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El Hajji F, Hakkou Z, Al-Qaaneh AM, Youssoufi MH, Evariste Akissi ZL, Sahpaz S, Alla C, Zahi A, Abid S, Shityakov S, Ziyyat A, Mekhfi H, Bnouham M, Legssyer A. Preliminary assessment of cardiovascular effects and chemoinformatic analysis of total aqueous extract and fractions from Inula viscosa leaves. J Mol Histol 2025; 56:134. [PMID: 40244355 DOI: 10.1007/s10735-025-10408-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 03/21/2025] [Indexed: 04/18/2025]
Abstract
Inula viscosa (L.) Aiton [Dittrichia viscosa (L.) Greuter] (Asteraceae) is an evergreen perennial herb that grows in different regions of the Mediterranean Basin. It has been particularly used for the treatment of hypertension and diabetes in the Eastern and South-East regions of Morocco. To assess the cardiovascular effects of total aqueous extract and various fractions of Inula viscosa leaves in rat-isolated hearts and aortic rings, and to investigate the potential mechanisms of action of the most active extract(s). In Langendorff's isolated heart system, heart rate (HR) and left ventricular developed pressure (LVDP) were measured for three increasing concentrations of TAE, DCMF, EAF, BF, and AF (0.003, 0.03, and 0.3 mg/mL). Propranolol (1.5 × 10⁻5 M) and Verapamil (2 × 10⁻7 M) were used to investigate the potential mechanisms of action of both EAF and BF. In isolated intact aortic rings, four cumulative concentrations of EAF and BF (0.0001, 0.001, 0.01, and 1 mg/mL) were tested for their vasorelaxant effects. The role of the endothelium in the vasorelaxant effect of EAF was examined by denuding aortic rings. To explore the involvement of the nitric oxide (NO) pathway, β-adrenergic receptors, calcium channels, and the sarco/endoplasmic reticulum Ca2⁺-ATPase (SERCA) pump, intact aortic rings were preincubated with L-NAME (10⁻4 M), Propranolol hydrochloride (10⁻6 M), Verapamil hydrochloride (10⁻5 M), and Thapsigargin (10⁻7 M), respectively. The hypotensive effects of both BF (125 mg/kg) and EAF (125 mg/kg) were evaluated indirectly using the tail-cuff method in normotensive rats. Additionally, the antioxidant activity, as well as the total phenolic and flavonoid contents of all prepared extracts, were determined. To further investigate the antioxidant properties, computational analysis was conducted to determine the bond dissociation energies of the hydroxyl groups on the B-ring of luteolin and quercetin, which are present in EAF and BF, respectively. Finally, an UHPLC analysis was performed for BF. In isolated perfused hearts, TAE induced a dose-dependent positive inotropic effect, accompanied by mild bradycardia. EAF exhibited both positive inotropic and chronotropic effects in a concentration-dependent manner. BF demonstrated a highly dose-dependent, selective positive inotropic effect (LVDP = 76.5 ± 19.2% vs. control at 0.3 mg/mL) with no significant impact on HR. Our findings suggest that BF acts independently of β-adrenoreceptor-dependent pathways, whereas EAF may exert its effects through β-agonistic activity. Additionally, Ca2⁺ channels may play a role in the effects of both fractions. In phenylephrine-precontracted thoracic arteries, both BF and EAF induced concentration-dependent vasorelaxation, with EAF producing the most potent vasorelaxant effect (Emax = 84.16 ± 3.68%). EAF mediates an endothelium-independent vasodilatory response through inhibition of voltage-dependent Ca2⁺ channels and activation of the SERCA pump. BF also demonstrated a significant hypotensive effect in vivo. Among the various extracts, BF contained the highest total phenolic and flavonoid contents and exhibited the strongest DPPH scavenging activity (IC50 = 7.13 µg/mL). Molecular docking studies supported these findings, indicating that quercetin is more effective at scavenging free radicals than luteolin. Phytochemical study of BF revealed the presence of phenolic compounds such as chlorogenic acid, three isochlorogenic acids (A, B and C), tri-caffeoylhexaric acid, methyl 3,5-dicaffeoylquinic acid, quercetin-3-glucuronide and the new molecule 1,3,4,5-tetracaffeoylaltraric acid. This study revealed a novel and potent selective inotropic effect of the BF fraction from I. viscosa leaves, characterized by the absence of tachycardia and independence from β-adrenergic receptors in isolated rat hearts.
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Affiliation(s)
- Fatima El Hajji
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology, and Health, Faculty of Sciences, Mohammed First University, Oujda, Morocco
| | - Zineb Hakkou
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology, and Health, Faculty of Sciences, Mohammed First University, Oujda, Morocco
- Higher Institute of Nursing Professions and Health Techniques, 60000, Oujda, Morocco
| | - Ayman M Al-Qaaneh
- Faculty of Allied Medical Sciences, Al-Balqa Applied University (BAU), Al-Salt, 19117, Jordan.
