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Kaleta K, Krupa J, Suchy W, Sopel A, Korkosz M, Nowakowski J. Endothelial dysfunction and risk factors for atherosclerosis in psoriatic arthritis: overview and comparison with rheumatoid arthritis. Rheumatol Int 2024; 44:1587-1606. [PMID: 38522049 PMCID: PMC11343792 DOI: 10.1007/s00296-024-05556-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Accepted: 02/05/2024] [Indexed: 03/25/2024]
Abstract
Endothelial dysfunction (ED) is defined as an impairment in the vasodilatory, anti-thrombotic, and anti-inflammatory properties of the cells that make up the lining of blood vessels. ED is considered a key step in the development of atherosclerotic cardiovascular disease. The association between ED and systemic inflammatory diseases is well established. However, the prevalence and clinical significance of ED in psoriatic arthritis (PsA) have been investigated to a lesser extent. This review aims to explore the link between ED and PsA, including ED in macro- and microcirculation, as well as risk factors for its occurrence in PsA and its relationship with atherosclerosis in PsA. Furthermore, the ED in PsA was compared with that of rheumatoid arthritis (RA). Regarding ED in the microcirculation, the coronary flow reserve was found to be significantly reduced in individuals with PsA. The relationship between PsA and macrovascular ED is more pronounced, along with more advanced atherosclerosis detected in patients with PsA. These results are consistent with those obtained in RA studies. On the other hand, arterial stiffness and signs of vascular remodeling were found more frequently in RA than in PsA, with the potential role of efficient anti-TNF treatment in patients with PsA and psoriasis explaining this finding. The impact of ED on cardiovascular diseases and the burden of this risk caused independently by PsA have not yet been precisely established, however, this group of patients requires special attention with regard to cardiovascular events.
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Affiliation(s)
- Konrad Kaleta
- Students' Scientific Group at the Department of Rheumatology and Immunology, Jagiellonian University Medical College, Kraków, Poland
| | - Julia Krupa
- Students' Scientific Group at the Department of Rheumatology and Immunology, Jagiellonian University Medical College, Kraków, Poland
| | - Wiktoria Suchy
- Students' Scientific Group at the Department of Rheumatology and Immunology, Jagiellonian University Medical College, Kraków, Poland
| | - Anna Sopel
- Students' Scientific Group at the Department of Rheumatology and Immunology, Jagiellonian University Medical College, Kraków, Poland
| | - Mariusz Korkosz
- Department of Rheumatology and Immunology, Jagiellonian University Medical College, Kraków, Poland
| | - Jarosław Nowakowski
- Department of Rheumatology and Immunology, Jagiellonian University Medical College, Kraków, Poland.
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El Hawary MS, Hassan SA, ELatty SA, Khalil NM. Anti-Carbamylated Protein Antibodies, Tumour Necrosis Factor Alpha and Insulin Resistance in Egyptian Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus. REUMATOLOGIA CLINICA 2022; 18:469-474. [PMID: 36210141 DOI: 10.1016/j.reumae.2022.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Accepted: 05/19/2021] [Indexed: 06/16/2023]
Abstract
BACKGROUND Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are autoimmune diseases. Premature atherosclerosis and cardiovascular diseases are two of the most important complications of these diseases. Anti-carbamylated protein antibody (Anti-carP Ab) is one of the antibodies which was studied in RA and SLE. In our study, we studied the relation between anti-carP Ab, disease activity and insulin resistance in RA and SLE patients. METHODS 90Patients with SLE and RA were enrolled and subjected to history taking, clinical examination and assessment of disease activity using SLE disease activity index 2000 (SLEDAI-2K) scoring for SLE patients and disease activity score 28 (DAS28-ESR) for RA patients. Samples were examined for complete blood count (CBC), creatinine, inflammatory markers, Tumour necrosis factor alpha (TNF alpha), fasting insulin, fasting blood sugar (FBS), lipid profile and anti-carPAb. HOMA-IR (homeostasis model assessment for insulin resistance) was calculated. RESULTS Patients with RA and SLE showed higher levels of anti-carPAb in comparison with healthy subjects (8.25ng/ml for RA, 7ng/ml for SLE and 0.6ng/ml for healthy subjects with p value <0.001). There was a positive correlation between anti-carPAb and disease activity of RA (p value <0.001) and a positive correlation between anti-carPAb and TNF alpha in RA. In SLE, there was no correlation of anti-carP Ab with disease activity while, HOMA-IR showed a positive correlation with nephritis (p value 0.04). CONCLUSION Anti-carP antibody is a marker of disease activity in RA patients and has high specificity for both RA and SLE detection.
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Affiliation(s)
| | - Sarah A Hassan
- Internal Medicine Department, Faculty of Medicine, Cairo University, Egypt
| | - Sahar Abd ELatty
- Chemical Pathology Department, Faculty of Medicine, Cairo University, Egypt
| | - Noha M Khalil
- Internal Medicine Department, Faculty of Medicine, Cairo University, Egypt.
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Infante M, Padilla N, Alejandro R, Caprio M, Della-Morte D, Fabbri A, Ricordi C. Diabetes-Modifying Antirheumatic Drugs: The Roles of DMARDs as Glucose-Lowering Agents. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:571. [PMID: 35629988 PMCID: PMC9143119 DOI: 10.3390/medicina58050571] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 04/14/2022] [Accepted: 04/18/2022] [Indexed: 02/06/2023]
Abstract
Systemic inflammation represents a shared pathophysiological mechanism which underlies the frequent clinical associations among chronic inflammatory rheumatic diseases (CIRDs), insulin resistance, type 2 diabetes (T2D), and chronic diabetes complications, including cardiovascular disease. Therefore, targeted anti-inflammatory therapies are attractive and highly desirable interventions to concomitantly reduce rheumatic disease activity and to improve glucose control in patients with CIRDs and comorbid T2D. Therapeutic approaches targeting inflammation may also play a role in the prevention of prediabetes and diabetes in patients with CIRDs, particularly in those with traditional risk factors and/or on high-dose corticosteroid therapy. Recently, several studies have shown that different disease-modifying antirheumatic drugs (DMARDs) used for the treatment of CIRDs exert antihyperglycemic properties by virtue of their anti-inflammatory, insulin-sensitizing, and/or insulinotropic effects. In this view, DMARDs are promising drug candidates that may potentially reduce rheumatic disease activity, ameliorate glucose control, and at the same time, prevent the development of diabetes-associated cardiovascular complications and metabolic dysfunctions. In light of their substantial antidiabetic actions, some DMARDs (such as hydroxychloroquine and anakinra) could be alternatively termed "diabetes-modifying antirheumatic drugs", since they may be repurposed for co-treatment of rheumatic diseases and comorbid T2D. However, there is a need for future randomized controlled trials to confirm the beneficial metabolic and cardiovascular effects as well as the safety profile of distinct DMARDs in the long term. This narrative review aims to discuss the current knowledge about the mechanisms behind the antihyperglycemic properties exerted by a variety of DMARDs (including synthetic and biologic DMARDs) and the potential use of these agents as antidiabetic medications in clinical settings.
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Affiliation(s)
- Marco Infante
- Clinical Cell Transplant Program (CCTP), Diabetes Research Institute, University of Miami Miller School of Medicine, 1450 NW 10th Ave, Miami, FL 33136, USA; (R.A.); (C.R.)
- Department of Systems Medicine, Diabetes Research Institute Federation (DRIF), University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy;
- Section of Endocrinology, UniCamillus, Saint Camillus International University of Health Sciences, Via di Sant’Alessandro 8, 00131 Rome, Italy
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Via Cola di Rienzo 28, 00192 Rome, Italy
| | - Nathalia Padilla
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Colonia Centroamérica L-823, Managua 14048, Nicaragua;
| | - Rodolfo Alejandro
- Clinical Cell Transplant Program (CCTP), Diabetes Research Institute, University of Miami Miller School of Medicine, 1450 NW 10th Ave, Miami, FL 33136, USA; (R.A.); (C.R.)
| | - Massimiliano Caprio
- Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele Roma, Via di Val Cannuta 247, 00166 Rome, Italy;
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, Via di Val Cannuta 247, 00166 Rome, Italy;
| | - David Della-Morte
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, Via di Val Cannuta 247, 00166 Rome, Italy;
- Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
- Department of Neurology, Evelyn F. McKnight Brain Institute, University of Miami Miller School of Medicine, 1120 NW 14th St., Miami, FL 33136, USA
| | - Andrea Fabbri
- Department of Systems Medicine, Diabetes Research Institute Federation (DRIF), University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy;
| | - Camillo Ricordi
- Clinical Cell Transplant Program (CCTP), Diabetes Research Institute, University of Miami Miller School of Medicine, 1450 NW 10th Ave, Miami, FL 33136, USA; (R.A.); (C.R.)
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Cai W, Tang X, Pang M. Prevalence of Metabolic Syndrome in Patients With Rheumatoid Arthritis: An Updated Systematic Review and Meta-Analysis. Front Med (Lausanne) 2022; 9:855141. [PMID: 35462993 PMCID: PMC9024100 DOI: 10.3389/fmed.2022.855141] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 03/03/2022] [Indexed: 12/12/2022] Open
Abstract
Introduction Rheumatoid arthritis (RA) due to systemic inflammation and insulin resistance increases the risk of cardiovascular disease and reduces life expectancy. In order to develop cardiac death prevention strategies, it is necessary to estimate the prevalence of metabolic syndrome (MetS) in these patients. Methods This systematic review and meta-analysis was performed to estimate the prevalence of MetS among patients with RA. International databases (i.e., Scopus, PubMed, Web of Science, and Google Scholar) were searched during the period of October 1 and October 10, 20121. Heterogeneity among the included studies was assessed through the Cochrane Q test statistics and I2 test. Finally, a random-effects meta-analysis model was computed to estimate the pooled prevalence of MetS. Results Sixty-one articles with 96 groups and a sample size of 13,644 people were analyzed. The pooled prevalence of MetS was 32% (95% CI: 29.6–34.4). The highest prevalence of MetS is related to studies conducted in Asia (32.7%, 95% CI: 29–36.3) and Europe (32.7%, 95% CI: 27.5.37.9) and the lowest Prevalence was also related to studies conducted in Africa (28%, 95% CI: 28.8–32.2). The prevalence of MetS in men was 33% (95% CI: 26–39) and 34% (95% CI: 29–40) in women. Findings by diagnostic criteria showed that the highest and lowest prevalence of MetS was related to ATP III (37.5%, 95% CI: 30.9–44.2) and EGIR (14.4%, 95% CI: 10.5–18.5), respectively. Conclusions MetS is highly prevalent in patients with RA and identification of high-risk patients is necessary to prevent cardiovascular mortality.
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Affiliation(s)
- Wei Cai
- Pediatric Department, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China
- *Correspondence: Wei Cai
| | - Xuemi Tang
- Department of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Min Pang
- Department of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China
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Mena-Vázquez N, Redondo-Rodríguez R, Rioja J, Jimenez-Nuñez FG, Manrique-Arija S, Lisbona-Montañez JM, Cano-García L, Rojas-Gimenez M, Ureña I, Valdivielso P, Fernández-Nebro A. Postprandial Hyperlipidemia: Association with Inflammation and Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis. Biomedicines 2022; 10:133. [PMID: 35052812 PMCID: PMC8773280 DOI: 10.3390/biomedicines10010133] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 12/30/2021] [Accepted: 01/06/2022] [Indexed: 12/10/2022] Open
Abstract
OBJECTIVE To describe postprandial lipidemia in patients with rheumatoid arthritis (RA) and to analyze its association with subclinical atherosclerosis and inflammatory activity. METHODS Observational study of 80 cases of RA and 80 sex- and age-matched controls. We excluded individuals with dyslipidemia. Postprandial hyperlipidemia (PPHL) was defined as postprandial triglycerides >220 mg/dL and/or postprandial ApoB48 levels >75th percentile (>p75). Plasma lipids, cholesterol, triglycerides, ApoB48, and total ApoB were evaluated at baseline and after a meal. Other variables analyzed included subclinical atherosclerosis (defined as presence of carotid atheromatous plaque), inflammatory activity (disease activity score (DAS28-ESR)), cytokines, apolipoproteins, and physical activity. A multivariate analysis was performed to identify factors associated with PPHL in patients with RA. RESULTS A total of 75 patients with RA and 67 healthy controls fulfilled the inclusion criteria. PPHL was more frequent in patients with RA than controls (No. (%), 29 (38.70) vs. 15 (22.40); p = 0.036), as was subclinical atherosclerosis (No. (%), 22 (30.10) vs. 10 (14.90); p = 0.032). PPHL in patients with RA was associated with subclinical atherosclerosis (OR (95% CI) 4.69 (1.09-12.11); p = 0.037), TNF-α (OR (95% CI) 2.00 (1.00-3.98); p = 0.048), high-sensitivity C-reactive protein (OR (95% CI) 1.10 (1.01-1.19); p = 0.027), and baseline triglycerides (OR (95% CI) 1.02 (1.00-1.04); p = 0.049). CONCLUSION PPHL was more frequent in patients with RA than in controls. PPHL in patients with RA was associated with inflammation and subclinical atherosclerosis.
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Affiliation(s)
- Natalia Mena-Vázquez
- Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain; (R.R.-R.); (J.R.); (F.G.J.-N.); (S.M.-A.); (L.C.-G.); (I.U.); (P.V.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Malaga, Spain;
- Departamento de Medicina y Dermatología, Universidad de Málaga, 29010 Malaga, Spain
| | - Rocío Redondo-Rodríguez
- Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain; (R.R.-R.); (J.R.); (F.G.J.-N.); (S.M.-A.); (L.C.-G.); (I.U.); (P.V.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Malaga, Spain;
| | - José Rioja
- Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain; (R.R.-R.); (J.R.); (F.G.J.-N.); (S.M.-A.); (L.C.-G.); (I.U.); (P.V.); (A.F.-N.)
