheumatoid factor positive patients and higher risk of thrombosis in anti-phospholipid autoantibody positive patients. Conclusion: Autoantibodies appear to increase CVD risk; however, the magnitude of the increase and the types of CVD outcomes affected are still unclear. Prospective studies with larger populations are required to further understand and quantify the association, including the causal pathway, between specific risk factors and CVD outcomes in RA patients.
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Affiliation(s)
| | | | | | - Boris Breznen
- Evidinno Outcomes Research Inc., Vancouver, BC, Canada
| | - Grace Crocket
- Bristol Myers Squibb, Princeton, NJ, USA.,Joulé Inc., Edison, NJ, USA
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17
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Kessler J, Totoson P, Devaux S, Moretto J, Wendling D, Demougeot C. Animal models to study pathogenesis and treatments of cardiac disorders in rheumatoid arthritis: Advances and challenges for clinical translation. Pharmacol Res 2021; 170:105494. [PMID: 34139344 DOI: 10.1016/j.phrs.2021.105494] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 02/08/2021] [Accepted: 02/11/2021] [Indexed: 11/15/2022]
Abstract
Although cardiac diseases such as acute myocardial infarction, heart failure and arrhythmias are the leading cause of cardiovascular complications in rheumatoid arthritis (RA), their pathogenesis is far from being understood and optimal therapeutic options to treat specifically these disorders in RA are lacking. Preclinical studies on animal models of arthritis can help to decipher the complex link between arthritis and the heart, and to identify critical pathways and novel therapeutic targets. This review presented the available data on cardiac disorders in animal models of RA, as well as the current knowledge on pathophysiology and pharmacology of these disorders. Future directions for translational studies in a cardiorheumatic perspective are proposed.
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Affiliation(s)
- Julie Kessler
- PEPITE EA 4267, FHU INCREASE, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France; Service de Rhumatologie, CHU Minjoz, 25000 Besançon, France
| | - Perle Totoson
- PEPITE EA 4267, FHU INCREASE, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France
| | - Sylvie Devaux
- PEPITE EA 4267, FHU INCREASE, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France
| | - Johnny Moretto
- PEPITE EA 4267, FHU INCREASE, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France
| | - Daniel Wendling
- Service de Rhumatologie, CHU Minjoz, 25000 Besançon, France; EA 4266 " Agents Pathogènes et Inflammation ", EPILAB, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France
| | - Céline Demougeot
- PEPITE EA 4267, FHU INCREASE, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France.
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18
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Lim CC, Choo JCJ, Tan HZ, Mok IYJ, Chin YM, Chan CM, Woo KT. Changes in metabolic parameters and adverse kidney and cardiovascular events during glomerulonephritis and renal vasculitis treatment in patients with and without diabetes mellitus. Kidney Res Clin Pract 2021; 40:250-262. [PMID: 34024087 PMCID: PMC8237120 DOI: 10.23876/j.krcp.20.174] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 01/17/2021] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Cardiovascular disease causes significant morbidity and mortality in patients with glomerulonephritis, which is increasingly diagnosed in older individuals who may have diabetes mellitus (DM). We evaluated the impact of DM on metabolic profile, renal and cardiovascular outcomes during treatment and follow-up of individuals with glomerulonephritis. METHODS We performed a retrospective cohort study of 601 consecutive adults with biopsy-proven glomerulonephritis for factors associated with kidney failure, hospitalization for cardiovascular events, and death. Biopsies with isolated diabetic nephropathy were excluded. RESULTS The median patient age was 49.8 years (36.7-60.9 years) with estimated glomerular filtration rate of 56.7 mL/min/1.73 m2 (27.7-93.2 mL/min/1.73 m2). DM was present in 25.4%. The most frequent diagnoses were minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) (29.5%), lupus nephritis (21.3%), immunoglobulin A (IgA) nephropathy (19.1%), and membranous nephropathy (12.1%). The median follow-up was 38.8 months (interquartile range [IQR], 26.8-55.8 months). Among 511 individuals with lupus nephritis, anti-neutrophil cytoplasmic antibody-associated vasculitis, MCD/FSGS, membranous nephropathy, and IgA nephropathy, 52 (10.2%) developed kidney failure at a median 16.4 months (IQR, 2.3-32.2 months), while 29 (5.7%) had cardiovascular-related hospitalizations at 12.9 months (IQR, 4.8-31.8 months) and 31 (6.1%) died at 13.5 months (IQR, 2.5-42.9 months) after diagnosis. Cox regression analysis found that baseline DM was independently associated with kidney failure (adjusted hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.06-4.05, p = 0.03) and cardiovascular-related hospitalization (adjusted HR, 2.69; 95% CI, 1.21-5.98, p = 0.02) but not with mortality. CONCLUSION DM was strongly associated with kidney failure and hospitalization for cardiovascular events in patients with biopsy-proven glomerulonephritis.
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Affiliation(s)
- Cynthia C Lim
- Department of Renal Medicine, Singapore General Hospital, Singapore
| | - Jason C J Choo
- Department of Renal Medicine, Singapore General Hospital, Singapore
| | - Hui Zhuan Tan
- Department of Renal Medicine, Singapore General Hospital, Singapore
| | - Irene Y J Mok
- Department of Renal Medicine, Singapore General Hospital, Singapore
| | - Yok Mooi Chin
- Department of Renal Medicine, Singapore General Hospital, Singapore
| | - Choong Meng Chan
- Department of Renal Medicine, Singapore General Hospital, Singapore
| | - Keng Thye Woo
- Department of Renal Medicine, Singapore General Hospital, Singapore
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19
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Hadwen B, Stranges S, Barra L. Risk factors for hypertension in rheumatoid arthritis patients-A systematic review. Autoimmun Rev 2021; 20:102786. [PMID: 33609791 DOI: 10.1016/j.autrev.2021.102786] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 01/08/2021] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Rheumatoid arthritis is frequently associated with hypertension, which has been shown to increase the risk of cardiovascular disease in these patients. The aim of this systematic review was to explore demographic, behavioural or clinical factors including medication use, associated with incident hypertension in rheumatoid arthritis. METHODS MEDLINE and Scopus were searched for eligible studies that longitudinally investigated incident hypertension or changes in blood pressure (BP) in rheumatoid arthritis patients. Publications were screened by two reviewers according to predetermined inclusion and exclusion criteria. The quality of included studies was assessed via the Newcastle Ottawa Scale and Cochrane Risk of Bias Tool. RESULTS Fourteen studies were deemed eligible and included in this review. The proportion of female subjects ranged from 12 to 87% and the mean age ranged from 47 to 61 years. Regular exercise was associated with a decrease in systolic BP, p = 0.021. Methotrexate was associated with decreased risk of hypertension in two studies. LEF was associated with increased BP in two studies. COX-2 inhibitors were associated with systolic BP and diastolic BP variability (p = 0.009, 0.039, respectively) in one study. Prednisone was found to increase BP and risk of hypertension in three studies. The risk of hypertension in patients taking biologic disease modifying anti-rheumatic drugs (DMARDs) is unclear as some studies report increased BP while others report no difference for biologic compared to conventional DMARDs. CONCLUSION Despite limited longitudinal studies exploring this topic, methotrexate and exercise were shown to protect against risk of hypertension in RA patients, while prednisone and COX-2 inhibitors may increase risk of hypertension.
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Affiliation(s)
- Brook Hadwen
- Department of Epidemiology and Biostatistics, The University of Western Ontario, London, Canada
| | - Saverio Stranges
- Department of Epidemiology and Biostatistics, The University of Western Ontario, London, Canada; Department of Family Medicine, The University of Western Ontario, London, Canada; Lawson Health Research Institute, London, Canada; Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg
| | - Lillian Barra
- Department of Epidemiology and Biostatistics, The University of Western Ontario, London, Canada; Lawson Health Research Institute, London, Canada; Department of Medicine, Division of Rheumatology, The University of Western Ontario, London, Canada.