- Departamento de Medicina y Dermatología, Universidad de Málaga, 29010 Malaga, Spain
| | - Francisco Gabriel Jimenez-Nuñez
- Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain; (R.R.-R.); (J.R.); (F.G.J.-N.); (S.M.-A.); (L.C.-G.); (I.U.); (P.V.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Malaga, Spain;
| | - Sara Manrique-Arija
- Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain; (R.R.-R.); (J.R.); (F.G.J.-N.); (S.M.-A.); (L.C.-G.); (I.U.); (P.V.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Malaga, Spain;
- Departamento de Medicina y Dermatología, Universidad de Málaga, 29010 Malaga, Spain
| | - Jose Manuel Lisbona-Montañez
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Malaga, Spain;
- Departamento de Medicina y Dermatología, Universidad de Málaga, 29010 Malaga, Spain
| | - Laura Cano-García
- Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain; (R.R.-R.); (J.R.); (F.G.J.-N.); (S.M.-A.); (L.C.-G.); (I.U.); (P.V.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Malaga, Spain;
| | - Marta Rojas-Gimenez
- UGC de Reumatología, Instituto Maimónides de Investigación Biomédica de Cordoba (IMIBIC), Hospital Universitario Reina Sofia, 14004 Cordoba, Spain;
| | - Inmaculada Ureña
- Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain; (R.R.-R.); (J.R.); (F.G.J.-N.); (S.M.-A.); (L.C.-G.); (I.U.); (P.V.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Malaga, Spain;
| | - Pedro Valdivielso
- Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain; (R.R.-R.); (J.R.); (F.G.J.-N.); (S.M.-A.); (L.C.-G.); (I.U.); (P.V.); (A.F.-N.)
- Departamento de Medicina y Dermatología, Universidad de Málaga, 29010 Malaga, Spain
- UGC de Medicina Interna, Hospital Universitario Virgen de la Victoria, 29010 Malaga, Spain
| | - Antonio Fernández-Nebro
- Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain; (R.R.-R.); (J.R.); (F.G.J.-N.); (S.M.-A.); (L.C.-G.); (I.U.); (P.V.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Malaga, Spain;
- Departamento de Medicina y Dermatología, Universidad de Málaga, 29010 Malaga, Spain
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Rouached L, Tekaya R, Ahmed H, Tekaya A, Bouzid K, Bouden S, Saidane O, Mahmoud I, Abdelmoula L. Prevalence of metabolic syndrome in rheumatoid arthritis patients: Association with disease. INDIAN JOURNAL OF RHEUMATOLOGY 2022. [DOI: 10.4103/injr.injr_122_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Rojas-Giménez M, López-Medina C, Calvo-Gutiérrez J, Puche-Larrubia MÁ, Gómez-García I, Seguí-Azpilcueta P, Ábalos-Aguilera MDC, Ruíz D, Collantes-Estévez E, Escudero-Contreras A. Association between Carotid Intima-Media Thickness and the Use of Biological or Small Molecule Therapies in Patients with Rheumatoid Arthritis. Diagnostics (Basel) 2021; 12:diagnostics12010064. [PMID: 35054229 PMCID: PMC8775122 DOI: 10.3390/diagnostics12010064] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/23/2021] [Accepted: 12/27/2021] [Indexed: 11/16/2022] Open
Abstract
Objective: The objective of this study was to assess the association of carotid intima-media thickness (CIMT), and also the presence of atheromatous plaque, with biological and targeted synthetic disease-modifying antirheumatic drugs, in an established cohort of patients with rheumatoid arthritis (RA). Patients and Methods: We conducted a cross-sectional observational study based on a cohort of patients with RA and a registry of healthy controls, in whom the CIMT and presence of atheromatous plaque were assessed by ultrasound. Data were collected on disease activity, lab results and treatments. Descriptive and bivariate analyses were performed and two multivariate linear regression models (with CIMT as the dependent variable) were constructed to identify variables independently associated with CIMT in our sample of patients with RA. Results: A total of 176 individuals (146 patients with RA and 30 controls) were included. A higher percentage of patients than controls had atheromatous plaque (33.8% vs. 12.5%, p = 0.036), but no differences were found in terms of CIMT (0.64 vs. 0.61, p = 0.444). Compared to values in patients on other therapies, the CIMT was smaller among patients on tumour necrosis factor alpha (TNFα) inhibitors (mean [SD]: 0.58 [0.10] vs. 0.65 [0.19]; p = 0.013) and among those on Janus kinase inhibitors (mean [SD]: 0.52 [0.02] vs. 0.64 [0.18]; p < 0.001), while no differences were found as a function of the use of the other therapies considered. The multivariate linear regression analysis to identify factors associated with CIMT in our patients, adjusting for traditional cardiovascular risk factors such as hypertension, high levels of low-density lipoproteins, diabetes mellitus and smoking, showed that male sex, older age and having a greater cumulative erythrocyte sedimentation rate were independently associated with a larger CIMT, while patients on TNFα inhibitors had a CIMT 0.075 mm smaller than those on other treatments. Conclusions: The use of TNFα inhibitors may protect against subclinical atherosclerosis in patients with RA, patients on this biologic having smaller CIMTs than patients on other disease-modifying antirheumatic drugs. Nonetheless, these results should be confirmed in prospective studies with larger sample sizes.
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Affiliation(s)
- Marta Rojas-Giménez
- Rheumatology Department, Reina Sofía University Hospital, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), University of Córdoba (UCO), 14004 Cordoba, Spain; (M.R.-G.); (J.C.-G.); (M.Á.P.-L.); (I.G.-G.); (D.R.)
| | - Clementina López-Medina
- Rheumatology Department, Reina Sofía University Hospital, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), University of Córdoba (UCO), 14004 Cordoba, Spain; (M.R.-G.); (J.C.-G.); (M.Á.P.-L.); (I.G.-G.); (D.R.)
- Correspondence:
| | - Jerusalem Calvo-Gutiérrez
- Rheumatology Department, Reina Sofía University Hospital, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), University of Córdoba (UCO), 14004 Cordoba, Spain; (M.R.-G.); (J.C.-G.); (M.Á.P.-L.); (I.G.-G.); (D.R.)
| | - María Ángeles Puche-Larrubia
- Rheumatology Department, Reina Sofía University Hospital, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), University of Córdoba (UCO), 14004 Cordoba, Spain; (M.R.-G.); (J.C.-G.); (M.Á.P.-L.); (I.G.-G.); (D.R.)
| | - Ignacio Gómez-García
- Rheumatology Department, Reina Sofía University Hospital, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), University of Córdoba (UCO), 14004 Cordoba, Spain; (M.R.-G.); (J.C.-G.); (M.Á.P.-L.); (I.G.-G.); (D.R.)
| | - Pedro Seguí-Azpilcueta
- Reina Sofia University Hospital, Maimonides Research Institute of Biomedical Medicine from Cordoba (IMIBIC), University of Córdoba, 14004 Cordoba, Spain; (P.S.-A.); (M.d.C.Á.-A.); (E.C.-E.); (A.E.-C.)
| | - María del Carmen Ábalos-Aguilera
- Reina Sofia University Hospital, Maimonides Research Institute of Biomedical Medicine from Cordoba (IMIBIC), University of Córdoba, 14004 Cordoba, Spain; (P.S.-A.); (M.d.C.Á.-A.); (E.C.-E.); (A.E.-C.)
| | - Desirée Ruíz
- Rheumatology Department, Reina Sofía University Hospital, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), University of Córdoba (UCO), 14004 Cordoba, Spain; (M.R.-G.); (J.C.-G.); (M.Á.P.-L.); (I.G.-G.); (D.R.)
| | - Eduardo Collantes-Estévez
- Reina Sofia University Hospital, Maimonides Research Institute of Biomedical Medicine from Cordoba (IMIBIC), University of Córdoba, 14004 Cordoba, Spain; (P.S.-A.); (M.d.C.Á.-A.); (E.C.-E.); (A.E.-C.)
| | - Alejandro Escudero-Contreras
- Reina Sofia University Hospital, Maimonides Research Institute of Biomedical Medicine from Cordoba (IMIBIC), University of Córdoba, 14004 Cordoba, Spain; (P.S.-A.); (M.d.C.Á.-A.); (E.C.-E.); (A.E.-C.)
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Autoimmune Rheumatic Diseases and Vascular Function: The Concept of Autoimmune Atherosclerosis. J Clin Med 2021; 10:jcm10194427. [PMID: 34640445 PMCID: PMC8509415 DOI: 10.3390/jcm10194427] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 09/20/2021] [Accepted: 09/22/2021] [Indexed: 12/18/2022] Open
Abstract
Autoimmune rheumatic diseases (AIRDs) with unknown etiology are increasing in incidence and prevalence. Up to 5% of the population is affected. AIRDs include rheumatoid arthritis, system lupus erythematosus, systemic sclerosis, and Sjögren's syndrome. In patients with autoimmune diseases, the immune system attacks structures of its own body, leading to widespread tissue and organ damage, which, in turn, is associated with increased morbidity and mortality. One third of the mortality associated with autoimmune diseases is due to cardiovascular diseases. Atherosclerosis is considered the main underlying cause of cardiovascular diseases. Currently, because of finding macrophages and lymphocytes at the atheroma, atherosclerosis is considered a chronic immune-inflammatory disease. In active inflammation, the liberation of inflammatory mediators such as tumor necrotic factor alpha (TNFa), interleukine-6 (IL-6), IL-1 and other factors like T and B cells, play a major role in the atheroma formation. In addition, antioxidized, low-density lipoprotein (LDL) antibodies, antinuclear antibodies (ANA), and rheumatoid factor (RF) are higher in the atherosclerotic patients. Traditional risk factors like gender, age, hypercholesterolemia, smoking, diabetes mellitus, and hypertension, however, do not alone explain the risk of atherosclerosis present in autoimmune diseases. This review examines the role of chronic inflammation in the etiology-and progression-of atherosclerosis in autoimmune rheumatic diseases. In addition, discussed here in detail are the possible effects of autoimmune rheumatic diseases that can affect vascular function. We present here the current findings from studies that assessed vascular function changes using state-of-the-art techniques and innovative endothelial function biomarkers.
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A Pilot Study: Hypertension, Endothelial Dysfunction and Retinal Microvasculature in Rheumatic Autoimmune Diseases. J Clin Med 2021; 10:jcm10184067. [PMID: 34575178 PMCID: PMC8467719 DOI: 10.3390/jcm10184067] [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: 07/17/2021] [Revised: 08/26/2021] [Accepted: 09/07/2021] [Indexed: 12/14/2022] Open
Abstract
Background: The etiology of autoimmune rheumatic diseases is unknown. Endothelial dysfunction and premature atherosclerosis are commonly seen in these patients. Atherosclerosis is considered one of the main causes of cardiovascular diseases. Hypertension is considered the most important traditional cardiovascular risk. This case-control study aimed to investigate the relationship between autoimmune diseases and cardiovascular risk. Methods: This study was carried out in patients with rheumatoid arthritis, RA (n = 10), primary Sjögren syndrome, PSS (n = 10), and healthy controls (n = 10). Mean blood pressure (MBP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse wave velocity (PWV, an indicator of arterial stiffness) were assessed via a Vicorder device. Asymmetric dimethylarginine (ADMA) was measured via ELISA. Retinal photos were taken via a CR-2 retinal camera, and retinal microvasculature analysis was carried out. T-tests were conducted to compare the disease and control groups. ANOVA and ANOVA—ANCOVA were also used for the correction of covariates. Results: A high prevalence of hypertension was seen in RA (80% of cases) and PSS (40% of cases) compared to controls (only 20% of cases). Significant changes were seen in MBP (RA 101 ± 11 mmHg; PSS 93 ± 10 mm Hg vs. controls 88 ± 7 mmHg, p = 0.010), SBP (148 ± 16 mmHg in RA vs. 135 ± 16 mmHg in PSS vs. 128 ± 11 mmHg in control group; p = 0.007), DBP (77 ± 8 mmHg in RA, 72 ± 8 mmHg in PSS vs. 67 ± 6 mmHg in control; p = 0.010 in RA compared to the controls). Patients with PSS showed no significant difference as compared to controls (MBP: p = 0.240, SBP: p = 0.340, DBP: p = 0.190). Increased plasma ADMA was seen in RA (0.45 ± 0.069 ng/mL) and PSS (0.43 ± 0.060 ng/mL) patients as compared to controls (0.38 ± 0.059 ng/mL). ADMA in RA vs. control was statistically significant (p = 0.022). However, no differences were seen in ADMA in PSS vs. controls. PWV and retinal microvasculature did not differ across the three groups. Conclusions: The prevalence of hypertension in our cohort was very high. Similarly, signs of endothelial dysfunction were seen in autoimmune rheumatic diseases. As hypertension and endothelial dysfunction are important contributing risk factors for cardiovascular diseases, the association of hypertension and endothelial dysfunction should be monitored closely in autoimmune diseases.
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El Hawary MS, Hassan SA, ELatty SA, Khalil NM. Anti-Carbamylated Protein Antibodies, Tumour Necrosis Factor Alpha and Insulin Resistance in Egyptian Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus. REUMATOLOGIA CLINICA 2021; 18:S1699-258X(21)00156-X. [PMID: 34266801 DOI: 10.1016/j.reuma.2021.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Revised: 04/16/2021] [Accepted: 05/19/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are autoimmune diseases. Premature atherosclerosis and cardiovascular diseases are two of the most important complications of these diseases. Anti-carbamylated protein antibody (Anti-carP Ab) is one of the antibodies which was studied in RA and SLE. In our study, we studied the relation between anti-carP Ab, disease activity and insulin resistance in RA and SLE patients. METHODS 90Patients with SLE and RA were enrolled and subjected to history taking, clinical examination and assessment of disease activity using SLE disease activity index 2000 (SLEDAI-2K) scoring for SLE patients and disease activity score 28 (DAS28-ESR) for RA patients. Samples were examined for complete blood count (CBC), creatinine, inflammatory markers, Tumour necrosis factor alpha (TNF alpha), fasting insulin, fasting blood sugar (FBS), lipid profile and anti-carPAb. HOMA-IR (homeostasis model assessment for insulin resistance) was calculated. RESULTS Patients with RA and SLE showed higher levels of anti-carPAb in comparison with healthy subjects (8.25ng/ml for RA, 7ng/ml for SLE and 0.6ng/ml for healthy subjects with p value <0.001). There was a positive correlation between anti-carPAb and disease activity of RA (p value <0.001) and a positive correlation between anti-carPAb and TNF alpha in RA. In SLE, there was no correlation of anti-carP Ab with disease activity while, HOMA-IR showed a positive correlation with nephritis (p value 0.04). CONCLUSION Anti-carP antibody is a marker of disease activity in RA patients and has high specificity for both RA and SLE detection.
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Affiliation(s)
| | - Sarah A Hassan
- Internal Medicine Department, Faculty of Medicine, Cairo University, Egypt
| | - Sahar Abd ELatty
- Chemical Pathology Department, Faculty of Medicine, Cairo University, Egypt
| | - Noha M Khalil
- Internal Medicine Department, Faculty of Medicine, Cairo University, Egypt.
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Wang Q, Zhang M, Wang M, Tai Y, Tao J, Zhou W, Han Y, Wei Wei. Triggers of Cardiovascular Diseases in Rheumatoid Arthritis. Curr Probl Cardiol 2021; 47:100853. [PMID: 34016483 DOI: 10.1016/j.cpcardiol.2021.100853] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 03/27/2021] [Indexed: 11/26/2022]
Abstract
The risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) is higher than that in patients without RA, and it is even higher than that in patients with diabetes. Autoimmune-mediated inflammation is observed in patients with RA, resulting in endothelial dysfunction, oxidative stress and activation, and vascular migration of white blood cells. Traditionally, RA-associated CVD was assumed to be mediated by disease-related inflammation, resulting in atherosclerosis (AS). However, this concept has been challenged because treatment with anti-rheumatic drugs, such as methotrexate or proinflammatory cytokine antagonists, such as tumor necrosis factor-alpha (TNF-α) inhibitors, did not reduce the risk of CVD in patients with RA. Current cardiovascular guidelines recommend screening and treatment of CVD risk factors in patients with RA but without clear biomarkers and treatment goals. There is no scientific basis for establishing therapeutic targets for cardiovascular risk factors in RA. Numerous studies have shown that the mechanism of early cardiac dysfunction in patients with RA may occur prior to AS. Therefore, it is crucial to explore the related mechanisms to prevent early cardiac dysfunction in patients with RA.
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Affiliation(s)
- Qingtong Wang
- Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China.
| | - Mei Zhang
- Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China
| | - Manman Wang
- Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China
| | - Yu Tai
- Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China
| | - Juan Tao
- Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China
| | - Weijie Zhou
- Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China
| | - Yongsheng Han
- Department of Emergency Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Wei Wei
- Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China.
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Manrique-Arija S, Mena-Vazquez N, Ureña I, Rioja J, Valdivielso P, Ginel-Mendoza L, Abad-Sánchez S, Jiménez-Núñez FG, Oliver-Martos B, Fernandez-Nebro A. Cumulative inflammatory burden and obesity as determinants of insulin resistance in patients with established rheumatoid arthritis: cross-sectional study. BMJ Open 2021; 11:e044749. [PMID: 33563625 PMCID: PMC7875272 DOI: 10.1136/bmjopen-2020-044749] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 12/29/2020] [Accepted: 01/13/2021] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVES To describe the prevalence of insulin resistance (IR) in patients with established rheumatoid arthritis (RA) and to analyse the contribution of cumulative inflammatory burden and other factors to its development. DESIGN Observational cross-sectional study. PARTICIPANTS Patients with RA and controls matched for age, sex and Body Mass Index. We excluded patients with diabetes. SETTINGS Patients from an RA inception cohort at Hospital Regional Universitario de Málaga, Spain, were recruited between September 2016 and May 2018. PRIMARY AND SECONDARY OUTCOME MEASURES IR was evaluated using the homeostasis model assessment for IR and beta-cell function and the quantitative insulin sensitivity check index. Other variables included the cumulative 28-Joint Disease Activity Score (DAS28) with C reactive protein (CRP) body composition and cytokines. Two logistic regression models were constructed to identify factors associated with IR in patients with RA. RESULTS Eighty-nine patients with RA and 80 controls were included. The prevalence of IR was similar in both cases and controls. Inflammatory activity was controlled appropriately in patients during follow-up (mean DAS28 3.1 (0.8)). The presence of IR in patients with RA was associated with obesity (OR 6.01, 95% CI 1.9 to 8.7), higher cumulative DAS28-CRP values during follow-up (OR 2.8, 95% CI 1.3 to 6.0), and higher interleukin-1β levels (OR 1.6, 95% CI 1.1 to 2.4). The second model showed that the risk of IR increased by 10% for each kilogram of excess body fat. CONCLUSION In patients with well-controlled, established RA, IR is associated mainly with poorer control of inflammation from diagnosis and with obesity, specifically total fat mass.
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Affiliation(s)
- Sara Manrique-Arija
- UGC de Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Natalia Mena-Vazquez
- UGC de Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Inmaculada Ureña
- UGC de Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain
| | - José Rioja
- Departamento de Medicina y Dermatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain
| | - Pedro Valdivielso
- UGC de Medicina Interna, Instituto de InvestigaciónBiomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain
| | | | - Salomé Abad-Sánchez
- Centro de Salud Ciudad Jardín, Distrito Sanitario Málaga-Guadalhorce, Málaga, Spain
| | - Francisco G Jiménez-Núñez
- UGC de Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Begoña Oliver-Martos
- UGC Neurociencias, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain
| | - Antonio Fernandez-Nebro
- UGC de Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain
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Fragoulis GE, Panayotidis I, Nikiphorou E. Cardiovascular Risk in Rheumatoid Arthritis and Mechanistic Links: From Pathophysiology to Treatment. Curr Vasc Pharmacol 2020; 18:431-446. [PMID: 31258091 DOI: 10.2174/1570161117666190619143842] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 05/22/2019] [Accepted: 05/22/2019] [Indexed: 12/19/2022]
Abstract
Rheumatoid arthritis (RA) is an autoimmune inflammatory arthritis. Inflammation, however, can spread beyond the joints to involve other organs. During the past few years, it has been well recognized that RA associates with increased risk for cardiovascular (CV) disease (CVD) compared with the general population. This seems to be due not only to the increased occurrence in RA of classical CVD risk factors and comorbidities like smoking, obesity, hypertension, diabetes, metabolic syndrome, and others but also to the inflammatory burden that RA itself carries. This is not unexpected given the strong links between inflammation and atherosclerosis and CVD. It has been shown that inflammatory cytokines which are present in abundance in RA play a significant role in every step of plaque formation and rupture. Most of the therapeutic regimes used in RA treatment seem to offer significant benefits to that end. However, more studies are needed to clarify the effect of these drugs on various parameters, including the lipid profile. Of note, although pharmacological intervention significantly helps reduce the inflammatory burden and therefore the CVD risk, control of the so-called classical risk factors is equally important. Herein, we review the current evidence for the underlying pathogenic mechanisms linking inflammation with CVD in the context of RA and reflect on the possible impact of treatments used in RA.
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Affiliation(s)
- George E Fragoulis
- Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, United Kingdom
| | - Ismini Panayotidis
- Faculty of Medical Sciences, Medical School, University College London, London, United Kingdom
| | - Elena Nikiphorou
- Department of Inflammation Biology, King's College London, London, UK and Department of Rheumatology, King's College Hospital, London, United Kingdom
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Mena-Vázquez N, Rojas-Gimenez M, Jimenez Nuñez FG, Manrique-Arija S, Rioja J, Ruiz-Limón P, Ureña I, Castro-Cabezas M, Valdivielso P, Fernández-Nebro A. Postprandial Apolipoprotein B48 is Associated with Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis. J Clin Med 2020; 9:E2483. [PMID: 32748862 PMCID: PMC7465472 DOI: 10.3390/jcm9082483] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 07/23/2020] [Accepted: 07/31/2020] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE To describe postprandial lipemia in patients with rheumatoid arthritis (RA) and to analyze its association with subclinical atherosclerosis measured as carotid intima-media thickness (cIMT). METHODS We performed an observational study of 40 patients with RA and 40 sex and age-matched controls. Patients with dyslipidemia were excluded. Pathologically increased cIMT was defined as a carotid thickness greater than the 90th percentile (>p90) for age and sex. Fasting and postprandial plasma lipids, cholesterol, triglycerides, apolipoprotein B48 (ApoB48), and total ApoB were evaluated. The other variables included were clinical and laboratory values, Framingham score, and the 28-joint Disease Activity Score (DAS28). Two multivariate models were constructed to identify factors associated with pathologic cIMT in patients with RA. RESULTS Fasting lipid values were similar in patients with RA and controls, although those of postprandial ApoB48 were higher (median (IQR), 14.4 (10.8-12.1) vs. 12.1 (2.3-9,8); p = 0.042). Pathologic cIMT was recorded in 10 patients with RA (25%) and nine controls (22.5%). In patients with RA, pathologic cIMT was associated with postprandial ApoB48 (OR (95% CI), 1.15 (1.0-1.3)) and total ApoB (OR [95% CI], 1.12 [1.1-1.2]). The second model revealed a mean increase of 0.256 mm for cIMT in patients with elevated anticitrullinated protein antibodies (ACPAs). CONCLUSION Postprandial ApoB48 levels in patients with RA are higher than in controls. Postprandial ApoB48 and total ApoB levels and markers of severity, such as ACPAs, are associated with pathologic cIMT in patients with RA. Our findings could indicate that these atherogenic particles have a negative effect on the endothelium.
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Affiliation(s)
- Natalia Mena-Vázquez
- The Institute of Biomedical Research in Malaga (IBIMA), 29010 Málaga, Spain; (N.M.-V.); (F.G.J.N.); (S.M.-A.); (J.R.); (P.R.-L.); (I.U.); (P.V.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Málaga, Spain
| | - Marta Rojas-Gimenez
- UGC de Reumatología, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia, 14004 Córdoba, Spain
| | - Francisco Gabriel Jimenez Nuñez
- The Institute of Biomedical Research in Malaga (IBIMA), 29010 Málaga, Spain; (N.M.-V.); (F.G.J.N.); (S.M.-A.); (J.R.); (P.R.-L.); (I.U.); (P.V.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Málaga, Spain
| | - Sara Manrique-Arija
- The Institute of Biomedical Research in Malaga (IBIMA), 29010 Málaga, Spain; (N.M.-V.); (F.G.J.N.); (S.M.-A.); (J.R.); (P.R.-L.); (I.U.); (P.V.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Málaga, Spain
| | - José Rioja
- The Institute of Biomedical Research in Malaga (IBIMA), 29010 Málaga, Spain; (N.M.-V.); (F.G.J.N.); (S.M.-A.); (J.R.); (P.R.-L.); (I.U.); (P.V.); (A.F.-N.)
- Departamento de Medicina y Dermatología, Universidad de Málaga, 29010, Málaga, Spain
| | - Patricia Ruiz-Limón
- The Institute of Biomedical Research in Malaga (IBIMA), 29010 Málaga, Spain; (N.M.-V.); (F.G.J.N.); (S.M.-A.); (J.R.); (P.R.-L.); (I.U.); (P.V.); (A.F.-N.)
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Clínico Virgen de la Victoria, 29010 Málaga, Spain
| | - Inmaculada Ureña
- The Institute of Biomedical Research in Malaga (IBIMA), 29010 Málaga, Spain; (N.M.-V.); (F.G.J.N.); (S.M.-A.); (J.R.); (P.R.-L.); (I.U.); (P.V.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Málaga, Spain
| | - Manuel Castro-Cabezas
- Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Kleiweg 500, 3045 PM Rotterdam, The Netherlands;
| | - Pedro Valdivielso
- The Institute of Biomedical Research in Malaga (IBIMA), 29010 Málaga, Spain; (N.M.-V.); (F.G.J.N.); (S.M.-A.); (J.R.); (P.R.-L.); (I.U.); (P.V.); (A.F.-N.)
- Departamento de Medicina y Dermatología, Universidad de Málaga, 29010, Málaga, Spain
- UGC de Medicina Interna, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, 29010 Málaga, Spain
| | - Antonio Fernández-Nebro
- The Institute of Biomedical Research in Malaga (IBIMA), 29010 Málaga, Spain; (N.M.-V.); (F.G.J.N.); (S.M.-A.); (J.R.); (P.R.-L.); (I.U.); (P.V.); (A.F.-N.)
- UGC de Reumatología, Hospital Regional Universitario de Málaga, 29009 Málaga, Spain
- Departamento de Medicina y Dermatología, Universidad de Málaga, 29010, Málaga, Spain
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Evaluation of the relationship between Behcet's disease and cardiovascular disorders through metabolic function and copeptin. Postepy Dermatol Alergol 2019; 36:609-615. [PMID: 31839779 PMCID: PMC6906967 DOI: 10.5114/ada.2019.89509] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Accepted: 06/15/2018] [Indexed: 11/17/2022] Open
Abstract
Introduction Behcet's disease (BD) is a chronic inflammatory and multisystem vasculitis. Cardiac involvement is one of the major complications of BD. Cardiac involvement is sporadic in terms of its specific relationship to mortality. How to identify and follow up on cardiac-related complications in BD patients has yet to be determined. Aim The aim of our study is to assess cardiovascular diseases in BD patients by measuring metabolic function and copeptin levels and comparing these to a healthy control group. Knowing the specific metabolic functions that are negatively affected by BD will help doctors determine which functions need to be more closely monitored in BD patients. Our study is the first study in the available literature that evaluates copeptin in BD patients. Material and methods A control group of 58 healthy volunteers, including 32 females and 26 males (average age: 39.8 ±10.3 years, range: 18-50 years), was formed to compare with 84 BD patients (average age: 40.5 ±11 years, range: 21-63 years), including 39 females and 45 males. Diastolic and systolic blood pressure, height, weight, body mass index (BMI), and waistline were measured for both groups. All study patients were also given hemograms, and fasting blood sugar (FBS), uric acid, lipid profile, insulin, C-reactive protein (CRP), and copeptin levels were measured. An ELISA Kit was used to measure copeptin. Results FBS, CRP, and insulin levels were significantly higher in the patient group (p < 0.001, p = 0.004, and p = 0.038, respectively). Patients who had had the disease for more than 10 years had higher BMIs, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels (p = 0.034, p = 0.004, p = 0.016, and p = 0.045, respectively). Additionally, CRP levels were found to be higher in long-term patients and patients with active lesions. Diastolic blood pressure and waist circumference were also higher in the BD group. Patients who had active lesions had significantly higher diastolic blood pressure (p = 0.047). There were no statistically significant differences in copeptin levels between BD and control groups. Conclusions Cardiovascular involvement rarely contributes to the high mortality rate of BD patients. There were meaningful elevations in metabolic markers identified when BD and cardiovascular disease risk was assessed with metabolic parameters. The cardiac disease risk should be closely followed using metabolic functions, particularly in long-term BD patients with vascular involvement.