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20
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Montes EG, Mansani FP, Schafranski MD, Toledo Júnior ADO, Calixto LDF, Costa RLD, Staichak RL, Pinto FM, Berso JDL, Guimarães N, Souza MNBD, Zardo BQ, Vellosa JCR. Relationship between corticotherapy and increased cardiac risk in patients with rheumatoid arthritis. BRAZ J PHARM SCI 2021. [DOI: 10.1590/s2175-97902020000419156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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21
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Bilal M, Qindeel M, Nunes LV, Duarte MTS, Ferreira LFR, Soriano RN, Iqbal HMN. Marine-Derived Biologically Active Compounds for the Potential Treatment of Rheumatoid Arthritis. Mar Drugs 2020; 19:10. [PMID: 33383638 PMCID: PMC7823916 DOI: 10.3390/md19010010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 12/05/2020] [Accepted: 12/10/2020] [Indexed: 02/05/2023] Open
Abstract
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease with a prevalence rate of up to 1% and is significantly considered a common worldwide public health concern. Commercially, several traditional formulations are available to treat RA to some extent. However, these synthetic compounds exert toxicity and considerable side effects even at lower therapeutic concentrations. Considering the above-mentioned critiques, research is underway around the world in finding and exploiting potential alternatives. For instance, marine-derived biologically active compounds have gained much interest and are thus being extensively utilized to confront the confines of in practice counterparts, which have become ineffective for 21st-century medical settings. The utilization of naturally available bioactive compounds and their derivatives can minimize these synthetic compounds' problems to treat RA. Several marine-derived compounds exhibit anti-inflammatory and antioxidant properties and can be effectively used for therapeutic purposes against RA. The results of several studies ensured that the extraction of biologically active compounds from marine sources could provide a new and safe source for drug development against RA. Finally, current challenges, gaps, and future perspectives have been included in this review.
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Affiliation(s)
- Muhammad Bilal
- School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian 223003, China
| | - Maimoona Qindeel
- Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan;
| | - Leonardo Vieira Nunes
- Department of Medicine, Federal University of Juiz de Fora, Juiz de Fora-MG 36036-900, Brazil;
| | | | - Luiz Fernando Romanholo Ferreira
- Graduate Program in Process Engineering, Tiradentes University (UNIT), Av. Murilo Dantas, 300, Farolândia, Aracaju-Sergipe 49032-490, Brazil;
- Institute of Technology and Research (ITP), Tiradentes University (UNIT), Av. Murilo Dantas, 300, Farolândia, Aracaju-Sergipe 49032-490, Brazil
| | - Renato Nery Soriano
- Division of Physiology and Biophysics, Department of Basic Life Sciences, Federal University of Juiz de Fora, Governador Valadares-MG 35010-180, Brazil;
| | - Hafiz M. N. Iqbal
- School of Engineering and Sciences, Tecnologico de Monterrey, Monterrey 64849, Mexico
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22
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Pujades-Rodriguez M, Morgan AW, Cubbon RM, Wu J. Dose-dependent oral glucocorticoid cardiovascular risks in people with immune-mediated inflammatory diseases: A population-based cohort study. PLoS Med 2020; 17:e1003432. [PMID: 33270649 PMCID: PMC7714202 DOI: 10.1371/journal.pmed.1003432] [Citation(s) in RCA: 148] [Impact Index Per Article: 29.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Accepted: 10/29/2020] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Glucocorticoids are widely used to reduce disease activity and inflammation in patients with a range of immune-mediated inflammatory diseases. It is uncertain whether or not low to moderate glucocorticoid dose increases cardiovascular risk. We aimed to quantify glucocorticoid dose-dependent cardiovascular risk in people with 6 immune-mediated inflammatory diseases. METHODS AND FINDINGS We conducted a population-based cohort analysis of medical records from 389 primary care practices contributing data to the United Kingdom Clinical Practice Research Datalink (CPRD), linked to hospital admissions and deaths in 1998-2017. We estimated time-variant daily and cumulative glucocorticoid prednisolone-equivalent dose-related risks and hazard ratios (HRs) of first all-cause and type-specific cardiovascular diseases (CVDs). There were 87,794 patients with giant cell arteritis and/or polymyalgia rheumatica (n = 25,581), inflammatory bowel disease (n = 27,739), rheumatoid arthritis (n = 25,324), systemic lupus erythematosus (n = 3,951), and/or vasculitis (n = 5,199), and no prior CVD. Mean age was 56 years and 34.1% were men. The median follow-up time was 5.0 years, and the proportions of person-years spent at each level of glucocorticoid daily exposure were 80% for non-use, 6.0% for <5 mg, 11.2% for 5.0-14.9 mg, 1.6% for 15.0-24.9 mg, and 1.2% for ≥25.0 mg. Incident CVD occurred in 13,426 (15.3%) people, including 6,013 atrial fibrillation, 7,727 heart failure, and 2,809 acute myocardial infarction events. One-year cumulative risks of all-cause CVD increased from 1.4% in periods of non-use to 8.9% for a daily prednisolone-equivalent dose of ≥25.0 mg. Five-year cumulative risks increased from 7.1% to 28.0%, respectively. Compared to periods of non-glucocorticoid use, those with <5.0 mg daily prednisolone-equivalent dose had increased all-cause CVD risk (HR = 1.74; 95% confidence interval [CI] 1.64-1.84; range 1.52 for polymyalgia rheumatica and/or giant cell arteritis to 2.82 for systemic lupus erythematosus). Increased dose-dependent risk ratios were found regardless of disease activity level and for all type-specific CVDs. HRs for type-specific CVDs and <5.0-mg daily dose use were: 1.69 (95% CI 1.54-1.85) for atrial fibrillation, 1.75 (95% CI 1.56-1.97) for heart failure, 1.76 (95% CI 1.51-2.05) for acute myocardial infarction, 1.78 (95% CI 1.53-2.07) for peripheral arterial disease, 1.32 (95% CI 1.15-1.50) for cerebrovascular disease, and 1.93 (95% CI 1.47-2.53) for abdominal aortic aneurysm. The lack of hospital medication records and drug adherence data might have led to underestimation of the dose prescribed when specialists provided care and overestimation of the dose taken during periods of low disease activity. The resulting dose misclassification in some patients is likely to have reduced the size of dose-response estimates. CONCLUSIONS In this study, we observed an increased risk of CVDs associated with glucocorticoid dose intake even at lower doses (<5 mg) in 6 immune-mediated diseases. These results highlight the importance of prompt and regular monitoring of cardiovascular risk and use of primary prevention treatment at all glucocorticoid doses.
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Affiliation(s)
- Mar Pujades-Rodriguez
- Leeds Institute of Health Sciences, School of Medicine, University of Leeds, Leeds, United Kingdom
| | - Ann W. Morgan
- Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, United Kingdom
- NIHR Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital, Leeds, Leeds, United Kingdom
| | - Richard M. Cubbon
- Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, United Kingdom
| | - Jianhua Wu
- School of Dentistry, University of Leeds, Leeds, United Kingdom
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Do DMARDs and biologic agents protect from cardiovascular disease in patients with inflammatory arthropathies? Autoimmun Rev 2019; 18:102401. [PMID: 31655302 DOI: 10.1016/j.autrev.2019.102401] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Accepted: 07/03/2019] [Indexed: 12/22/2022]
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Aksakal E, Simsek Z, Aksu U, Birdal O, Ateş ES, Kalkan K, Gulcu O, Demirelli S, Aksakal E, Tas H. Acute cardiac effects of high dose steroid treatment: A speckle tracking echocardiography study. JOURNAL OF CLINICAL ULTRASOUND : JCU 2019; 47:351-355. [PMID: 30785648 DOI: 10.1002/jcu.22716] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 01/25/2019] [Accepted: 02/08/2019] [Indexed: 06/09/2023]
Abstract
PURPOSE High-dose steroid therapy (HDST) has frequent side-effects that appear at its cessation and depend on its dose. However, there is a lack of studies about the acute effects of HDST on cardiac function in adult patients. METHODS We included in this study 30 patients who underwent HDST (intravenously at doses ranging from 250 to 1000 mg) and 30 healthy control subjects with similar demographic and clinical characteristics, between September and December 2016. Echocardiographic measurements were made before and during the first 3 hours after the end of treatment, and results were compared between patients and controls. RESULTS There was no difference in baseline biochemical and echocardiographic characteristics between the patient and control groups. While left ventricular global longitudinal strain (LVGLS) and strain rate E were higher after treatment, no significant change was observed in conventional echocardiographic variables. CONCLUSIONS LVGLS, but not conventional echocardiographic variables, showed an increase in cardiac systolic function at the acute phase of HDST.