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Guin A, Sinhamahapatra P, Misra S, Choudhury Mazumder SR, Chatterjee S, Ghosh A. Incidence and effect of insulin resistance on progression of atherosclerosis in rheumatoid arthritis patients of long disease duration. Biomed J 2019; 42:394-402. [PMID: 31948603 PMCID: PMC6962725 DOI: 10.1016/j.bj.2019.01.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Revised: 11/06/2018] [Accepted: 01/22/2019] [Indexed: 01/22/2023] Open
Abstract
Background The continued atherosclerotic risk in rheumatoid arthritis (RA) has been inadequately explained by conventional factors. Chronic inflammation and endothelial activation seems responsible for developing insulin resistance (IR). The study was aimed to assess the role of inflammation and endothelial activation causing IR in long term RA patients leading to increased atherosclerotic risk. Methods Fifty (25 long-duration and 25 short-duration) RA patients and twenty-three healthy controls were recruited excluding potential confounding co-morbidities. Fasting insulin, proinflammatory cytokines, endothelial stress markers and adipokines were quantified by ELISA. Homeostasis Model Assessment (HOMA)-IR calculated using glucose and insulin values. Atherosclerotic indices were measured using ultrasound. Results Lipid profile was comparable among groups. Mean carotid intima media thickness (cIMT) was significantly higher in both RA groups (p = 0.0062) compared to controls. HOMA-IR was significantly higher in long-duration RA (p = 0.005); it showed significant associations with DAS 28 (p = 0.01) and hsCRP (p = 0.03) in this subset. Mean cIMT for short-duration RA (p = 0.02) and long-duration RA (p = 0.0006) respectively was also significantly associated with HOMA-IR. Pro-inflammatory markers like TNF-α, resistin and leptin were highest in long-duration RA, higher in short-duration RA when compared to control group respectively. HOMA-IR was significantly dependent on TNF-α (p = 0.008), resistin (p = 0.031), leptin (p = 0.0054). Mean cIMT showed association with all parameters mainly with TNF-α (p = 0.001), iNOS (p = 0.001), resistin (p = 0.008) and leptin (p = 0.04). Conclusions Persistent inflammation leads to altered adipokine secretion promoting IR in RA patients with long disease duration. Treatment with conventional disease modifying anti-rheumatic drugs (DMARDs) is incomplete to control chronic inflammation and limit progression of atherosclerosis.
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Affiliation(s)
- Aharna Guin
- Department of Rheumatology, Institute of Postgraduate Medical Education and Research, SSKM Hospital, Kolkata, India
| | - Pradyot Sinhamahapatra
- Department of Rheumatology, Institute of Postgraduate Medical Education and Research, SSKM Hospital, Kolkata, India
| | - Sanchaita Misra
- Department of Rheumatology, Institute of Postgraduate Medical Education and Research, SSKM Hospital, Kolkata, India
| | | | - Sudipta Chatterjee
- Department of Rheumatology, Institute of Postgraduate Medical Education and Research, SSKM Hospital, Kolkata, India
| | - Alakendu Ghosh
- Department of Rheumatology, Institute of Postgraduate Medical Education and Research, SSKM Hospital, Kolkata, India.
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Serum retinol-binding protein 4 is associated with insulin resistance in patients with early and untreated rheumatoid arthritis. Joint Bone Spine 2019; 86:335-341. [DOI: 10.1016/j.jbspin.2018.07.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Accepted: 07/01/2018] [Indexed: 01/07/2023]
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Perry BI, Upthegrove R, Thompson A, Marwaha S, Zammit S, Singh SP, Khandaker G. Dysglycaemia, Inflammation and Psychosis: Findings From the UK ALSPAC Birth Cohort. Schizophr Bull 2019; 45:330-338. [PMID: 29635418 PMCID: PMC6403055 DOI: 10.1093/schbul/sby040] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Psychosis is associated with both dysglycaemia and low-grade inflammation, but population-based studies investigating the interplay between these factors are scarce. AIMS (1) To explore the direction of association between markers of dysglycaemia, inflammation and psychotic experiences (PEs); and (2) To explore whether dysglycaemia moderates and/or mediates the association between inflammation and PEs. METHOD Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were modeled using logistic and linear regression to examine cross-sectional and longitudinal associations between markers of dysglycaemia (ages 9 and 18), interleukin-6 (IL-6) (age 9), and PEs (ages 12 and 18). We tested for an interaction between dysglycaemia and IL-6 on risk of PEs at age 18, and tested whether dysglycaemia mediated the relationship between IL-6 and PEs. RESULTS Based on 2627 participants, at age 18, insulin resistance (IR) was associated with PEs (adjusted OR = 2.32; 95% CI, 1.37-3.97). IR was associated with IL-6 both cross-sectionally and longitudinally. Interaction analyses under a multiplicative model showed that IR moderated the association between IL-6 at age 9 and PEs at age 18 (adjusted OR for interaction term = 2.18; 95% C.I., 1.06-4.49). Mediation analysis did not support a model of IR mediating the relationship between IL-6 and PEs. IMPLICATIONS IR is associated with PEs in young people even before the onset of clinical psychosis. Metabolic alterations may interact with childhood inflammation to increase risk of PEs. The findings have implications for clinical practice and future research.
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Affiliation(s)
- Benjamin Ian Perry
- Department of Psychiatry, Coventry and Warwickshire Partnership NHS Trust, Coventry, UK
- Unit of Mental Health and Wellbeing, University of Warwick, Coventry, UK
| | - Rachel Upthegrove
- Insitute for Mental Health, University of Birmingham, Birmingham, UK
- Department of Psychiatry, Birmingham and Solihull Mental Health Foundation Trust, Birmingham, UK
| | - Andrew Thompson
- Department of Psychiatry, Coventry and Warwickshire Partnership NHS Trust, Coventry, UK
- Unit of Mental Health and Wellbeing, University of Warwick, Coventry, UK
| | - Steven Marwaha
- Department of Psychiatry, Coventry and Warwickshire Partnership NHS Trust, Coventry, UK
- Unit of Mental Health and Wellbeing, University of Warwick, Coventry, UK
| | - Stanley Zammit
- Centre for Academic Mental Health, School of Social and Community Medicine, University of Bristol, Bristol, UK
- Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
| | - Swaran Preet Singh
- Department of Psychiatry, Coventry and Warwickshire Partnership NHS Trust, Coventry, UK
- Unit of Mental Health and Wellbeing, University of Warwick, Coventry, UK
| | - Golam Khandaker
- Centre for Academic Mental Health, School of Social and Community Medicine, University of Bristol, Bristol, UK
- Department of Psychiatry, University of Cambridge, Cambridge, UK
- National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK
- Department of Psychiatry, Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge, UK
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19
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Rheumatoid Arthritis: Atherosclerosis Imaging and Cardiovascular Risk Assessment Using Machine and Deep Learning-Based Tissue Characterization. Curr Atheroscler Rep 2019; 21:7. [PMID: 30684090 DOI: 10.1007/s11883-019-0766-x] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE OF THE REVIEW Rheumatoid arthritis (RA) is a chronic, autoimmune disease which may result in a higher risk of cardiovascular (CV) events and stroke. Tissue characterization and risk stratification of patients with rheumatoid arthritis are a challenging problem. Risk stratification of RA patients using traditional risk factor-based calculators either underestimates or overestimates the CV risk. Advancements in medical imaging have facilitated early and accurate CV risk stratification compared to conventional cardiovascular risk calculators. RECENT FINDING In recent years, a link between carotid atherosclerosis and rheumatoid arthritis has been widely discussed by multiple studies. Imaging the carotid artery using 2-D ultrasound is a noninvasive, economic, and efficient imaging approach that provides an atherosclerotic plaque tissue-specific image. Such images can help to morphologically characterize the plaque type and accurately measure vital phenotypes such as media wall thickness and wall variability. Intelligence-based paradigms such as machine learning- and deep learning-based techniques not only automate the risk characterization process but also provide an accurate CV risk stratification for better management of RA patients. This review provides a brief understanding of the pathogenesis of RA and its association with carotid atherosclerosis imaged using the B-mode ultrasound technique. Lacunas in traditional risk scores and the role of machine learning-based tissue characterization algorithms are discussed and could facilitate cardiovascular risk assessment in RA patients. The key takeaway points from this review are the following: (i) inflammation is a common link between RA and atherosclerotic plaque buildup, (ii) carotid ultrasound is a better choice to characterize the atherosclerotic plaque tissues in RA patients, and (iii) intelligence-based paradigms are useful for accurate tissue characterization and risk stratification of RA patients.
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20
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Small HY, Migliarino S, Czesnikiewicz-Guzik M, Guzik TJ. Hypertension: Focus on autoimmunity and oxidative stress. Free Radic Biol Med 2018; 125:104-115. [PMID: 29857140 DOI: 10.1016/j.freeradbiomed.2018.05.085] [Citation(s) in RCA: 83] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2018] [Revised: 05/22/2018] [Accepted: 05/28/2018] [Indexed: 12/25/2022]
Abstract
Understanding the causal role of the immune and inflammatory responses in hypertension has led to questions regarding the links between hypertension and autoimmunity. Immune pathology in primary hypertension mimics several autoimmune mechanisms observed in the pathogenesis of systemic lupus erythematosus, psoriasis, systemic sclerosis, rheumatoid arthritis and periodontitis. More importantly, the prevalence of hypertension in patients with these autoimmune diseases is significantly increased, when compared to control populations. Clinical and epidemiological evidence is reviewed along with possible mechanisms linking hypertension and autoimmunity. Inflammation and oxidative stress are linked in a self-perpetuating cycle that significantly contributes to the vascular dysfunction and renal damage associated with hypertension. T cell, B cell, macrophage and NK cell infiltration into these organs is essential for this pathology. Effector cytokines such as IFN-γ, TNF-α and IL-17 affect Na+/H+ exchangers in the kidney. In blood vessels, they lead to endothelial dysfunction and loss of nitric oxide bioavailability and cause vasoconstriction. Both renal and vascular effects are, in part, mediated through induction of reactive oxygen species-producing enzymes such as superoxide anion generating NADPH oxidases and dysfunction of anti-oxidant systems. These mechanisms have recently become important therapeutic targets of novel therapies focused on scavenging oxidative (isolevuglandin) modification of neo-antigenic peptides. Effects of classical immune targeted therapies focused on immunosuppression and anti-cytokine treatments are also reviewed.
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Affiliation(s)
- Heather Y Small
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Serena Migliarino
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Marta Czesnikiewicz-Guzik
- Oral Sciences Research Group, Glasgow Dental School, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK; Department of Dental Prophylaxis and Experimental Dentistry, Dental School of Jagiellonian University, Krakow, Poland
| | - Tomasz J Guzik
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK; Department of Internal and Agricultural Medicine, Jagiellonian University Collegium Medicum, Krakow, Poland.
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21
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Arias de la Rosa I, Escudero-Contreras A, Rodríguez-Cuenca S, Ruiz-Ponce M, Jiménez-Gómez Y, Ruiz-Limón P, Pérez-Sánchez C, Ábalos-Aguilera MC, Cecchi I, Ortega R, Calvo J, Guzmán-Ruiz R, Malagón MM, Collantes-Estevez E, Vidal-Puig A, López-Pedrera C, Barbarroja N. Defective glucose and lipid metabolism in rheumatoid arthritis is determined by chronic inflammation in metabolic tissues. J Intern Med 2018. [PMID: 29532531 DOI: 10.1111/joim.12743] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Rheumatoid arthritis (RA) patients are at increased risk of insulin resistance (IR); however, the specific mechanisms mediating this association are currently unknown. OBJECTIVE To investigate whether the inflammatory activity associated with RA accounts for the observed defective glucose metabolism and lipid metabolism in these patients. METHODS We followed two main strategies: (i) extensive metabolic profiling of a RA cohort of 100 patients and 50 healthy control subjects and (ii) mechanistic studies carried out in both a collagen-induced arthritis mouse model and 3T3-L1 adipocytes treated with conditioned serum from RA patients. RESULTS Following the exclusion of obese and diabetic subjects, data from RA patients demonstrated a strong link between the degree of systemic inflammation and the development of IR. These results were strengthened by the observation that induction of arthritis in mice resulted in a global inflammatory state characterized by defective carbohydrate and lipid metabolism in different tissues. Adipose tissue was most susceptible to the RA-induced metabolic alterations. These metabolic effects were confirmed in adipocytes treated with serum from RA patients. CONCLUSIONS Our results show that the metabolic disturbances associated with RA depend on the degree of inflammation and identify inflammation of adipose tissue as the initial target leading to IR and the associated molecular disorders of carbohydrate and lipid homeostasis. Thus, we anticipate that therapeutic strategies based on tighter control of inflammation and flares could provide promising approaches to normalize and/or prevent metabolic alterations associated with RA.