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Affiliation(s)
- Emrah Aksakal
- Department of Cardiology, Erzurum Education and Research Hospital, Erzurum, Turkey
| | - Ziya Simsek
- Department of Cardiology, Kayseri Education and Research Hospital, Kayseri, Turkey
| | - Uğur Aksu
- Department of Cardiology, Erzurum Education and Research Hospital, Erzurum, Turkey
| | - Oguzhan Birdal
- Department of Cardiology, Atatürk University Faculty of Medicine, Erzurum, Turkey
| | - Esma Selva Ateş
- Department of Cardiology, Atatürk University Faculty of Medicine, Erzurum, Turkey
| | - Kamuran Kalkan
- Department of Cardiology, Erzurum Education and Research Hospital, Erzurum, Turkey
| | - Oktay Gulcu
- Department of Cardiology, Erzurum Education and Research Hospital, Erzurum, Turkey
| | - Selami Demirelli
- Department of Cardiology, Erzurum Education and Research Hospital, Erzurum, Turkey
| | - Enbiya Aksakal
- Department of Cardiology, Atatürk University Faculty of Medicine, Erzurum, Turkey
| | - Hakan Tas
- Department of Cardiology, Atatürk University Faculty of Medicine, Erzurum, Turkey
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Vranic A, Pruner I, Veselinovic M, Soutari N, Petkovic A, Jakovljevic V, Antovic A. Assessment of hemostatic disturbances in women with established rheumatoid arthritis. Clin Rheumatol 2019; 38:3005-3014. [PMID: 31209709 DOI: 10.1007/s10067-019-04629-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 05/15/2019] [Accepted: 05/29/2019] [Indexed: 12/31/2022]
Abstract
OBJECTIVES This study was aimed to assess hemostatic disturbances in female patients with established rheumatoid arthritis (RA) in relation to menopausal status and disease activity. METHOD Ninety women were included in the study, 42 patients and 48 age-matched healthy controls. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. Two global hemostatic assays were employed, namely endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). The parameters of the ETP assay (ETP, C-max, t-lag, t-max) and OHP assay (overall coagulation potential (OCP) and overall fibrinolytic potential (OFP)) were assessed. Moreover, the parameters of the fibrin clot (lag time, Max Abs, and slope) were measured by clot turbidity and scanning electron microscopy (SEM). Both patients and controls were divided into four subgroups according to menopause status. RESULTS The premenopausal controls differed significantly from all other subgroups in terms of diminished levels of ETP (p = 0.02), C-max (p = 0.01), OCP (p = 0.02), OHP (p = 0.001), and Max Abs (p = 0.008), while OFP (p = 0.0001) was increased. This tendency was not seen in the premenopausal RA patients compared with the postmenopausal RA patients. SEM images showed denser clots composed of thinner fibers in samples from RA patients. The disease activity measured by DAS28 correlated with OCP and OHP (r = 0.54; p = 0.001 and r = 0.44; p = 0.003, respectively) indicating persistent hypercoagulable condition in the whole group of RA patients. CONCLUSIONS Our results point towards coagulation activation in premenopausal women with established RA. The patients were well characterized, which enabled assessment in a real-life setting. Key Points • Extensive assessment points towards persistent coagulation activation in premenopausal women with established rheumatoid arthritis. • Impaired thrombin generation and fibrin formation are associated with menopause in healthy women, while rheumatoid arthritis closes the gap within patients regarding menopause. • Fibrin morphology is unfavorably altered and fibrinolysis is decreased in patients with established rheumatoid arthritis. • Increased activity of thrombin activatable fibrinolysis inhibitor (TAFI) may contribute to impaired fibrinolysis in patients with rheumatoid arthritis.
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Affiliation(s)
- Aleksandra Vranic
- Faculty of Medical Sciences, Department of Pharmacy, University of Kragujevac, Kragujevac, Serbia
| | - Iva Pruner
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Mirjana Veselinovic
- Faculty of Medical Sciences, Department of Internal Medicine, University of Kragujevac, Kragujevac, Serbia
| | - Nida Soutari
- Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden
| | - Anica Petkovic
- Faculty of Medical Sciences, Department of Pharmacy, University of Kragujevac, Kragujevac, Serbia
| | - Vladimir Jakovljevic
- Faculty of Medical Sciences, Department of Physiology, University of Kragujevac, Kragujevac, Serbia.,1st Moscow State Medical, University IM Sechenov, Department of Human Pathology, Moscow, Russia
| | - Aleksandra Antovic
- Department of Medicine, Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden. .,Academic Specialist Center, Center for Rheumatology, Stockholm Health Services, Stockholm, Sweden.
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Luís M, Freitas J, Costa F, Buttgereit F, Boers M, Jap DS, Santiago T. An updated review of glucocorticoid-related adverse events in patients with rheumatoid arthritis. Expert Opin Drug Saf 2019; 18:581-590. [PMID: 31056959 DOI: 10.1080/14740338.2019.1615052] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Glucocorticoids represent a cornerstone in the treatment of rheumatoid arthritis. Their effect as a disease-modifying treatment in rheumatoid arthritis is well established. Despite this, the risk of adverse events of glucocorticoids, especially in high doses and over a long time, is constantly highlighted. Data on the prevalence and impact of glucocorticoid-related adverse effects in rheumatoid arthritis is needed, therefore, to be regularly revisited. AREAS COVERED In this review, our primary aim was to provide an update of evidence from randomized controlled trials and observational cohort studies on the safety of glucocorticoid treatment in rheumatoid arthritis. Our secondary aim was to provide a critical overview of the concerns raised with both study designs - randomized clinical trials versus nonrandomized observational studies - regarding the assessment of the safety of glucocorticoids in rheumatoid arthritis. EXPERT OPINION In the meantime, adherence to recommendations and consensus on standardized methodologies for monitoring and reporting adverse events is essential to improve our knowledge and competence in the best management of glucocorticoids.
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Affiliation(s)
- Mariana Luís
- a Rheumatology Department , Centro Hospitalar e Universitário de Coimbra , Coimbra , Portugal
| | - João Freitas
- a Rheumatology Department , Centro Hospitalar e Universitário de Coimbra , Coimbra , Portugal
| | - Flávio Costa
- a Rheumatology Department , Centro Hospitalar e Universitário de Coimbra , Coimbra , Portugal
| | - Frank Buttgereit
- b Department of Rheumatology and Clinical Immunology , Charité University Medicine , Berlin , Germany
| | - Maarten Boers
- c Department of Epidemiology and Biostatistics, Amsterdam Rheumatology and Immunology Center , Amsterdam University Medical Centers, Vrije Universiteit Amsterdam , Amsterdam , The Netherlands
| | - Da Silva Jap
- a Rheumatology Department , Centro Hospitalar e Universitário de Coimbra , Coimbra , Portugal.,d Faculty of Medicine , University of Coimbra , Coimbra , Portugal.,e Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine , University of Coimbra , Coimbra , Portugal
| | - Tânia Santiago
- a Rheumatology Department , Centro Hospitalar e Universitário de Coimbra , Coimbra , Portugal.,d Faculty of Medicine , University of Coimbra , Coimbra , Portugal
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Karimifar M, Sepehrifar MS, Moussavi H, Sepehrifar MB, Mottaghi P, Siavash M, Karimifar M. The effects of conventional drugs in the treatment of rheumatoid arthritis on the serum lipids. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2018; 23:105. [PMID: 30693040 PMCID: PMC6327686 DOI: 10.4103/jrms.jrms_869_17] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/14/2017] [Revised: 03/03/2018] [Accepted: 10/08/2018] [Indexed: 11/04/2022]
Abstract
BACKGROUND Rheumatoid arthritis (RA) is a common chronic autoimmune disorder that leads to damage of human joints. There are various treatment approaches in which different drugs are prescribed which have several alterations in serum lipids. This research aimed to study the effect of RA treatments on the serum lipids. MATERIALS AND METHODS Two hundred randomly selected patients with RA were randomly assigned to three different groups. The first group of patients was treated with a combination of prednisolone (PRD) and hydroxychloroquine (HCQ). The second group was treated with three drugs including PRD, HCQ, and methotrexate (MTX). The third group was treated with four medications including PRD, HCQ, MTX, and sulfasalazine. Within each group, the lipid factors such as triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), erythrocyte sedimentation rate, and visual analog scale were measured at the beginning of the experiment and 6 months after exposing the treatments. For each group, we also calculated the Disease Activity Score-28 (DAS-28). The analysis of variance revealed that the overall DAS-28 was significantly different among the three groups. RESULTS In the first group, the level of TG and TC significantly decreased (P = 0.015 and P ≤ 0.001, respectively). In the second group, the level of TG and LDL significantly decreased (P = 0.009). In the third group, the LDL level increased considerably (P < 0.001). The HDL level significantly increased in all three groups (P = 0.012, P = 0.014, and P = 0.028, respectively). CONCLUSION The treatment PRD + HCQ + MTX was more effective in reducing the LDL level and increasing the HDL level. To reduce the risk of cardiovascular diseases in patients with RA, it is important to prescribe the combination of drugs which leads and normalizes the lipid profile levels.