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Affiliation(s)
- I Arias de la Rosa
- Rheumatology Service, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
| | - A Escudero-Contreras
- Rheumatology Service, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
| | - S Rodríguez-Cuenca
- Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbroke's Hospital, University of Cambridge, Cambridge, UK
| | - M Ruiz-Ponce
- Rheumatology Service, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
| | - Y Jiménez-Gómez
- Rheumatology Service, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
| | - P Ruiz-Limón
- Rheumatology Service, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
| | - C Pérez-Sánchez
- Rheumatology Service, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
| | - M C Ábalos-Aguilera
- Rheumatology Service, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
| | - I Cecchi
- Rheumatology Service, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain.,Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy
| | - R Ortega
- Rheumatology Service, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
| | - J Calvo
- Rheumatology Service, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
| | - R Guzmán-Ruiz
- Department of Cell Biology, Physiology and Immunology, IMIBIC, Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain.,CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - M M Malagón
- Department of Cell Biology, Physiology and Immunology, IMIBIC, Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain.,CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - E Collantes-Estevez
- Rheumatology Service, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
| | - A Vidal-Puig
- Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbroke's Hospital, University of Cambridge, Cambridge, UK
| | - Ch López-Pedrera
- Rheumatology Service, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain
| | - N Barbarroja
- Rheumatology Service, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain.,CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
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22
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Jagpal A, Navarro-Millán I. Cardiovascular co-morbidity in patients with rheumatoid arthritis: a narrative review of risk factors, cardiovascular risk assessment and treatment. BMC Rheumatol 2018; 2:10. [PMID: 30886961 PMCID: PMC6390616 DOI: 10.1186/s41927-018-0014-y] [Citation(s) in RCA: 88] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Accepted: 02/28/2018] [Indexed: 12/19/2022] Open
Abstract
Cardiovascular disease (CVD) is markedly increased in patients with rheumatoid arthritis partly due to accelerated atherosclerosis from chronic inflammation. Traditional cardiovascular risk factors such as hypertension, hyperlipidemia, smoking, diabetes mellitus and physical inactivity are also highly prevalent among patients with rheumatoid arthritis (RA) and contribute to the CVD risk. The impact of traditional risk factors on the CVD risk appears to be different in the RA and non-RA population. However, hyperlipidemia, diabetes mellitus, body mass index and family history of CVD influence the CVD risk in RA patients the same way they do for the non-RA population. Despite that, screening and treatment of these risk factors is suboptimal among patients with RA. Recent guidelines from the European League Against Rheumatism (EULAR) recommend aggressive management of traditional risk factors in addition to RA disease activity control to decrease the CVD risk. Several CVD risk calculators are available for clinical use to stratify a patients' risk of developing a CVD event. Most of these calculators do not account for RA as a risk factor; thus, a multiplication factor of 1.5 is recommended to predict the risk more accurately. In order to reduce CVD in the RA population, national guidelines for the prevention of CVD should be applied to manage traditional risk factors in addition to aggressive control of RA disease activity. While current data suggests a protective effect of non-biologic disease modifying anti-rheumatic drugs (DMARDs) and biologics on cardiovascular events among patients with RA, more data is needed to define this effect more accurately.
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Affiliation(s)
- Aprajita Jagpal
- Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 836 Faculty Office Tower, 510 20th Street South, Birmingham, AL 35294 USA
| | - Iris Navarro-Millán
- Joan and Sanford I Weill Medical College of Cornell University, Division of General Internal Medicine, 525 East 68th Street, F-2019, PO Box #331, New York, NY 10065 USA
- Division of Rheumatology, Hospital for Special Surgery, New York, NY USA
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Ambrosino P, Lupoli R, Di Minno A, Tasso M, Peluso R, Di Minno MND. Subclinical atherosclerosis in patients with rheumatoid arthritis. Thromb Haemost 2017; 113:916-30. [DOI: 10.1160/th14-11-0921] [Citation(s) in RCA: 96] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2014] [Accepted: 12/31/2014] [Indexed: 12/16/2022]
Abstract
SummaryWe performed a systematic review with meta-analysis and meta-regression of literature studies evaluating the impact of rheumatoid arthritis (RA) on common carotid artery intima-media thickness (CCAIMT) and on the prevalence of carotid plaques. Studies evaluating the relationship between RA and markers of cardiovascular (CV) risk (CCA-IMT and prevalence of carotid plaques) were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. A total of 59 studies (4,317 RA patients and 3,606 controls) were included in the final analysis, 51 studies with data on CCA-IMT (52 data-sets on 3,600 RA patients and 3,020 controls) and 35 studies reporting on the prevalence of carotid plaques (2,859 RA patients and 2,303 controls). As compared to controls, RA patients showed a higher CCA-IMT (mean difference [MD]: 0.10 mm; 95 % confidence interval [CI]: 0.07, 0.12; p < 0.00001), and an increased prevalence of carotid plaques (odds ratio [OR]: 3.61; 95 %CI: 2.65, 4.93; p< 0.00001). Interestingly, when analysing studies on early RA, the difference in CCAIMT among RA patients and controls was even higher (MD: 0.21 mm; 95 %CI: 0.06, 0.35; p=0.006), and difference in the prevalence of carotid plaques was entirely confirmed (OR: 3.57; 95 %CI: 1.69, 7.51; p=0.0008). Meta-regression models showed that male gender and a more severe inflammatory status [as expressed by disease activity score in 28 joints (DAS28), C-reactive protein (CRP) levels, and erythrocyte sedimentation rate (ESR)] significantly impacted on CCA-IMT. In conclusion, RA appears significantly associated with subclinical atherosclerosis and CV risk. These findings can be useful to plan adequate prevention strategies and therapeutic approaches.
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24
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Use of Hydroxychloroquine Is Associated With Improved Lipid Profile in Rheumatoid Arthritis Patients. J Clin Rheumatol 2017; 23:144-148. [PMID: 28277344 DOI: 10.1097/rhu.0000000000000502] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
BACKGROUND/PURPOSE We examined the association between hydroxychloroquine (HCQ) and plasma lipid and glucose levels in rheumatoid arthritis (RA) cohort. METHODS This is a retrospective cohort analysis of 1261 RA patients comparing fasting lipid profiles and plasma glucose between patients who were and were not taking HCQ. We divided patients into 3 groups based on HCQ exposure during follow-up: those who had never taken HCQ, those who took it intermittently, and those who took it continuously. We used multivariable models and propensity scoring to compensate for the effect of nonrandom treatment assignment. RESULTS We followed 1261 RA patients for a total of 4605 observations between 1996 and 2014. After adjusting for age, sex, ethnicity, other disease-modifying antirheumatic drugs (DMARDs), lipid-lowering medications, body mass index (BMI), and smoking, patients taking HCQ at baseline had significantly lower total cholesterol (TC) (P ≤ 0.001), low-density lipoprotein (LDL) (P ≤ 0.001), triglycerides (P = 0.013), and lipid profile ratios TC/high-density lipoprotein (HDL) (P ≤ 0.001) and LDL/HDL (P ≤ 0.001), as well as higher HDL (P ≤ 0.001).In longitudinal analyses, after adjusting for confounders, patients who continuously took HCQ showed significantly lower TC, LDL, TC/HDL, and LDL/HDL and higher HDL (P ≤ 0.01). Fasting plasma glucose levels were not significantly associated with HCQ exposure. CONCLUSIONS Hydroxychloroquine use was associated with lower lipid levels but not with the plasma glucose in this RA cohort. These findings support the need for a randomized trial to establish the role of HCQ in cardiovascular disease prevention in RA patients.
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25
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Vitamin D Status, Disease Activity, and Endothelial Dysfunction in Early Rheumatoid Arthritis Patients. DISEASE MARKERS 2017; 2017:5241012. [PMID: 29200598 PMCID: PMC5671710 DOI: 10.1155/2017/5241012] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Revised: 09/16/2017] [Accepted: 09/28/2017] [Indexed: 02/06/2023]
Abstract
Cardiovascular diseases represent important complications in rheumatoid arthritis (RA) patients, generated by an accelerated atherosclerosis. The aim of this study is represented by the assessment of the correlations between serum levels of vitamin D, disease activity, and endothelial dysfunction in patients with early RA. Material and Methods. The study was performed on a group of 35 patients with early RA and 35 healthy subjects matched for age and gender, as controls. In all studied subjects, the following were determined: inflammatory markers, insulin resistance, vitamin D levels, and endothelial dysfunction. Statistical analysis were performed using the Student's t-test and the Pearson's test. p values of less than 0.05 were considered statistically significant. Results. The group of patients with RA patients presented inflammation, low levels of vitamin D, elevated insulin resistance, and reduced flow-mediated vasodilation, statistically significant compared to the control group (p < 0.00001). Significant inverse correlations between the levels of 25(OH) vitamin D and DAS28, respective insulin resistance, and significant positive correlation between 25(OH) vitamin D and endothelial function were demonstrated. Conclusion. In early RA patients with moderate and high disease activity, low serum levels of vitamin D were associated with disease activity, increased insulin resistance, and endothelial dysfunction.
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26
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Tejera-Segura B, López-Mejías R, Domínguez-Luis MJ, de Vera-González AM, González-Delgado A, Ubilla B, Olmos JM, Hernández JL, González-Gay MA, Ferraz-Amaro I. Incretins in patients with rheumatoid arthritis. Arthritis Res Ther 2017; 19:229. [PMID: 29041949 PMCID: PMC5645916 DOI: 10.1186/s13075-017-1431-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Accepted: 09/15/2017] [Indexed: 01/26/2023] Open
Abstract
Background The precise mechanism linking systemic inflammation with insulin resistance (IR) in rheumatoid arthritis (RA) remains elusive. In the present study, we determined whether the incretin-insulin axis and incretin effect are disrupted in patients with RA and if they are related to the IR found in these patients. Methods We conducted a cross-sectional study that encompassed 361 subjects without diabetes, 151 patients with RA, and 210 sex-matched control subjects. Insulin, C-peptide, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 (DPP-4) soluble form, and IR indexes by homeostatic model assessment (HOMA2) were assessed. A multivariable analysis adjusted for IR-related factors was performed. Additionally, ten patients and ten control subjects underwent a 566-kcal meal test so that we could further study the postprandial differences of these molecules between patients and control subjects. Results Insulin, C-peptide, and HOMA2-IR indexes were higher in patients than in control subjects. This was also the case for GLP-1 (0.49 ± 1.28 vs. 0.71 ± 0.22 ng/ml, p = 0.000) and GIP (0.37 ± 0.40 vs. 1.78 ± 0.51 ng/ml, p = 0.000). These differences remained significant after multivariable adjustment including glucocorticoid intake. Disease Activity Score in 28 joints with erythrocyte sedimentation rate (β coefficient 46, 95% CI 6–87, p = 0.026) and Clinical Disease Activity Index (β coefficient 7.74, 95% CI 1.29–14.20, p = 0.019) were associated with DPP-4 serum levels. GLP-1 positively correlated with β-cell function (HOMA2 of β-cell production calculated with C-peptide) in patients but not in control subjects (interaction p = 0.003). The meal test in patients with RA revealed a higher total and late response AUC for glucose response, a later maximal response of C-peptide, and a flatter curve in GIP response. Conclusions The incretin-insulin axis, both during fasting and postprandial, is impaired in patients with RA. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1431-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Beatriz Tejera-Segura
- Division of Rheumatology, Hospital Universitario de Canarias, 38320, Tenerife, Spain
| | - Raquel López-Mejías
- Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain
| | | | | | - Alejandra González-Delgado
- Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - Begoña Ubilla
- Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - José M Olmos
- Division of Internal Medicine, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Santander, Spain
| | - José L Hernández
- Division of Internal Medicine, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Santander, Spain
| | - Miguel A González-Gay
- Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain. .,Division of Rheumatology, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain. .,School of Medicine, University of Cantabria, Santander, Spain. .,Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
| | - Iván Ferraz-Amaro
- Division of Rheumatology, Hospital Universitario de Canarias, 38320, Tenerife, Spain.
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27
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Noorwali A, Omran N, Elmedany SH, El-Barbary AM. Risk factors for acute coronary events in patients with rheumatoid arthritis. EGYPTIAN RHEUMATOLOGY AND REHABILITATION 2017. [DOI: 10.4103/err.err_14_17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Nah SS, Lee H, Hong Y, Im J, Won H, Chang SH, Kim HK, Kwon JT, Kim HJ. Association between endothelin‑1 and fibromyalgia syndrome. Mol Med Rep 2017; 16:6234-6239. [PMID: 28901422 DOI: 10.3892/mmr.2017.7395] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 08/01/2017] [Indexed: 11/06/2022] Open
Abstract
Fibromyalgia syndrome (FMS) is characterized by widespread chronic musculoskeletal pain, stiffness and pressure hyperalgesia at soft tissue tender points. Patients with FMS may exhibit a tendency towards cold extremities and cold‑induced vasospasm. Endothelin‑1 (EDN1) is a potent vasoconstrictor that is mainly produced by endothelial cells. The present study aimed to determine whether plasma expression levels avvnd single‑nucleotide polymorphism (SNP; rs1800541) of the EDN1 gene were associated with FMS and/or any of its clinical variables. Plasma EDN1 levels were assessed by ELISA, and SNP genotypes were determined using polymerase chain reaction‑high‑resolution melting curve analysis. Patients with the TG genotype and the G allele may have an elevated risk of FMS. In addition, patients with FMS with the TG genotype and/or T allele exhibited higher plasma EDN1 levels compared with healthy controls. EDN1 levels increased significantly in patients with FMS compared with normal controls. In addition, EDN1 SNP was found to be associated with susceptibility to FMS.
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Affiliation(s)
- Seong-Su Nah
- Division of Rheumatology, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam 31151, Republic of Korea
| | - Hwayoung Lee
- Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam 31151, Republic of Korea
| | - Yeongseon Hong
- Division of Rheumatology, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam 31151, Republic of Korea
| | - Jiyun Im
- Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam 31151, Republic of Korea
| | - Hansol Won
- Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam 31151, Republic of Korea
| | - Sung-Hae Chang
- Division of Rheumatology, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam 31151, Republic of Korea
| | - Hyung-Ki Kim
- Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam 31151, Republic of Korea
| | - Jun-Tack Kwon
- Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam 31151, Republic of Korea
| | - Hak-Jae Kim
- Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam 31151, Republic of Korea
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Müller R, Kull M, Lember M, Põlluste K, Valner A, Kallikorm R. Insulin Resistance in Early Rheumatoid Arthritis Is Associated with Low Appendicular Lean Mass. BIOMED RESEARCH INTERNATIONAL 2017; 2017:9584720. [PMID: 28932748 PMCID: PMC5592389 DOI: 10.1155/2017/9584720] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Revised: 07/05/2017] [Accepted: 07/25/2017] [Indexed: 02/08/2023]
Abstract
In established rheumatoid arthritis (RA), the presence of insulin resistance (IR) is well proven but, in the early stage of the disease, data are inconclusive. We evaluated the presence of IR and associations with body composition (BC) parameters among early RA (ERA) and control subjects. The study group consisted of 92 ERA and 321 control subjects. Using homeostatic model assessment of IR (HOMA-IR), the cut-off value for IR was 2.15. 56% of the ERA patients and 25% of the controls had IR. Of the BC parameters, patients with early RA had less fat-free mass and appendicular lean mass (ALM). In multivariable model, ERA group (b-Coefficient) (4.8, CI: 2.6-8.8), male gender (7.7, CI: 2.7-22.1), and fat mass index (1.2, CI: 1.1-1.4) were associated with IR. Insulin-resistant ERA patients had higher inflammatory markers and higher disease activity. In the multivariable model in the ERA group, IR was associated with male gender (b-Coefficient) (7.4, CI: 153-34.9), high disease activity (6.2, CI: 1.7-22.2), and lower ALM (0.03, CI: 0.001-0.97). IR develops in the early stage of RA in the majority of patients. IR is more common among males and is associated with RA disease activity and lower ALM.
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Affiliation(s)
- Raili Müller
- Institute of Clinical Medicine, University of Tartu, L. Puusepa 8, 51014 Tartu, Estonia
- Internal Medicine Clinic, Tartu University Hospital, L. Puusepa 8, 51014 Tartu, Estonia
| | - Mart Kull
- Institute of Clinical Medicine, University of Tartu, L. Puusepa 8, 51014 Tartu, Estonia
- Internal Medicine Clinic, Tartu University Hospital, L. Puusepa 8, 51014 Tartu, Estonia
| | - Margus Lember
- Institute of Clinical Medicine, University of Tartu, L. Puusepa 8, 51014 Tartu, Estonia
- Internal Medicine Clinic, Tartu University Hospital, L. Puusepa 8, 51014 Tartu, Estonia
| | - Kaja Põlluste
- Institute of Clinical Medicine, University of Tartu, L. Puusepa 8, 51014 Tartu, Estonia
| | - Annika Valner
- Institute of Clinical Medicine, University of Tartu, L. Puusepa 8, 51014 Tartu, Estonia
- Internal Medicine Clinic, Tartu University Hospital, L. Puusepa 8, 51014 Tartu, Estonia
| | - Riina Kallikorm
- Institute of Clinical Medicine, University of Tartu, L. Puusepa 8, 51014 Tartu, Estonia
- Internal Medicine Clinic, Tartu University Hospital, L. Puusepa 8, 51014 Tartu, Estonia
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Bartoloni E, Alunno A, Gerli R. Hypertension as a cardiovascular risk factor in autoimmune rheumatic diseases. Nat Rev Cardiol 2017; 15:33-44. [PMID: 28836617 DOI: 10.1038/nrcardio.2017.118] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Evidence for the increased risk of cardiovascular morbidity and mortality in patients with chronic inflammatory and systemic autoimmune diseases has accumulated during the past 15 years. In these patients, an interplay between several mechanisms, including premature acceleration of subclinical atherosclerotic damage, inflammation, and dysregulation of the immune system, is involved in the induction and progression of atherosclerosis. Moreover, traditional cardiovascular risk factors are also likely to contribute, at least in part, to the excess cardiovascular risk. Among traditional cardiovascular risk factors, hypertension is an important predictor of cardiovascular events in the general population and in patients with chronic inflammatory and autoimmune diseases. Evidence supports the idea that the pathogenic mechanisms underlying the increased blood pressure in these diseases are multifactorial and not only related to the mechanical injury of the arterial wall. In particular, chronic inflammation and immune-mediated mechanisms have been demonstrated to affect blood-pressure control in patients with systemic autoimmune disease. In this Review, we discuss the available evidence on the relationship between hypertension and autoimmune diseases, and describe the multiple factors that might affect blood-pressure control in patients with chronic inflammatory and systemic autoimmune diseases. We also discuss the effect of hypertension and antirheumatic therapies on cardiovascular outcome.
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Affiliation(s)
- Elena Bartoloni
- Rheumatology Unit, Department of Medicine, University of Perugia, P.le Menghini 1, Perugia 06129, Italy
| | - Alessia Alunno
- Rheumatology Unit, Department of Medicine, University of Perugia, P.le Menghini 1, Perugia 06129, Italy
| | - Roberto Gerli
- Rheumatology Unit, Department of Medicine, University of Perugia, P.le Menghini 1, Perugia 06129, Italy
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Wu D, Hua B, Fang Z, Liu J, Liu N, Ma Y. Adiponectin exerts a potent anti-arthritic effect and insulin resistance in collagen-induced arthritic rats. Int J Rheum Dis 2017; 21:1496-1503. [PMID: 28752573 DOI: 10.1111/1756-185x.13141] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIM Previous research has shown that adiponectin (AD) induces severe insulin resistance (IR) and exhibits pro-inflammatory effect, so it could serve as a useful risk biomarker in rheumatoid arthritis (RA). The present study aims to evaluate the effect of AD on IR and anti-arthritis in collagen-induced arthritic (CIA) rats. METHOD After immunization with bovine type II collagen (CII), Wistar rats were administered with AD (60 μg/kg/day) or saline into the ankle joint cavity of the left hind leg for 15 days. The severity of arthritis was clinically and histologically assessed. Arthritis score was recorded every other day for each paw. Paw volume was measured on alternate days to monitor the progression of the disease in the arthritic control group. Tumor necrosis factor (TNF)-α, interleukin (IL)-1, AD, insulin and fasting glucose were measured in sera. Histopathology of joint synovial tissues was also examined. RESULTS Treatment with AD resulted in significantly delayed onset of arthritis as well as decreased clinical arthritis and histopathological severity scores. AD reduced both serum fasting glucose, TNF-α, IL-1 and IR. Histological analysis confirmed treatment with AD suppressed joint synovial inflammation and immunohistochemical expression of TNF-α compared to the CIA group. Surprisingly, adiponectin levels measured by enzyme-linked immunosorbent assay in serum were significantly increased in CIA rats compared to the normal group. CONCLUSIONS Adiponectin might display anti-inflammatory effects. These results suggest that AD may be a potential immunosuppressant for the treatment of RA linked to metabolic disease.
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Affiliation(s)
- Dongke Wu
- Department of Internal Clinical Medicine, the first Affiliated Hospital of Nanchang University, Nanchang, China
| | - Binghong Hua
- The Medical School of Nanchang University, Nanchang, China
| | - Zishui Fang
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Jiankun Liu
- The Medical School of Nanchang University, Nanchang, China
| | - Ningning Liu
- The Medical School of Nanchang University, Nanchang, China
| | - Yunqing Ma
- Department of Internal Clinical Medicine, the first Affiliated Hospital of Nanchang University, Nanchang, China.,Department of Rheumatology, UTHealth Medical School at Houston, Houston, Texas, USA
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Gomes KWP, Luz AJP, Felipe MRDB, Beltrão LA, Sampaio AXC, Rodrigues CEM. Prevalence of metabolic syndrome in rheumatoid arthritis patients from Northeastern Brazil: Association with disease activity. Mod Rheumatol 2017; 28:258-263. [DOI: 10.1080/14397595.2017.1316813] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Kirla Wagner Poti Gomes
- Department of Rheumatology, Hospital Geral de Fortaleza, Ceará, Brazil
- Post-Graduate Program in Medical Sciences, University of Fortaleza (UNIFOR), Ceará, Brazil
| | | | | | | | | | - Carlos Ewerton Maia Rodrigues
- Post-Graduate Program in Medical Sciences, University of Fortaleza (UNIFOR), Ceará, Brazil
- Federal University of Ceará, Ceará, Brazil
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Hallajzadeh J, Safiri S, Mansournia MA, Khoramdad M, Izadi N, Almasi-Hashiani A, Pakzad R, Ayubi E, Sullman MJM, Karamzad N. Metabolic syndrome and its components among rheumatoid arthritis patients: A comprehensive updated systematic review and meta-analysis. PLoS One 2017; 12:e0170361. [PMID: 28333949 PMCID: PMC5363810 DOI: 10.1371/journal.pone.0170361] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 01/03/2017] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Estimating the current global prevalence of metabolic syndrome (MetS), and its components, among rheumatoid arthritis (RA) patients is necessary in order to formulate preventative strategies and to ensure there are adequate community resources available for these patients. Furthermore, the association between RA and MetS is controversial and has not previously been comprehensively assessed. Therefore, the present study aimed to: 1) determine the prevalence of MetS, and its components, among RA patients across the world 2) update the odds ratio of MetS in RA patients, compared to healthy controls, using a comprehensive systematic review and meta-analysis. METHODS International databases, including: the Web of Science, PubMed, Scopus, Embase, CINAHL and other relevant databases were searched to identify English language articles which reported the prevalence and risk of MetS in RA patients between January 2000 and August 2016. The meta-analysis only included studies which clearly described the time and location of the study, utilised adequate sampling strategies, and appropriate statistical analyses. RESULTS The meta-analyses of prevalence (70 studies [n = 12612]) and risk (43 studies [n = 35220]) of MetS in RA patients were undertaken separately. The overall pooled prevalence of MetS was 30.65% (95% CI: 27.87-33.43), but this varied from 14.32% (95% CI: 10.59-18.05) to 37.83% (95% CI: 31.05-44.61), based upon the diagnostic criteria used. The prevalence of MetS also varied slightly between males (31.94%, 95% CI: 24.37-39.51) and females (33.03%, 95% CI: 28.09-37.97), but this was not statistically significant. The overall pooled odds ratio (OR) of MetS in RA patients, compared to healthy controls, was 1.44 (95% CI: 1.20-1.74), but this ranged from 0.70 (95% CI: 0.27-1.76) to 4.09 (95% CI: 2.03-8.25), depending on the criteria used. The mean age and diagnostic criteria of MetS were identified as sources of heterogeneity in the estimated odds ratios between studies (P<0.05). CONCLUSIONS According to the high prevalence of MetS in RA patients, and high risk of MetS, measuring metabolic syndrome in RA patients is strongly recommended. Furthermore, as high waist circumference (WC) is the most common metabolic syndrome component, more attention must be paid to nutrition and weight loss among those with RA.
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Affiliation(s)
- Jamal Hallajzadeh
- Department of Community Nutrition, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Managerial Epidemiology Research Center, Department of Public Health, School of Nursing and Midwifery, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Saeid Safiri
- Managerial Epidemiology Research Center, Department of Public Health, School of Nursing and Midwifery, Maragheh University of Medical Sciences, Maragheh, Iran
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Ali Mansournia
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Maliheh Khoramdad
- Department of Epidemiology and Biostatistics, Faculty of Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Neda Izadi
- Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Almasi-Hashiani
- Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Centre, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Reza Pakzad
- Department of Epidemiology, Faculty of Health, Ilam University of Medical Sciences, Ilam, Iran
| | - Erfan Ayubi
- Department of Public Health, School of Public Health, Zabol University of Medical Sciences, Zabol, Iran
| | - Mark J. M. Sullman
- Driving Research Group, Cranfield University, Bedfordshire, United Kingdom
| | - Nahid Karamzad
- Vice-Chancellery for Food and Drug, Maragheh University of Medical Sciences, Maragheh, Iran
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The clinical value of anti-cyclic citrullinated peptide (anti-ccp) antibodies and insulin resistance (IR) in detection of early and subclinical atherosclerosis in rheumatoid arthritis (RA). Egypt Heart J 2016. [DOI: 10.1016/j.ehj.2015.01.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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Influence of Insulin Resistance and TNF-α on the Inflammatory Process, Oxidative Stress, and Disease Activity in Patients with Rheumatoid Arthritis. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:8962763. [PMID: 27340510 PMCID: PMC4906209 DOI: 10.1155/2016/8962763] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Accepted: 04/19/2016] [Indexed: 12/18/2022]
Abstract
The aim of this study was to evaluate the involvement of TNF-α and insulin resistance (IR) in the inflammatory process, oxidative stress, and disease activity in patients with rheumatoid arthritis (RA). This cross-sectional study included 270 subjects (control group, n = 97) and RA patients (n = 173). RA patients were divided into four groups: the first group without IR and not using antitumor necrosis factor-α (TNF−) (G1, IR− TNF−); the second group without IR and using anti-TNF-α (G2, IR− TNF+); the third group with IR and not using anti-TNF-α (G3, IR+ TNF−); and the fourth group with IR and using anti-TNF-α (G4, IR+ TNF+). G3 and G4 had higher (p < 0.05) advanced oxidation protein products (AOPPs) and oxidative stress index (OSI) compared to G1. G4 group presented higher (p < 0.05) AOPPs and OSI than G2. TRAP was significantly lower in G3 compared to G1. Plasma TNF-α levels were significantly higher in G4 and G2 compared to G1 (p < 0.0001) and G3 (p < 0.0001 and p < 0.01, resp.). The presence of insulin resistance was robustly associated with both oxidative stress and TNF-α levels. More studies are warranted to verify if IR can be involved in therapeutic failure with TNF-α inhibitors. This trial is registered with Brazilian Clinical Trials Registry Register number RBR-2jvj92.