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Affiliation(s)
- Mansoor Karimifar
- Department of Rheumatology, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad S Sepehrifar
- Department of Internal Medicine, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hamidreza Moussavi
- Department of Rheumatology, Noor and Aliasghar Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad B Sepehrifar
- Department of Mathematics and Statistics, Mississippi State University, Starkville, Mississippi, USA
| | - Peyman Mottaghi
- Department of Rheumatology, Noor and Aliasghar Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mansour Siavash
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mozhgan Karimifar
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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Alten R, Mischkewitz M. New concepts to reduce glucocorticoid toxicity. Joint Bone Spine 2018; 86:715-723. [PMID: 30528678 DOI: 10.1016/j.jbspin.2018.11.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Accepted: 11/28/2018] [Indexed: 12/25/2022]
Abstract
70 years after their first use, low-dose glucocorticoids are a common part of pharmacological rheumatoid arthritis treatment. This is due to their well-proven capacities in symptom severity and disease activity reduction, in particular when combined with a disease-modifying anti-rheumatic drug, such as methotrexate. Nevertheless, glucocorticoid administration, in long-term especially, is also seen critically because of its potential adverse conditions. In order to achieve a reduction in treatment-related adverse events, modern therapy regimes should take into consideration patients' risk factors and therefore be individual. The Glucocorticoid Toxicity Index is a method to measure side effects of glucocorticoid therapy objectively and will be central in future studies comparing different therapy regimes. Such a new therapy regime is modified-release prednisone, which - thanks to a different time of liberation - seems to capable of reducing morning stiffness much more effectively than conventional prednisone, whilst showing similar properties in disease activity reduction and safety. Still, confirmation of these first data in further trials will be necessary. Eventually, other innovative concepts are liposomal glucocorticoids, dissociated agonists of glucocorticoid receptors and intramuscular application of glucocorticoids. Though these approaches appear to be promising, additional research will be required.
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Affiliation(s)
- Rieke Alten
- Schlosspark-Klinik Charité University Medicine Berlin, Heubnerweg, 2, 14059 Berlin, Germany.
| | - Max Mischkewitz
- Schlosspark-Klinik Charité University Medicine Berlin, Heubnerweg, 2, 14059 Berlin, Germany
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Oishi S, Wendling D, Sibilia J, Job-Deslandre C, Guillevin L, Benichou J, Flipo RM, Duquenne C, Guillemin F, Saraux A. Treatment of active rheumatoid arthritis: comparison of patients younger vs older than 75 years (CORPUS cohort). Hum Vaccin Immunother 2018; 14:2612-2617. [PMID: 30230962 PMCID: PMC6314403 DOI: 10.1080/21645515.2018.1522470] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Objectives: Little information is available on the characteristics of elderly patients starting TNFα antagonist treatment for rheumatoid arthritis (RA). The objective of this work was to compare prescription patterns in RA patients younger vs. older than 75 years. Methods: Biologic-naive patients with active RA (DAS28 > 3.2) despite first-line therapy were included between 2007 and 2009 in the prospective, multicentre, longitudinal, observational, population-based CORPUS-RA cohort. TNFα antagonist users were defined as having received at least one TNFα antagonist during the first study year. The groups < 75 years and ≥ 75 years were compared regarding comorbidities, inflammation (CRP and ESR), disease activity (DAS28), disability (HAQ-DI), number of physician visits, and treatment. To verify the impact of the cut off, we also compared patients aged 70 years or more to patients younger than 70 years. Results: Of 543 RA patients, 382 had complete one-year follow-up data, including 114 TNFα antagonist users, 3 (6%) among the 49 patients aged 75 years or over and 111 (32%) of the 333 patients younger than 75 years (p < 0.01). Disease activity in the two age groups was similar at inclusion and after one year. Comorbidities and a history of auto-immunity were more common in the older group. Compared to their younger counterparts, the older patients received glucocorticoids more often (p = 0.003) and synthetic disease-modifying anti-rheumatic drugs less often (p = 0.01). Conclusion: TNFα antagonists are used less often and glucocorticoids more often in elderly patients with active RA compared to their younger counterparts. The fact that this study was performed in 2007–9 is a limitation in terms of relevance to today’s patients and further studies should be conducted in new cohorts of active RA.
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Affiliation(s)
- Sachiyo Oishi
- a Rheumatology department , Centre National de Référence des Maladies Auto-Immunes Rares (CERAINO), CHU Brest , Brest Cedex , France
| | - Daniel Wendling
- b Rheumatology department , Besançon University Hospital, Boulevard Fleming , Besançon , France.,c EA 4266 , Franche-Comté University , Besançon , France
| | - Jean Sibilia
- d Rheumatology department , Hautepierre University Hospital , Strasbourg , France
| | | | - Loic Guillevin
- f Department of Internal Medicine , Cochin-Paris University Hospital , Paris , France
| | - Jacques Benichou
- g Department of Biostatistics and Clinical Research , Rouen University Hospital , Rouen , France.,h INSERM U1219 , University of Rouen , Rouen , France
| | - René Marc Flipo
- i Rheumatology department , Lille University Hospital , Lille , France
| | - Carole Duquenne
- a Rheumatology department , Centre National de Référence des Maladies Auto-Immunes Rares (CERAINO), CHU Brest , Brest Cedex , France
| | - Francis Guillemin
- j INSERM, CIC-EC 1433 , Université de Lorraine, Brabois University Hospital , Vandoeuvre-lès-Nancy , France
| | - Alain Saraux
- k Rheumatology department, Centre National de Référence des Maladies Auto-Immunes Rares (CERAINO), CHU Brest, and INSERM UMR 1227, Laboratoire d'Immunothérapie et Pathologies lymphocytaires B, Labex 'Immunotherapy, Graft, Oncology' , Université de Brest , Brest , Cedex , France
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30
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Roubille C, Rincheval N, Dougados M, Flipo RM, Daurès JP, Combe B. Seven-year tolerability profile of glucocorticoids use in early rheumatoid arthritis: data from the ESPOIR cohort. Ann Rheum Dis 2017; 76:1797-1802. [PMID: 28213564 DOI: 10.1136/annrheumdis-2016-210135] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 01/14/2017] [Accepted: 01/21/2017] [Indexed: 01/04/2023]
Abstract
OBJECTIVE To explore the 7-year tolerability profile of glucocorticoids (GC) for early rheumatoid arthritis (RA). METHODS We examined data for 602 patients with RA from the early arthritis Etude et Suivi des POlyarthrites Indifférenciées Récentes (ESPOIR) cohort (<6 months disease duration) stratified into two groups: with or without GC treatment at least once during follow-up (median 7 years (IQR 0.038-7.65)). The main outcome was a composite of death, cardiovascular disease (including myocardial ischaemia, cerebrovascular accident and heart failure), severe infection and fracture. RESULTS Among the 602 patients with RA (476 women (79%), mean age 48±12 years), 386 with GC (64.1%) received low-dose prednisone (mean 3.1±2.9 mg/day for the entire follow-up): 263 started GC during the first 6 months (68%), and the mean duration of total GC treatment was 1057±876 days. As compared with patients without GC (216 (35.9%)), those with GC showed greater use of non-steroidal anti-inflammatory drugs, synthetic and biological disease-modifying antirheumatic drugs and had more active disease disability, higher C reactive protein and anticitrullinated protein antibody levels. Among 65 events (7 deaths, 14 cardiovascular diseases, 19 severe infections and 25 fractures), 44 and 21 occurred in patients with and without GC (p=0.520). Infections were more frequent, although not significantly, in patients with than without GC (p=0.09). On weighted Cox proportional-hazards analysis, with use of propensity score and inverse-probability-of-treatment weighting, and including age, gender, history of hypertension and GC treatment, outcomes did not differ with and without GC (p=0.520; HR=0.889; 95% CI 0.620 to 1.273). CONCLUSIONS This 7-year analysis of the ESPOIR cohort supports the good safety profile of very low-dose GC for early active RA.
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Affiliation(s)
- Camille Roubille
- Rheumatology Department, Lapeyronie Hospital, Montpellier University, Montpellier, France
- Internal Medicine and Hypertension Department, Lapeyronie Hospital, Montpellier University, Montpellier, France
| | - Nathalie Rincheval
- Rheumatology Department, Lapeyronie Hospital, Montpellier University, Montpellier, France
- Statistiques, University Institute of Clinical Research, EA2415, Montpellier, France
| | - Maxime Dougados
- Paris Descartes University, Rheumatology Department, Cochin Hospital, AP-HP, Paris, France
- INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, France
| | - René-Marc Flipo
- Department of Rheumatology, Roger Salengro Hospital, Lille, France
| | - Jean-Pierre Daurès
- Statistiques, University Institute of Clinical Research, EA2415, Montpellier, France
| | - Bernard Combe
- Rheumatology Department, Lapeyronie Hospital, Montpellier University, Montpellier, France
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Verhoeven F, Totoson P, Maguin-Gaté K, Prigent-Tessier A, Marie C, Wendling D, Moretto J, Prati C, Demougeot C. Glucocorticoids improve endothelial function in rheumatoid arthritis: a study in rats with adjuvant-induced arthritis. Clin Exp Immunol 2017; 188:208-218. [PMID: 28152574 DOI: 10.1111/cei.12938] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/24/2017] [Indexed: 12/15/2022] Open
Abstract
To determine the effect of glucocorticoids (GCs) on endothelial dysfunction (ED) and on traditional cardiovascular (CV) risk factors in the adjuvant-induced arthritis (AIA) rat model. At the first signs of AIA, a high dose (HD) [10 mg/kg/day, intraperitoneally (i.p.), GC-HD] or low dose (LD) (1 mg/kg/day, i.p., GC-LD) of prednisolone was administered for 3 weeks. Endothelial function was studied in aortic rings relaxed with acetylcholine (Ach) with or without inhibitors of nitric oxide synthase (NOS), cyclooxygenase 2 (COX-2), arginase, endothelium derived hyperpolarizing factor (EDHF) and superoxide anions ( O2-°) production. Aortic expression of endothelial NOS (eNOS), Ser1177-phospho-eNOS, COX-2, arginase-2, p22phox and p47phox was evaluated by Western blotting analysis. Arthritis scores, blood pressure, heart rate and blood levels of cytokines, triglycerides, cholesterol and glucose were measured. GC-HD but not GC-LD reduced arthritis score significantly and improved Ach-induced relaxation (P < 0·05). The positive effect of GC-HD resulted from increased NOS activity and EDHF production and decreased COX-2/arginase activities and O2-° production. These functional effects relied upon increased phospho-eNOS expression and decreased COX-2, arginase-2 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression. Despite the lack of effect of GC-LD on ED, it increased NOS and EDHF and down-regulated O2-° pathways but did not change arginase and COX-2 pathways. GC-HD increased triglycerides levels and blood pressure significantly (P < 0·05). Both doses of GCs decreased to the same extent as plasma interleukin (IL)-1β and tumour necrosis factor (TNF)-α levels (P < 0·05). Our data demonstrated that subchronic treatment with prednisolone improved endothelial function in AIA via pleiotropic effects on endothelial pathways. These effects occurred independently of the deleterious cardiometabolic effects and the impact of prednisolone on systemic inflammation.
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Affiliation(s)
- F Verhoeven
- PEPITE EA4267, FHU INCREASE, Université Bourgogne Franche-Comté, Besançon, France.,Service de Rhumatologie, CHRU Besançon, France
| | - P Totoson
- PEPITE EA4267, FHU INCREASE, Université Bourgogne Franche-Comté, Besançon, France
| | - K Maguin-Gaté
- PEPITE EA4267, FHU INCREASE, Université Bourgogne Franche-Comté, Besançon, France
| | | | - C Marie
- INSERM U1093, Université Bourgogne Franche-Comté, Dijon, France
| | - D Wendling
- Service de Rhumatologie, CHRU Besançon, France.,EA 4266, Université Bourgogne Franche-Comté, Besançon, France
| | - J Moretto
- PEPITE EA4267, FHU INCREASE, Université Bourgogne Franche-Comté, Besançon, France
| | - C Prati
- PEPITE EA4267, FHU INCREASE, Université Bourgogne Franche-Comté, Besançon, France.,Service de Rhumatologie, CHRU Besançon, France
| | - C Demougeot
- PEPITE EA4267, FHU INCREASE, Université Bourgogne Franche-Comté, Besançon, France
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Low dose prednisolone and insulin sensitivity differentially affect arterial stiffness and endothelial function: An open interventional and cross-sectional study. Atherosclerosis 2017; 258:34-39. [PMID: 28189039 DOI: 10.1016/j.atherosclerosis.2017.01.033] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 01/17/2017] [Accepted: 01/27/2017] [Indexed: 11/24/2022]
Abstract
BACKGROUND AND AIMS Glucocorticoids could impair vascular function directly, or indirectly by reducing insulin sensitivity. The aim of this study was to determine the direct and indirect effects of acute and chronic low dose prednisolone on arterial stiffness and endothelial function. METHODS Twelve subjects with inflammatory arthritis, who had not taken oral glucocorticoids for ≥6 months, and 12 subjects with inflammatory arthritis, taking chronic (>6 months) low dose (6.3 ± 2.2 mg/day) prednisolone, were studied. Patients not on glucocorticoids underwent measurement of arterial stiffness (pulse wave velocity (PWV)) and endothelial function (reactive hyperaemia index (RHI)) before and after 7-10 days of prednisolone (6 mg/day), to assess the acute effects of prednisolone. Baseline data from patients not on glucocorticoids were compared with patients on long-term prednisolone to assess the chronic effects of prednisolone. Hepatic insulin sensitivity was estimated from percentage suppression of endogenous glucose production and peripheral insulin sensitivity as glucose infusion rate (M/I) during a hyperinsulinaemic-euglycaemic clamp. RESULTS There were no significant changes in PWV with acute (9.2 ± 0.8 vs. 8.9 ± 0.8 m/sec, p = 0.33) or chronic (8.9 ± 0.8 vs. 9.0 ± 0.7 m/sec, p = 0.69) prednisolone. In multiple regression analysis, PWV was negatively associated with M/I during hyperinsulinemic-euglycemic clamp (p = 0.02), but not with suppression of endogenous glucose production (p = 0.15) or glucocorticoid use (p = 0.70). Chronic (2.4 ± 0.2 vs. 1.9 ± 0.1, p = 0.02), but not acute (1.8 ± 0.2 vs. 1.9 ± 0.1, p = 0.24), prednisolone resulted in a higher RHI. CONCLUSIONS Arterial stiffness is not affected by low dose prednisolone per se, but is negatively associated with peripheral insulin sensitivity. Patients with rheumatoid arthritis taking long-term prednisolone had better endothelial function.
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Quinkler M, Ekman B, Marelli C, Uddin S, Zelissen P, Murray RD. Prednisolone is associated with a worse lipid profile than hydrocortisone in patients with adrenal insufficiency. Endocr Connect 2017; 6:1-8. [PMID: 27864317 PMCID: PMC5148794 DOI: 10.1530/ec-16-0081] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Accepted: 11/18/2016] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Prednisolone is used as glucocorticoid replacement therapy for adrenal insufficiency (AI). Recent data indicate that its use in AI is associated with low bone mineral density. Data on risk factors for cardiovascular disease in patients with AI treated with prednisolone are scarce, despite this condition being the predominant cause of excess mortality. We aimed to address this question using real-world data from the European Adrenal Insufficiency Registry (EU-AIR). DESIGN/METHODS EU-AIR, comprising of 19 centres across Germany, the Netherlands, Sweden and the UK, commenced enrolling patients with AI in August 2012. Patients receiving prednisolone (3-6 mg/day, n = 50) or hydrocortisone (15-30 mg/day, n = 909) were identified and grouped at a ratio of 1:3 (prednisolone:hydrocortisone) by matching for gender, age, duration and type of disease. Data from baseline and follow-up visits were analysed. Data from patients with congenital adrenal hyperplasia were excluded. RESULTS Significantly higher mean ± s.d. total (6.3 ± 1.6 vs 5.4 ± 1.1 mmol/L; P = 0.003) and low-density lipoprotein (LDL) cholesterol levels (3.9 ± 1.4 vs 3.2 ± 1.0 mmol/L; P = 0.013) were identified in 47 patients on prednisolone vs 141 receiving hydrocortisone at baseline and at follow-up (P = 0.005 and P = 0.006, respectively). HbA1c, high-density lipoprotein and triglyceride levels, body mass index, systolic and diastolic blood pressure and waist circumference were not significantly different. CONCLUSIONS This is the first matched analysis of its kind. Significantly higher LDL levels in patients receiving prednisolone relative to hydrocortisone could predict a higher relative risk of cardiovascular disease in the former group.
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Affiliation(s)
| | - Bertil Ekman
- Departments of Endocrinology and Medical and Health SciencesLinköping University, Linköping, Sweden
| | | | | | - Pierre Zelissen
- Department of Internal Medicine and EndocrinologyUniversity Medical Center Utrecht, Utrecht, the Netherlands
| | - Robert D Murray
- Department of EndocrinologyLeeds Teaching Hospitals NHS Trust, St James's University Hospital, Leeds, UK
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Abstract
Glucocorticoids (GCs) are widely used anti-inflammatory drugs well known to cause many adverse effects. Still, there is a dearth of data on the long-term cardiovascular effects of GCs in patients with established cardiovascular disease and the effect on atherosclerotic plaque composition. A total of 1894 patients who underwent carotid endarterectomy (CEA), of whom 40 patients received systemic GCs, were included in the Athero-Express Biobank. Atherosclerotic plaque samples and peripheral blood samples were obtained during CEA. Cardiovascular events during 3 years of follow-up were investigated using Cox regression modeling to adjust for possible confounding. Atherosclerotic plaque composition was examined using immunohistochemical staining. Use of GCs at inclusion was associated with markedly increased incidences of ischemic stroke (15.2% vs. 5.9%), composite events (48.5% vs. 26.9%), and cardiovascular death (21.2% vs. 5.7%), as well as an increased risk of cardiovascular death (hazards ratio 2.7, 95% confidence interval, 1.1-6.7) and all-cause death (hazards ratio 2.3, 95% confidence interval, 1.1-4.8) after 2.6 years of follow-up. None of the histological features of atherosclerotic plaques were significantly different in patients using GCs. After CEA, the use of systemic GCs is independently associated with an increased incidence of cardiovascular events and an increased risk of cardiovascular and all-cause death, but not atherosclerotic plaque composition.