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Uslu AU, Kucuk A, Balta S, Ozturk C, Arslan S, Tekin L, Kucuksen S, Toker A, Kayrak M. The relation between ischemia modified albumin levels and carotid intima media thickness in patients with rheumatoid arthritis. Int J Rheum Dis 2016; 22:32-37. [DOI: 10.1111/1756-185x.12851] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Affiliation(s)
- Ali U. Uslu
- Department of Internal Medicine; Eskisehir Military Hospital; Eskisehir Turkey
| | - Adem Kucuk
- Division of Rheumatology; Necmettin Erbakan University; Konya Turkey
| | - Sevket Balta
- Department of Cardiology; Gulhane Medical Faculty; Ankara Turkey
| | - Cengiz Ozturk
- Department of Cardiology; Gulhane Medical Faculty; Ankara Turkey
| | - Sevket Arslan
- Division of Allergy and Clinical Immunology; Necmettin Erbakan University; Konya Turkey
| | - Levent Tekin
- Department of Physical Medicine and Rehabilitation; Beyhekim State Hospital; Konya Turkey
| | - Sami Kucuksen
- Department of Physical Medicine and Rehabilitation; Necmettin Erbakan University; Konya Turkey
| | - Aysun Toker
- Department of Biochemistry; Necmettin Erbakan University; Konya Turkey
| | - Mehmet Kayrak
- Department of Cardiology; Necmettin Erbakan University; Konya Turkey
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Oliveira BMGBD, Medeiros MMDC, Cerqueira JVMD, Quixadá RTDS, Oliveira ÍMXD. Síndrome metabólica em pacientes com diagnóstico de artrite reumatoide acompanhados em um Hospital Universitário do Nordeste brasileiro. REVISTA BRASILEIRA DE REUMATOLOGIA 2016. [DOI: 10.1016/j.rbr.2015.05.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Sørensen AL, Hasselbalch HC. Antecedent cardiovascular disease and autoimmunity in Philadelphia-negative chronic myeloproliferative neoplasms. Leuk Res 2016; 41:27-35. [DOI: 10.1016/j.leukres.2015.11.017] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Revised: 11/14/2015] [Accepted: 11/28/2015] [Indexed: 01/07/2023]
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Kisiel B, Kruszewski R, Juszkiewicz A, Kłos K, Tłustochowicz M, Tłustochowicz W. Prevalence of Atherosclerosis in diabetic and non-diabetic patients with rheumatoid arthritis. Pak J Med Sci 2015; 31:1078-83. [PMID: 26648990 PMCID: PMC4641259 DOI: 10.12669/pjms.315.7620] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
Objectives: (1) To compare the prevalence of preclinical atherosclerosis in diabetic vs. non-diabetic rheumatoid arthritis (RA) patients; (2) to determine the influence of classical and RA-related factors on atherosclerosis; (3) to assess the usefulness of combined carotid and femoral ultrasonography in detecting atherosclerosis. Methods: The study comprised 42 non-diabetic RA patients, 42 diabetic RA patients and 42 controls. Intima media thickness (IMT) was measured in the common carotid and superficial femoral arteries. These vessels were screened for atherosclerotic plaque. Results: Plaque was more prevalent in diabetic RA patients than in non-diabetic RA patients or controls. Carotid IMT and femoral IMT were higher in diabetic RA patients compared to controls. So was femoral IMT in diabetic compared to non-diabetic RA patients. The prevalence of increased IMT and plaque was comparable in carotid ultrasonography and combined carotid and femoral ultrasonography in all groups. Conclusions: Subclinical atherosclerosis was found to be higher in diabetic RA patients than in non-diabetic RA patients. The combination of carotid and femoral artery ultrasonography did not improve the detection of atherosclerosis in RA.
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Affiliation(s)
- Bartłomiej Kisiel
- Bartłomiej Kisiel, MD, PhD, Department of Internal Diseases and Rheumatology, Military Institute of Medicine, Warszawa, Poland
| | - Robert Kruszewski
- Robert Kruszewski, MD, Department of Internal Diseases and Rheumatology, Military Institute of Medicine, Warszawa, Poland
| | - Aleksandra Juszkiewicz
- Aleksandra Juszkiewicz, MD, PhD. Department of Internal Diseases and Rheumatology, Military Institute of Medicine, Warszawa, Poland
| | - Krzysztof Kłos
- Krzysztof Kłos, MD, PhD. Department of Infectious Diseases and Allergology, Military Institute of Medicine, Warszawa, Poland
| | - Małgorzata Tłustochowicz
- Małgorzata Tłustochowicz, MD, PhD. Department of Internal Diseases and Rheumatology, Military Institute of Medicine, Warszawa, Poland
| | - Witold Tłustochowicz
- Witold Tłustochowicz, MD, PhD. Department of Internal Diseases and Rheumatology, Military Institute of Medicine, Warszawa, Poland
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Di Minno MND, Ambrosino P, Lupoli R, Di Minno A, Tasso M, Peluso R, Tremoli E. Clinical assessment of endothelial function in patients with rheumatoid arthritis: A meta-analysis of literature studies. Eur J Intern Med 2015; 26:835-42. [PMID: 26547241 DOI: 10.1016/j.ejim.2015.10.016] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Revised: 07/27/2015] [Accepted: 10/21/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Several studies reported an increased cardiovascular (CV) morbidity and mortality in patients with rheumatoid arthritis (RA). Flow-mediated (FMD) and nitrate-mediated dilation (NMD) are considered non-invasive methods to assess endothelial function and surrogate markers of subclinical atherosclerosis. METHODS We performed a systematic review with meta-analysis and meta-regression of literature studies evaluating the impact of RA on FMD and NMD. Studies evaluating the relationship between RA and markers of CV risk (FMD and NMD) were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. The random-effect method was used for analyses and results were expressed as mean difference (MD). RESULTS A total of 20 studies (852 RA patients, 836 controls) were included in the final analysis. In detail, 20 studies with data on FMD (852 cases, 836 controls) and 5 studies with data on NMD (207 cases, 147 controls) were analyzed. Compared to controls, RA patients showed a significantly lower FMD (MD: -2.16%; 95% CI: -3.33, -0.98; P=0.0003), with no differences in NMD (MD: -0.41%; 95% CI: -2.89, 2.06; P=0.74). Interestingly, a lower FMD (MD: -2.00%; 95% CI: -3.20, -0.80; P=0.001) and no differences in NMD (P=0.49) were confirmed when excluding data on patients with early-RA. Meta-regression models showed that a more severe inflammatory status was associated with a more significant impairment in FMD. CONCLUSIONS RA patients show impaired FMD, which is currently considered an independent predictor of CV events. The presence of endothelial dysfunction in RA should be taken into account to plan adequate prevention strategies and therapeutic approaches.
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Affiliation(s)
- Matteo Nicola Dario Di Minno
- Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
| | - Pasquale Ambrosino
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Roberta Lupoli
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Alessandro Di Minno
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Marco Tasso
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Rosario Peluso
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Elena Tremoli
- Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy
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Wang P, Guan SY, Xu SZ, Li HM, Leng RX, Li XP, Pan HF. Increased carotid intima-media thickness in rheumatoid arthritis: an update meta-analysis. Clin Rheumatol 2015; 35:315-23. [PMID: 26614535 DOI: 10.1007/s10067-015-3130-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Revised: 10/20/2015] [Accepted: 11/22/2015] [Indexed: 12/14/2022]
Abstract
This study aims to derive a more precise estimation on carotid intima-media thickness (CIMT) level in patients with rheumatoid arthritis (RA) and related factors. Studies published from January 1, 1982 to December 31, 2014 in English, which comparing CIMT between RA group and control group were searched in PubMed, Embase, and Cochrane Library databases. Heterogeneity test was performed, and publication bias was evaluated. Stata software 12.0 was used to perform the meta-analysis. Two-thousand one hundred sixty-three articles were obtained after searching databases, and 47 studies were finally included in the meta-analysis. The result of the analysis in random effect model showed that RA group had significantly higher CIMT than control group, with the standardized mean difference (SMD) of 1.04 and 95% CI (0.81,1.27). To evaluate the stability of our results, sensitivity analyses were performed, and the results showed no significant change when any one study was excluded. Subgroup analyses showed that region, race, age, BMI, and disease duration were associated with CIMT in RA patients. In summary, CIMT in RA patients is thicker than healthy controls, and it is influenced by region, race, age, BMI, and disease duration.
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Affiliation(s)
- Peng Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, People's Republic of China.,Anhui provincial laboratory of population health and major disease screening and diagnosis, Anhui, 230032, People's Republic of China
| | - Shi-Yang Guan
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, People's Republic of China.,Anhui provincial laboratory of population health and major disease screening and diagnosis, Anhui, 230032, People's Republic of China
| | - Shu-Zhen Xu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, People's Republic of China.,Anhui provincial laboratory of population health and major disease screening and diagnosis, Anhui, 230032, People's Republic of China
| | - Hong-Miao Li
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, People's Republic of China.,Anhui provincial laboratory of population health and major disease screening and diagnosis, Anhui, 230032, People's Republic of China
| | - Rui-Xue Leng
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, People's Republic of China.,Anhui provincial laboratory of population health and major disease screening and diagnosis, Anhui, 230032, People's Republic of China
| | - Xiang-Pei Li
- Department of Rheumatology, Anhui Provincial Hospital, Hefei, China
| | - Hai-Feng Pan
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, People's Republic of China. .,Anhui provincial laboratory of population health and major disease screening and diagnosis, Anhui, 230032, People's Republic of China.
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Manrique-Arija S, Ureña I, Valdivielso P, Rioja J, Jiménez-Núñez FG, Irigoyen MV, Fernández-Nebro A. Insulin resistance and levels of adipokines in patients with untreated early rheumatoid arthritis. Clin Rheumatol 2015; 35:43-53. [PMID: 26526677 PMCID: PMC4710654 DOI: 10.1007/s10067-015-3106-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2015] [Revised: 10/03/2015] [Accepted: 10/21/2015] [Indexed: 01/02/2023]
Abstract
The aim of this study is to investigate the presence of insulin resistance (IR) in patients with untreated early rheumatoid arthritis (ERA) and its relationship with adipokines, inflammatory cytokines, and treatment. In this prospective study, we enrolled 46 ERA patients with a disease duration of <1 year, and 45 sex-, age-, race-, and body mass index (BMI)-matched controls. Patients and controls with diabetes or a history of glucocorticoid (GC) or disease-modifying antirheumatic drugs (DMARDs) use were excluded. Patients were assessed at the time of diagnosis (visit 1) and after 6 months of treatment (visit 2). The main outcomes were homeostatic model assessment of IR (HOMA-IR) and β-cell function (HOMA-β) and quantitative insulin sensitivity check index (QUICKI). A multivariate regression analysis was performed to analyze IR adjusting according to lipids, body composition, physical activity, nutrition, and inflammatory cytokine and adipokine levels. The baseline HOMA-IR, HOMA-β, and QUICKI values were similar in both groups. However, patients showed lower levels of physical activity, total cholesterol, and high-density lipoprotein. Moreover, the inflammatory cytokines and resistin concentrations were higher in patients than controls. Multivariate analysis indicated that BMI and baseline rheumatoid factor levels were positively associated with HOMA-IR and HOMA-β, and negatively with QUICKI. After DMARD treatment, patients showed improvements in inflammatory parameters and lipids whereas IR remained stable. Furthermore, adiponectin and resistin concentrations decreased slightly. Our data suggest that IR is not present in ERA patients either at diagnosis or at 6 months after treatment. However, symptom duration and fat mass appear to be related.
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Affiliation(s)
- Sara Manrique-Arija
- UGC de Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain
| | - Inmaculada Ureña
- UGC de Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain
| | - Pedro Valdivielso
- UGC de Medicina Interna, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain
| | - José Rioja
- Departamento de Medicina y Dermatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain
| | - Francisco G Jiménez-Núñez
- UGC de Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain
| | - María V Irigoyen
- UGC de Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain
| | - Antonio Fernández-Nebro
- UGC de Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
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de Oliveira BMGB, Medeiros MMDC, de Cerqueira JVM, de Souza Quixadá RT, de Oliveira ÍMX. Metabolic syndrome in patients with rheumatoid arthritis followed at a University Hospital in Northeastern Brazil. REVISTA BRASILEIRA DE REUMATOLOGIA 2015; 56:117-25. [PMID: 27267524 DOI: 10.1016/j.rbre.2015.08.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Accepted: 05/29/2015] [Indexed: 11/30/2022] Open
Abstract
INTRODUCTION Patients with rheumatoid arthritis (RA) are 30-60% more likely to develop cardiovascular disease (CV) than the general population. Metabolic syndrome (MS), defined by a number of cardiovascular risk factors, confers a greater risk of CVdisease and diabetes. The association of MS with RA is not yet fully understood and its prevalence varies from 19 to 63% across studies. OBJECTIVES To assess the prevalence of MS in a population of RA patients followed in a hospital in Northeastern Brazil and analyze associations of demographic and clinical factors with MS. METHODS Outpatients with RA were evaluated in a cross-sectional study regarding demographic, clinical, laboratory and anthropometric data. The criteria for defining MS were those adopted by NCEPIII (2005) and IDF (2006). RESULTS 110 patients with RA were studied; 97.3% were female, with a mean age of 55.5 years (SD=12.9) and duration of illness of 11.2 years (SD=7.3). The MS prevalence from NCEPIII (2005) and IDF (2005) were, respectively, 50% and 53.4%. Advanced age (57.9±11.9 versus 52.9±13.5; p=0.04) and smoking load >20 packs/year (29% versus 9%, p=0.008) were associated with MS. The major components of the metabolic syndrome were abdominal obesity (98.1%), hypertension (80%) and low HDL cholesterol (72.2%). CONCLUSIONS RA patients in a tertiary center in Northeastern Brazil showed high prevalence of MS. It is worth noting that almost all patients had MS and abdominal obesity, which has important practical implications. In addition to the components of MS, age and smoking were associated with this syndrome.