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Treat-to-target therapy does not prevent excessive progression of carotid intima media thickness during the first year of therapy in early rheumatoid arthritis. ACTA ACUST UNITED AC 2016; 1:e36-e43. [PMID: 28905017 PMCID: PMC5421530 DOI: 10.5114/amsad.2016.60225] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2016] [Accepted: 05/13/2016] [Indexed: 12/15/2022]
Abstract
Introduction The aim of the study was to investigate the presence of subclinical atherosclerosis and predictors of change in carotid intima-media measures in early rheumatoid arthritis patients (eRA) as compared to chronic RA patients and patients without arthritis. Material and methods Fifty-five consecutive eRA patients were assessed at the time of diagnosis and after 1 year of therapy. Fifty-five sex- and age-matched chronic RA patients and 29 patients without inflammatory disease were used as controls. Carotid artery intima-media thickness (CIMT) and carotid plaques were measured at baseline and after follow-up. In eRA patients ultrasound assessment of hand joints was performed before and after treatment. Carotid artery intima-media thickness was assessed again after 2 years in 44 eRA patients. Results Carotid artery intima-media thickness progression after 1 year of therapy was higher in eRA patients compared to both control groups (p = 0.017) and correlated with symptoms duration (p = 0.017) and DMARD monotherapy (p = 0.015). Ultrasound progression of hand joint erosions was associated with longer symptoms duration (p = 0.006). After 2 years of observation CIMT progression was similar in all examined groups. Conclusions We observed rapid CIMT progression during the first year of RA therapy. Longer symptoms duration and less aggressive therapy were associated with CIMT increase.
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Su CM, Huang CY, Tang CH. Characteristics of resistin in rheumatoid arthritis angiogenesis. Biomark Med 2016; 10:651-60. [PMID: 26867862 DOI: 10.2217/bmm.15.125] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Adipokines have been reported to be involved in the regulation of various physiological processes, including the immune response. Rheumatoid arthritis (RA) is an example of a systemic immune disease that causes chronic inflammation of the synovium and bone destruction in the joint. Recent therapeutic strategies based on the understanding of the role of cytokines and cellular mechanisms in RA have improved our understanding of angiogenesis. On the other hand, endogenous endothelial progenitor cells, which are a population isolated from peripheral blood monocytes have recently been identified as a homing target for pro-angiogeneic factor and vessel formation. In this review, we summarize the effects of common adipokines, such as adiponectin, leptin and resistin in RA pathogenesis and discuss other potential mechanisms of relevance for the therapeutic treatment of RA.
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Affiliation(s)
- Chen-Ming Su
- Department of Biomedical Sciences Laboratory, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China.,Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
| | - Chun-Yin Huang
- Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.,Department of Orthopedic Surgery, China Medical University Beigang Hospital, Yun-Lin County, Taiwan
| | - Chih-Hsin Tang
- Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.,Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.,Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
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Balancing benefits and risks of glucocorticoids in rheumatic diseases and other inflammatory joint disorders: new insights from emerging data. An expert consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Aging Clin Exp Res 2016; 28:1-16. [PMID: 26746234 DOI: 10.1007/s40520-015-0522-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2015] [Accepted: 12/22/2015] [Indexed: 12/26/2022]
Abstract
PURPOSE This consensus review article considers the question of whether glucocorticoid (GC) therapy is still relevant in the treatment of rheumatic diseases, with a particular focus on rheumatoid arthritis (RA), and whether its side effects can be adequately managed. Recent basic and clinical research on the molecular, cellular and clinical effects of GCs have considerably advanced our knowledge in this field. An overview of the subject seems appropriate. METHODS This review is the result of a multidisciplinary expert working group, organised by European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. The recent literature was surveyed and the salient evidence synthetized. RESULTS The pathophysiological basis of RA (and other inflammatory rheumatic diseases) now strongly implicates the adaptive immune system in addition to innate mechanisms. The molecular effect of GCs and differential GC sensitivity is better understood, although exploiting this knowledge is still in its infancy. The newer treatment strategies of early and aggressive control of RA have gr eatly improved clinical outcomes, but improvements are still possible. Newer targeted anti-inflammatory drugs have made an important impact, yet they too are associated with numerous side effects. DISCUSSION Short durations of moderate doses of GCs are generally well tolerated and have a positive benefit/risk ratio. Patients should be assessed for fracture risk and bone preserving agents and be prescribed calcium and vitamin D supplementation. CONCLUSIONS Within a strategy of a disease modifying approach to inflammatory disease, combination therapy including a GC is effective approach.
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Cibor D, Domagala-Rodacka R, Rodacki T, Jurczyszyn A, Mach T, Owczarek D. Endothelial dysfunction in inflammatory bowel diseases: Pathogenesis, assessment and implications. World J Gastroenterol 2016; 22:1067-1077. [PMID: 26811647 PMCID: PMC4716020 DOI: 10.3748/wjg.v22.i3.1067] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 08/24/2015] [Accepted: 11/30/2015] [Indexed: 02/06/2023] Open
Abstract
Endothelial dysfunction is considered one of the etiological factors of inflammatory bowel disease (IBD). An inflammatory process leads to functional and structural changes in the vascular endothelium. An increase of leukocyte adhesiveness and leukocyte diapedesis, as well as an increased vascular smooth muscle tone and procoagulant activity is observed. Structural changes of the vascular endothelium comprise as well capillary and venule remodeling and proliferation of endothelial cells. Hypoxia in the inflammatory area stimulates angiogenesis by up-regulation of vascular endothelial growth factor, fibroblast growth factor and tumor necrosis factor-α. Inflammatory mediators also alter the lymphatic vessel function and impair lymph flow, exacerbating tissue edema and accumulation of dead cells and bacteria. The endothelial dysfunction might be diagnosed by the use of two main methods: physical and biochemical. Physical methods are based on the assessment of large arteries vasodilatation in response to an increased flow and receptors stimulation. Flow-mediated vasodilatation (FMD) is the method that is the most widely used; however, it is less sensitive in detecting early changes of the endothelium function. Most of the studies demonstrated a decrease of FMD in IBD patients but no changes in the carotic intima-media thickness. Biochemical methods of detecting the endothelial dysfunction are based on the assessment of the synthesis of compounds produced both by the normal and damaged endothelium. The endothelial dysfunction is considered an initial step in the pathogenesis of atherosclerosis in the general population. In IBD patients, the risk of cardiovascular diseases is controversial. Large, prospective studies are needed to establish the role of particular medications or dietary elements in the endothelial dysfunction as well to determine the real risk of cardiovascular diseases.
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Holmqvist M, Simard JF, Asplund K, Arkema EV. Stroke in systemic lupus erythematosus: a meta-analysis of population-based cohort studies. RMD Open 2015; 1:e000168. [PMID: 26719816 PMCID: PMC4692049 DOI: 10.1136/rmdopen-2015-000168] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Revised: 09/29/2015] [Accepted: 10/11/2015] [Indexed: 01/08/2023] Open
Abstract
Previous studies of stroke in systemic lupus erythematosus (SLE) have had limited statistical power, combined stroke subtypes into composite outcomes, and lacked a reference population estimate. Therefore, we conducted a systematic review and meta-analysis of cohort studies to summarise the stroke subtype-specific risk in patients with SLE compared to the general population. A systematic search of MEDLINE and EMBASE was performed for cohort studies examining the risk of stroke in SLE and including a general population comparator. Random effects models were used to pool the risk ratio (RR) for stroke. Subgroup analyses were carried out to investigate potential sources of heterogeneity. 10 studies were included which reported RRs for overall stroke (n=5), ischaemic stroke (n=6), intracerebral haemorrhage (n=3) and subarachnoid haemorrhage (n=3). The pooled RR for overall stroke was 2.53 (95% CI 1.96 to 3.26), ischaemic stroke 2.10 (95% CI 1.68 to 2.62), intracerebral haemorrhage 2.72 (95% CI 2.15 to 3.44) and subarachnoid haemorrhage 3.85 (95% CI 3.20 to 4.64). Significant heterogeneity among studies for ischaemic stroke was detected (p=0.002). Relative risk of stroke was highest among individuals younger than 50 years of age. Individuals with SLE have a twofold higher risk of ischaemic stroke, a threefold higher risk of intracerebral haemorrhage, and an almost fourfold higher risk of subarachnoid haemorrhage compared to the general population. Future studies should focus on whether comorbidity and disease flares are related to stroke, when individuals are at the highest risk, and how the targeting of specific groups of patients with SLE may reduce this risk.
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Affiliation(s)
- Marie Holmqvist
- Clinical Epidemiology Unit, Department of Medicine Solna , Karolinska Institute , Stockholm , Sweden
| | - Julia F Simard
- Clinical Epidemiology Unit, Department of Medicine Solna , Karolinska Institute , Stockholm , Sweden ; Division of Epidemiology, Department of Health Research & Policy , Stanford School of Medicine , Stanford, California , USA
| | - Kjell Asplund
- Department of Public Health and Clinical Medicine , Umeå University , Umeå , Sweden
| | - Elizabeth V Arkema
- Clinical Epidemiology Unit, Department of Medicine Solna , Karolinska Institute , Stockholm , Sweden
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Mantel Ä, Holmqvist M, Nyberg F, Tornling G, Frisell T, Alfredsson L, Askling J. Risk Factors for the Rapid Increase in Risk of Acute Coronary Events in Patients With New-Onset Rheumatoid Arthritis: A Nested Case-Control Study. Arthritis Rheumatol 2015; 67:2845-54. [DOI: 10.1002/art.39267] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2014] [Accepted: 06/25/2015] [Indexed: 01/06/2023]
Affiliation(s)
| | | | - Fredrik Nyberg
- University of Gothenburg, Gothenburg, Sweden, and AstraZeneca Research and Development; Mölndal Sweden
| | | | | | | | - Johan Askling
- Karolinska Institute and Karolinska University Hospital; Stockholm Sweden
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Fautrel B, Den Broeder AA. De-intensifying treatment in established rheumatoid arthritis (RA): Why, how, when and in whom can DMARDs be tapered? Best Pract Res Clin Rheumatol 2015; 29:550-65. [PMID: 26697766 DOI: 10.1016/j.berh.2015.09.006] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
As more patients with established rheumatoid arthritis (RA) achieve remission or low disease activity, strategies such as tapering and withdrawal of disease-modifying antirheumatic drugs (DMARDs) are being investigated. In several trials, DMARD discontinuation was associated with a higher risk of relapse, ranging from 56% to 87% at 1 year. Tapering, either by dose reduction or by injection spacing, may limit the risk of relapse. Half-dose etanercept (ETN) versus full-dose continuation was not associated with an increased relapse risk at 1 year in two trials. Progressive antitumor necrosis factor injection spacing was shown to be equivalent to full regimen continuation in terms of persistent flare and disease activity at 18 months in one trial, but not in another one. Reintroduction of a DMARD at previous dose/regimen was usually associated with remission re-induction. The risk of relevant structural damage progression was not increased. Safety improvement has not yet been demonstrated. The annual cost reduction when tapering biologic DMARDs (bDMARDs) was 3500-6000 €/patient. Research questions to be addressed include defining flare that requires reinitiation of treatment, such that patients facilitate the maintenance of remission during tapering by timely communication with their rheumatology team.
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Affiliation(s)
- Bruno Fautrel
- Pierre et Marie Curie University - Paris 6, Sorbonne Universités, GRC-08 (EEMOIS), Paris, France; APHP, Rheumatology Department, Pitié Salpêtrière Hospital, F-75013, Paris, France.
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Molina E, del Rincon I, Restrepo JF, Battafarano DF, Escalante A. Mortality in Rheumatoid Arthritis (RA): factors associated with recording RA on death certificates. BMC Musculoskelet Disord 2015; 16:277. [PMID: 26438345 PMCID: PMC4595199 DOI: 10.1186/s12891-015-0727-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 09/18/2015] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Death certificates can be used to assess disease prevalence and incidence; however, rheumatoid arthritis (RA) often remains unreported in death certificates. We sought to determine to what extent RA is underreported and what demographic and clinical characteristics could predict mention of RA in the death certificate. METHODS We recruited 1328 patients with RA from private, public and military rheumatology practices and followed them prospectively for yearly evaluations. A rheumatologist assessed clinical characteristics of RA and comorbidities at each evaluation. Deaths were identified through family members, other physicians, obituaries and public death databases. All were confirmed with state-issued death certificates. Patients with and without RA in death certificate were compared using bivariate and multivariate analyses. RESULTS By December 2013, 326 deaths had occurred. We received and reviewed death certificates for all confirmed deaths, of which 58 (17.7 %) mentioned RA on the death certificate. Bivariate analysis revealed that younger age, a greater number of deformities, higher Sharp score and lower socioeconomic status were each associated with recording RA. Multivariable analyses revealed that comorbidity [OR (95 % CI) = 0.84 (0.73, 0.97); P = 0.022] was inversely associated with listing RA on the death certificate, while the number of deformities [OR (95 % CI) = 1.04 (1.00, 1.07); P = 0.033] and a certified physician's signature on the death certificate [OR (95 % CI) = 4.79 (1.35, 16.9); P = 0.015] increased likelihood of reporting RA. CONCLUSION In this cohort, RA was not listed in over 80 % of death certificates. Younger patients with fewer comorbidities and more joint deformities were more likely to have RA reported. DISCUSSION RA is often not included in death certificates. The findings of this study suggest that older patients may have a greater number of comorbidities, thus decreasing the likelihood that RA be included when completing the death certificate.
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Affiliation(s)
- Emily Molina
- University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.
| | - Inmaculada del Rincon
- University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.
| | - Jose Felix Restrepo
- University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.
| | | | - Agustin Escalante
- University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.
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Mantel Ä, Holmqvist M, Jernberg T, Wållberg-Jonsson S, Askling J. Rheumatoid arthritis is associated with a more severe presentation of acute coronary syndrome and worse short-term outcome. Eur Heart J 2015; 36:3413-22. [PMID: 26400826 DOI: 10.1093/eurheartj/ehv461] [Citation(s) in RCA: 81] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Accepted: 08/19/2015] [Indexed: 12/18/2022] Open
Abstract
AIMS Despite a wealth of studies describing an increased incidence of acute coronary syndromes (ACSs) in rheumatoid arthritis (RA), considerably less is known about the clinical characteristics and their association with short-term outcome of such ACS. The aims of this study were therefore to investigate clinical characteristics and case-fatality rates following ACS in patients with RA. METHODS AND RESULTS We compared the clinical presentation of incident ACS between 2007 and 2010 and their short-term mortality in a cohort of 1135 subjects with prevalent RA and in a cohort of 3184 matched general population comparators. Rheumatoid arthritis subjects more frequently presented with sudden cardiac death, ST-segment elevation myocardial infarctions, had higher levels of troponin and higher frequencies of in-hospital complications compared with the general population comparators. Furthermore, the short-term mortality was higher among RA-associated ACS (7-day hazard ratio (HR) = 1.65 [95% CI 1.32-2.08]; 30-day HR = 1.57 [95% CI 1.30-1.89]), which were somewhat attenuated but remained statistically significantly increased following adjustment for previous comorbidities, demographics, and educational level (7-day HR = 1.50 [95% CI 1.19-1.90]; 30-day HR = 1.43 [95% CI 1.18-1.72]), and for ACS type (7-day HR = 1.44 [95% CI 1.14-1.82]; 30-day HR = 1.36 [95% CI 1.13-1.64]). CONCLUSION Patients with prevalent RA suffer more severe ACSs compared with the general population and also have poorer outcomes after the events, which can only partly be explained by increased event severity.