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Burska AN, Sakthiswary R, Sattar N. Effects of Tumour Necrosis Factor Antagonists on Insulin Sensitivity/Resistance in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. PLoS One 2015; 10:e0128889. [PMID: 26110878 PMCID: PMC4482317 DOI: 10.1371/journal.pone.0128889] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Accepted: 05/02/2015] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE Beyond the joints, TNFi (tumour necrosis factor inhibitor) therapy may confer systemic benefits in rheumatoid arthritis (RA). Several studies have investigated the role of TNFi on insulin resistance/sensitivity (IR/IS). This question is of general interest given the emerging evidence linking inflammation and insulin resistance. The main aim of this review was to summarise the published data and to determine the effects of TNFi on IR/IS. METHODS We searched the PubMed and ISI Web of Knowledge databases for studies which examined the effects of TNFi on IR/IS. The studies were assessed independently by two reviewers according to a pre-specified protocol. The data on Homeostatic Model Assessment for Insulin resistance (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI) were pooled and reported as standard difference in means (SDM) with 95% confidence interval (CI) using a random-effects model. RESULTS A total of eight studies with 260 subjects met the selection criteria. The duration of the studies was from 8 weeks to 12 months. There was statistically significant reduction in HOMA index in six out of eight studies and four reported significant increment in QUICKI. The pooled analysis revealed significant reduction in HOMA [SDM-0.148, 95%CI[-0.278 to -0.017], p=0.026] and increment in QUICKI [SDM 0.312, 95%CI[0.019 to 0.606], p=0.037] with TNFi. CONCLUSION There is emerging evidence to support that TNFi therapy improves IS and reduces IR in RA. Further, well conducted trials are needed to determine if such effects translate to lower incidence of diabetes in RA or other autoimmune conditions on biologic therapy.
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Affiliation(s)
- Agata N. Burska
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom
| | | | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom
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Giles JT, Danielides S, Szklo M, Post WS, Blumenthal RS, Petri M, Schreiner PJ, Budoff M, Detrano R, Bathon JM. Insulin resistance in rheumatoid arthritis: disease-related indicators and associations with the presence and progression of subclinical atherosclerosis. Arthritis Rheumatol 2015; 67:626-36. [PMID: 25504899 DOI: 10.1002/art.38986] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2014] [Accepted: 12/02/2014] [Indexed: 01/04/2023]
Abstract
OBJECTIVE Systemic inflammation and insulin resistance (IR) are linked, yet the determinants of IR and its impact on atherosclerosis in rheumatoid arthritis (RA) are incompletely understood. The aim of this study was to explore the prevalence of IR in RA and non-RA populations and investigate whether the associations of IR with measures of atherosclerosis differ between these groups. METHODS IR was quantified using the homeostatic model assessment of IR (HOMA-IR), and was compared between RA patients and demographically matched non-RA controls. Differences in the associations between the HOMA-IR index and the Agatston coronary artery calcium (CAC) score, ultrasound-determined intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA), and focal plaque in the ICA/carotid bulb were compared according to RA status. RESULTS Among the 195 RA patients and 198 controls studied, average HOMA-IR levels were higher in the RA group by 31%, and were consistently higher in the RA group regardless of stratification by demographic or cardiometabolic risk factors. While the HOMA-IR index was strongly and significantly associated with C-reactive protein (CRP) and interleukin-6 (IL-6) levels in the control group, the association was weaker in the RA group. Among RA patients, higher HOMA-IR levels were associated with rheumatoid factor (RF) seropositivity in men and women, and prednisone use in women only. Before adjustment, higher HOMA-IR levels were associated with all assessed measures of subclinical atherosclerosis in the control group only; associations were diminished and lost statistical significance after adjustment for cardiovascular risk factors. Among the RA patients, neither baseline nor average HOMA-IR levels were significantly associated with change in any of the atherosclerosis measures over an average of 3.2 years of followup. CONCLUSION Although IR was higher in RA patients than in non-RA controls, higher levels may not independently impart additional risk of atherosclerosis.
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Skeoch S, Bruce IN. Atherosclerosis in rheumatoid arthritis: is it all about inflammation? Nat Rev Rheumatol 2015; 11:390-400. [PMID: 25825281 DOI: 10.1038/nrrheum.2015.40] [Citation(s) in RCA: 217] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Rheumatoid arthritis (RA) has long been associated with increased cardiovascular risk, but despite substantial improvements in disease management, mortality remains high. Atherosclerosis is more prevalent in RA than in the general population, and atherosclerotic lesions progress at a faster rate and might be more prone to rupture, causing clinical events. Cells and cytokines implicated in RA pathogenesis are also involved in the development and progression of atherosclerosis, which is generally recognized as an inflammatory condition. The two diseases also share genetic and environmental risk factors, which suggests that patients who develop RA might also be predisposed to developing cardiovascular disease. In RA, inflammation and atherosclerosis are closely linked. Inflammation mediates its effects on atherosclerosis both through modulation of traditional risk factors and by directly affecting the vessel wall. Treatments such as TNF inhibitors might have a beneficial effect on cardiovascular risk. However, whether this benefit is attributable to effective control of inflammation or whether targeting specific cytokines, implicated in atherosclerosis, provides additional risk reduction is unclear. Further knowledge of the predictors of cardiovascular risk, the effects of early control of inflammation and of drug-specific effects are likely to improve the recognition and management of cardiovascular risk in patients with RA.
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Affiliation(s)
- Sarah Skeoch
- Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester Academic Health Science Centre, Brunswick Street, Manchester M13 9PL, UK
| | - Ian N Bruce
- NIHR Manchester Musculoskeletal Biomedical Research Unit, and Kellgren Centre for Rheumatology, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK
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Parra-Salcedo F, Contreras-Yáñez I, Elías-López D, Aguilar-Salinas CA, Pascual-Ramos V. Prevalence, incidence and characteristics of the metabolic syndrome (MetS) in a cohort of Mexican Mestizo early rheumatoid arthritis patients treated with conventional disease modifying anti-rheumatic drugs: the complex relationship between MetS and disease activity. Arthritis Res Ther 2015; 17:34. [PMID: 25889060 PMCID: PMC4362822 DOI: 10.1186/s13075-015-0549-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2014] [Accepted: 02/03/2015] [Indexed: 12/13/2022] Open
Abstract
Introduction A higher prevalence of metabolic syndrome (MetS) has been described in rheumatoid arthritis (RA), along with an association with disease activity. Objectives were to describe prevalence of MetS at RA diagnosis in a cohort of Mexican Mestizo early RA patients, and to define a causal association between MetS and disease activity. Methods The study population was a prospective cohort. At baseline and at fixed 6-months-intervals, patients had medical evaluations, fasting serum glucose, triglycerides, high-density lipoprotein cholesterol and acute reactant-phase determinations. MetS was defined according to international criteria and body mass index (BMI) ≥30 kg/m2 was used as a surrogate of the waist circumference. The study was approved by the internal review board. Appropriated statistics and Cox regression analysis were used. All statistical tests were two-sided and evaluated at the 0.05 significance level. Results Up to March 2014, data from 160 patients were analyzed. At baseline, they were more frequently middle-aged females and had moderate to high disease activity. Prevalence of MetS varied from 11.3% to 17.5% in patients and was lower to that from matched controls (versus 26.3% to 30%, P ≤0.01). Up to last follow-up, 39 patients (34.5%) developed incidental MetS. In the Cox regression analysis, cumulative disease activity score (DAS) 28 (odds ratio (OR): 1.81, 95% confidence interval (CI): 1.346 to 2.433, P = 0.000) and baseline BMI (OR: 1.13, 96% CI: 1.035 to 1.236, P = 0.007) were the only predictors for incidental MetS. RA patients with incidental MetS accumulated more disease activity and had less frequent remission than their counterparts. Logistic regression analysis showed that incidental MetS (OR: 0.2, 95% CI: 0.01 to 0.99, P = 0.052) and baseline DAS28 (OR: 0.4, 95% CI: 0.2 to 0.9, P = 0.02) were the only predictors for achieving or maintaining sustained (≥6 months) remission. Conclusions MetS prevalence in a cohort of early RA patients was lower than that from matched controls. Cumulative disease activity and higher BMI were risk factors for incidental Mets; higher baseline disease activity and incidental MetS prevented sustained remission. In addition to disease activity, MetS needs to be controlled to impact disease outcomes.
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Affiliation(s)
- Federico Parra-Salcedo
- Department of Rheumatology and Immunology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, colonia sección XVI, Tlalpan 14000, México, DF, México.
| | - Irazú Contreras-Yáñez
- Department of Rheumatology and Immunology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, colonia sección XVI, Tlalpan 14000, México, DF, México.
| | - Daniel Elías-López
- Department of Metabolism and Endocrinology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, colonia sección XVI, Tlalpan 14000, México, DF, México.
| | - Carlos A Aguilar-Salinas
- Department of Metabolism and Endocrinology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, colonia sección XVI, Tlalpan 14000, México, DF, México.
| | - Virginia Pascual-Ramos
- Department of Rheumatology and Immunology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, colonia sección XVI, Tlalpan 14000, México, DF, México.
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Elshereef RR, Darwish A, Ali A, Abdel-kadar M, Hamdy L. Asymptomatic atherosclerosis in egyptian rheumatoid arthritis patients and its relation to disease activity. Int J Rheumatol 2015; 2015:381931. [PMID: 25737726 PMCID: PMC4337266 DOI: 10.1155/2015/381931] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2014] [Revised: 01/06/2015] [Accepted: 01/11/2015] [Indexed: 02/03/2023] Open
Abstract
Aim. To detect the frequency of subclinical atherosclerosis in rheumatoid arthritis patients without clinically evident atherosclerosis and to correlate its presence with the disease activity. Patients and Methods. Our study includes 112 RA patients (group 1) and 40 healthy controls (group 11). All patients and controls were subjected to full history taking, clinical examination, and laboratory investigations. Carotid intima media wall thickness (IMT) and carotid plaques were measured in both groups by B-mode ultrasonography; also color duplex Doppler ultrasound of the brachial artery was done to detect endothelial function. Results. There is atherosclerosis in 31.3% of asymptomatic RA patients compared with only 5% in controls (P = 0.003(**)). A significant difference was detected in patients with and without atherosclerosis regarding duration of the disease (P = 0.0001(***)) and patient's age (P = 0.01(*)). There is highly statistical significant correlation between atherosclerosis and disease activity index. Conclusion. The frequency of subclinical atherosclerosis was high in long-term active RA patients.
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Affiliation(s)
- Rawhya R. Elshereef
- Rheumatology and Rehabilitation Department, Minia University, P.O. Box 61519, Minia 61111, Egypt
| | - Aymen Darwish
- Rheumatology and Rehabilitation Department, Minia University, P.O. Box 61519, Minia 61111, Egypt
| | - Amal Ali
- Rheumatology and Rehabilitation Department, Minia University, P.O. Box 61519, Minia 61111, Egypt
| | | | - Lamiaa Hamdy
- Clinical Pathology Department, Minia University, P.O. Box 61519, Minia 61111, Egypt
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Ambrosino P, Tasso M, Lupoli R, Di Minno A, Baldassarre D, Tremoli E, Di Minno MND. Non-invasive assessment of arterial stiffness in patients with rheumatoid arthritis: a systematic review and meta-analysis of literature studies. Ann Med 2015; 47:457-67. [PMID: 26340234 DOI: 10.3109/07853890.2015.1068950] [Citation(s) in RCA: 74] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION Patients with rheumatoid arthritis (RA) have an increased cardiovascular (CV) morbidity and mortality. Pulse-wave velocity (PWV) and augmentation index (AIx) are non-invasive methods to assess arterial stiffness, a marker of CV risk. We performed a meta-analysis evaluating the impact of RA on aortic-PWV, brachial-PWV, brachial-ankle (ba-) PWV, AIx, and AIx normalized to a 75 beats/minute heart rate (AIx@75). MATERIALS AND METHODS Studies evaluating the relationship between RA and aortic-PWV, brachial-PWV, ba-PWV, AIx, and AIx@75 were systematically searched. A total of 25 studies (1,472 RA patients, 1,583 controls) were included. RESULTS Compared to controls, RA patients showed a significantly higher aortic-PWV (mean difference 1.32 m/s; 95% CI 0.77, 1.88; P < 0.00001), ba-PWV (MD 198.42 cm/s; 95% CI 45.79, 342.76; P = 0.01), AIx (MD 11.50%; 95% CI 5.15, 17.86; P = 0.0004), and AIx@75 (MD 6.99%; 95% CI 4.92, 9.06; P < 0.00001), with a trend toward a higher brachial-PWV (MD 0.34 m/s; 95% CI -0.03, 0.70; P = 0.07). When analyzing studies on early RA, the difference in aortic-PWV among RA patients and controls was even higher (MD 2.30 m/s; 95% CI 1.15, 3.45; P < 0.0001). CONCLUSION Meta-regression showed that a more severe inflammatory status impacted on aortic-PWV, AIx, and AIx@75. Arterial stiffness, a recognized marker of CV risk, is increased in RA patients. This alteration is associated with the severity of the inflammatory status and is present even in early-stage disease.
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Affiliation(s)
- Pasquale Ambrosino
- a Department of Clinical Medicine and Surgery , Federico II University , Naples , Italy
| | - Marco Tasso
- a Department of Clinical Medicine and Surgery , Federico II University , Naples , Italy
| | - Roberta Lupoli
- a Department of Clinical Medicine and Surgery , Federico II University , Naples , Italy
| | | | | | - Elena Tremoli
- b Centro Cardiologico Monzino, IRCCS , Milan , Italy
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Zhao H, Liu S, Long M, Peng L, Deng H, You Y. Arg972insulin receptor substrate-1 polymorphism and risk and severity of rheumatoid arthritis. Int J Rheum Dis 2014; 19:141-5. [PMID: 25424426 DOI: 10.1111/1756-185x.12366] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Hongjun Zhao
- Department of Rheumatology and Immunology; Xiangya Hospital; Central South University; Changsha China
| | - Shiqing Liu
- Department of Rheumatology and Immunology; Xiangya Hospital; Central South University; Changsha China
| | - Mei Long
- Department of Rheumatology and Immunology; Xiangya Hospital; Central South University; Changsha China
| | - Lijuan Peng
- Department of Rheumatology and Immunology; Xiangya Hospital; Central South University; Changsha China
| | - Hongxiang Deng
- Department of Rheumatology and Immunology; Xiangya Hospital; Central South University; Changsha China
| | - Yunhui You
- Department of Rheumatology and Immunology; Xiangya Hospital; Central South University; Changsha China
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