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Affiliation(s)
- Ängla Mantel
- Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Solna, Stockholm SE-171 76, Sweden
| | - Marie Holmqvist
- Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Solna, Stockholm SE-171 76, Sweden
| | - Tomas Jernberg
- Section of Cardiology, Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden
| | | | - Johan Askling
- Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Solna, Stockholm SE-171 76, Sweden
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Giles JT. Cardiovascular disease in rheumatoid arthritis: Current perspectives on assessing and mitigating risk in clinical practice. Best Pract Res Clin Rheumatol 2015; 29:597-613. [DOI: 10.1016/j.berh.2015.09.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Nurmohamed M, Bao Y, Signorovitch J, Trahey A, Mulani P, Furst DE. Longer durations of antitumour necrosis factor treatment are associated with reduced risk of cardiovascular events in patients with rheumatoid arthritis. RMD Open 2015; 1:e000080. [PMID: 26535138 PMCID: PMC4612693 DOI: 10.1136/rmdopen-2015-000080] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 04/23/2015] [Accepted: 04/27/2015] [Indexed: 12/20/2022] Open
Abstract
Objective To assess the effects of treatment with antitumour necrosis factor (TNF) agents, methotrexate, or other non-biological disease-modifying antirheumatic drugs (DMARDs) on cardiovascular event risks among patients with rheumatoid arthritis (RA). Methods We conducted a retrospective study using data from the MarketScan claims database. Patients with RA with ≥1 prescription for an index drug were included. Each patient's use of an index drug was calculated cumulatively as a time-varying exposure. The incidence of cardiovascular events among patients with RA was determined. Associations between drug exposures and occurrence of cardiovascular events were assessed with Cox proportional hazards models. Results Of 113 677 patients identified, 35.8%, 41.1% and 23.1% received anti-TNF agents, methotrexate and other DMARDs, respectively. Patients were treated for an average of 7.6 months; 2138 patients (1.9%) had a cardiovascular event following their index prescription. Each additional 6 months of anti-TNF therapy use versus non-use reduced the risk (HR; 95% CI) for any cardiovascular event by 12% (0.88; 0.81 to 0.95, p=0.002). Anti-TNF therapy was associated with a 13% and 12% reduction in cardiovascular events in patients aged ≥50 years (0.87; 0.80 to 0.95, p=0.002) and in those without prior methotrexate use (0.88; 0.78 to 0.99, p=0.04), respectively. Cumulative use of 1, 2 or 3 years of anti-TNF therapy versus non-use is expected to reduce cardiovascular event risks by 21%, 38% and 51%, respectively. Conclusions Anti-TNF therapy was associated with a significantly lower risk of cardiovascular events among patients with RA, older patients with RA and patients without prior exposure to methotrexate.
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Affiliation(s)
- Michael Nurmohamed
- Departments of Internal Medicine and Rheumatology , VU University Medical Centre , Amsterdam , The Netherlands
| | - Yanjun Bao
- Health Economics and Outcomes Research, AbbVie , North Chicago, Illinois , USA
| | | | - Alex Trahey
- The Analysis Group , Boston, Massachusetts , USA
| | - Parvez Mulani
- Health Economics and Outcomes Research, AbbVie , North Chicago, Illinois , USA
| | - Daniel E Furst
- University of California-Los Angeles (UCLA) , Los Angeles, California , USA
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Rasch LA, Bultink IEM, van Tuyl LHD, Lems WF. Glucocorticoid safety for treating rheumatoid arthritis. Expert Opin Drug Saf 2015; 14:839-44. [PMID: 25802019 DOI: 10.1517/14740338.2015.1027681] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
INTRODUCTION Glucocorticoids (GCs) are often used in the treatment of rheumatoid arthritis and many other inflammatory diseases. Besides strong favorable effects on disease activity, GCs can cause (serious) side effects as well. AREAS COVERED Side effects of GCs that are ranked as most important by rheumatologists as well as by patients are bone loss and fractures, cardiovascular events, hypertension, and diabetes mellitus. In evaluating these side effects, confounding by indication is a disturbing factor: not only the use of GCs can increase the risk of several side effects, but so can the activity of the underlying disease, which in turn is related to the amount of GCs that is prescribed to the patient. EXPERT OPINION Generally, side effects predominantly occur in patients with a high disease activity and when used in high doses and for a long period of time. For these patients, caution and monitoring are most warranted. However, monitoring is not only recommended in patients with a high disease activity, and high-dose or long-term use of GCs, but in all GC users, since side effects may also occur in patients treated with low-dose GCs. When detecting possible negative effects in time, they might be managed and serious damage due to side effects might hopefully be prevented.
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Affiliation(s)
- Linda A Rasch
- VU University Medical Center, Department of Rheumatology , Room 3A54, PO Box 7057, 1007 MB Amsterdam , The Netherlands +31 (0) 20 444 2485 ; +31 (0) 20 444 2138 ;
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Zardi EM, Sambataro G, Basta F, Margiotta DPE, Afeltra AMV. Subclinical carotid atherosclerosis in elderly patients with primary Sjögren syndrome: a duplex Doppler sonographic study. Int J Immunopathol Pharmacol 2015; 27:645-51. [PMID: 25572746 DOI: 10.1177/039463201402700422] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
A growing body of evidence presents a link between chronic inflammatory rheumatic diseases and atherosclerosis. To evaluate subclinical carotid atherosclerosis in an elderly group of patients with primary Sjögren syndrome compared with a control group matched for age, sex, ethnicity and cardiovascular risk factors, we enrolled 18 patients with Primary Sjögren Syndrome (mean age 65 ± 5.93 SD) and 18 mild Ostheoarthritic patients (mean age 66 ± 5.94 SD) from the outpatient department of Rheumatology, University Campus Bio-Medico, Rome, Italy, matched for age, sex, ethnicity and cardiovascular risk factors. A duplex Doppler sonographic study of carotids was performed in order to evaluate intima-media thickness (IMT), stiffness and haemodynamic parameters [resistivity and pulsatility indices (RI and PI, respectively)]. No significant difference was found between primary Sjögren syndrome and control patients in IMT, stiffness and haemodynamic parameters. The lack of significant difference in subclinical atherosclerosis between elderly primary Sjögren syndrome and control matched patients, indicates that traditional cardiovascular risk factors, immunologic alterations and chronic inflammation do not influence the progression of vascular damage in the carotid circulation of patients with median disease duration of 6.5 years.
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Affiliation(s)
- E M Zardi
- Department of Clinical Medicine and Rheumatology, University Campus Bio-Medico of Rome, Rome, Italy
| | - G Sambataro
- Department of Clinical Medicine and Rheumatology, University Campus Bio-Medico of Rome, Rome, Italy
| | - F Basta
- Department of Clinical Medicine and Rheumatology, University Campus Bio-Medico of Rome, Rome, Italy
| | - D P E Margiotta
- Department of Clinical Medicine and Rheumatology, University Campus Bio-Medico of Rome, Rome, Italy
| | - A M V Afeltra
- Department of Clinical Medicine and Rheumatology, University Campus Bio-Medico of Rome, Rome, Italy
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Santiago T, da Silva JAP. Safety of glucocorticoids in rheumatoid arthritis: evidence from recent clinical trials. Neuroimmunomodulation 2015; 22:57-65. [PMID: 25228045 DOI: 10.1159/000362726] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Glucocorticoids are one of the most effective treatments for rheumatoid arthritis, with well-established efficacy in controlling the disease symptoms and structural progression. Fears regarding their toxicity are reflected in common recommendations for the use of the lowest possible dose for the shortest possible time. We herein review toxicity data obtained in randomized clinical trials of low-dose glucocorticoid in rheumatoid arthritis, given that observational studies cannot guarantee the avoidance of bias by indication. Seven eligible randomized controlled trials were identified. These publications do not identify any strong signal of relevant toxicity of glucocorticoid in doses of up to 10 mg of prednisone equivalent/day for up to 2 years. However, the quantity (1,100 patient years of exposure) and especially the quality of evidence are too limited to establish conclusions. A large prospective trial dedicated to the toxicity of low-dose glucocorticoid is dearly needed. Meanwhile, adherence to recommendations on standardized methodologies for the registration and report of glucocorticoid adverse events is essential to improve our knowledge and competence in the best management of these important medications.
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Affiliation(s)
- Tânia Santiago
- Rheumatology Unit, Centro Hospitalar e Universistário de Coimbra, Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal
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Hwang YG, Saag K. The safety of low-dose glucocorticoids in rheumatic diseases: results from observational studies. Neuroimmunomodulation 2015; 22:72-82. [PMID: 25228230 DOI: 10.1159/000362727] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Glucocorticoids (GC) remain the most commonly used agents for managing inflammatory rheumatic diseases. The adverse effects (AEs) associated with high-dose GCs are well established, but there is a widespread misconception that AEs of high-dose GC therapy (>30 mg of prednisone or equivalent daily) are similar in low-dose therapy (≤7.5 mg of prednisone equivalent a day). Although high-quality evidence on AEs of low-dose GC therapy is still incomplete, risks and safety of low-dose GC therapy in rheumatic diseases are reviewed based on current evidence by category, including musculoskeletal, cardiovascular, infectious, gastrointestinal, neuropsychiatric, endocrine and metabolic, dermatologic, and ophthalmologic AEs. Recommendations concerning monitoring AEs with low-dose GC therapy are provided for each category of AEs on the basis of our literature review and clinical experience. There is emerging evidence that low-dose GCs are associated with a much lower level of AEs, which would allow their use over long periods in patients with rheumatic disease who gain clinical effectiveness and well-being from their use. Nonetheless, knowledge and understanding of AEs from low-dose GCs is vital to maximize benefits and minimize risks to patients.
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Affiliation(s)
- Yong Gil Hwang
- Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pa., USA
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