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology (JUST), Irbid, 22110, Jordan.
| | - Moulay Hfid Youssoufi
- Laboratory of Applied Chemistry and Environment, Faculty of Sciences, Mohammed First University, Oujda, Morocco
| | - Zachee Louis Evariste Akissi
- BioEcoAgro Joint Cross-Border Research Unit, UMRt 1158, Univ. Lille, Univ. Liège, UPJV, JUNIA, Univ. Artois, Univ. Littoral Côte d'Opale, Cité Scientifique, 59655, Villeneuve d'Ascq, France
| | - Sevser Sahpaz
- BioEcoAgro Joint Cross-Border Research Unit, UMRt 1158, Univ. Lille, Univ. Liège, UPJV, JUNIA, Univ. Artois, Univ. Littoral Côte d'Opale, Cité Scientifique, 59655, Villeneuve d'Ascq, France
| | - Chaimae Alla
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology, and Health, Faculty of Sciences, Mohammed First University, Oujda, Morocco
| | - Amal Zahi
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology, and Health, Faculty of Sciences, Mohammed First University, Oujda, Morocco
| | - Sanae Abid
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology, and Health, Faculty of Sciences, Mohammed First University, Oujda, Morocco
| | - Sergey Shityakov
- Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany
| | - Abderrahim Ziyyat
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology, and Health, Faculty of Sciences, Mohammed First University, Oujda, Morocco
| | - Hassane Mekhfi
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology, and Health, Faculty of Sciences, Mohammed First University, Oujda, Morocco
| | - Mohamed Bnouham
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology, and Health, Faculty of Sciences, Mohammed First University, Oujda, Morocco
| | - Abdelkhaleq Legssyer
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology, and Health, Faculty of Sciences, Mohammed First University, Oujda, Morocco
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Liberale L, Tual-Chalot S, Sedej S, Ministrini S, Georgiopoulos G, Grunewald M, Bäck M, Bochaton-Piallat ML, Boon RA, Ramos GC, de Winther MPJ, Drosatos K, Evans PC, Ferguson JF, Forslund-Startceva SK, Goettsch C, Giacca M, Haendeler J, Kallikourdis M, Ketelhuth DFJ, Koenen RR, Lacolley P, Lutgens E, Maffia P, Miwa S, Monaco C, Montecucco F, Norata GD, Osto E, Richardson GD, Riksen NP, Soehnlein O, Spyridopoulos I, Van Linthout S, Vilahur G, Wentzel JJ, Andrés V, Badimon L, Benetos A, Binder CJ, Brandes RP, Crea F, Furman D, Gorbunova V, Guzik TJ, Hill JA, Lüscher TF, Mittelbrunn M, Nencioni A, Netea MG, Passos JF, Stamatelopoulos KS, Tavernarakis N, Ungvari Z, Wu JC, Kirkland JL, Camici GG, Dimmeler S, Kroemer G, Abdellatif M, Stellos K. Roadmap for alleviating the manifestations of ageing in the cardiovascular system. Nat Rev Cardiol 2025:10.1038/s41569-025-01130-5. [PMID: 39972009 DOI: 10.1038/s41569-025-01130-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/22/2025] [Indexed: 02/21/2025]
Abstract
Ageing of the cardiovascular system is associated with frailty and various life-threatening diseases. As global populations grow older, age-related conditions increasingly determine healthspan and lifespan. The circulatory system not only supplies nutrients and oxygen to all tissues of the human body and removes by-products but also builds the largest interorgan communication network, thereby serving as a gatekeeper for healthy ageing. Therefore, elucidating organ-specific and cell-specific ageing mechanisms that compromise circulatory system functions could have the potential to prevent or ameliorate age-related cardiovascular diseases. In support of this concept, emerging evidence suggests that targeting the circulatory system might restore organ function. In this Roadmap, we delve into the organ-specific and cell-specific mechanisms that underlie ageing-related changes in the cardiovascular system. We raise unanswered questions regarding the optimal design of clinical trials, in which markers of biological ageing in humans could be assessed. We provide guidance for the development of gerotherapeutics, which will rely on the technological progress of the diagnostic toolbox to measure residual risk in elderly individuals. A major challenge in the quest to discover interventions that delay age-related conditions in humans is to identify molecular switches that can delay the onset of ageing changes. To overcome this roadblock, future clinical trials need to provide evidence that gerotherapeutics directly affect one or several hallmarks of ageing in such a manner as to delay, prevent, alleviate or treat age-associated dysfunction and diseases.
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Affiliation(s)
- Luca Liberale
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Genoa, Italy
| | - Simon Tual-Chalot
- Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
| | - Simon Sedej
- Department of Cardiology, Medical University of Graz, Graz, Austria
| | - Stefano Ministrini
- Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland
| | | | - Myriam Grunewald
- Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Magnus Bäck
- Translational Cardiology, Centre for Molecular Medicine, Department of Medicine Solna, and Department of Cardiology, Heart and Vascular Centre, Karolinska Institutet, Stockholm, Sweden
- Inserm, DCAC, Université de Lorraine, Nancy, France
| | | | - Reinier A Boon
- Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC location VUmc, Amsterdam, Netherlands
| | - Gustavo Campos Ramos
- Department of Internal Medicine I/Comprehensive Heart Failure Centre, University Hospital Würzburg, Würzburg, Germany
| | - Menno P J de Winther
- Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences: Atherosclerosis and Ischaemic Syndromes; Amsterdam Infection and Immunity: Inflammatory Diseases, Amsterdam UMC location AMC, Amsterdam, Netherlands
| | - Konstantinos Drosatos
- Metabolic Biology Laboratory, Cardiovascular Center, Department of Pharmacology, Physiology, and Neurobiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Paul C Evans
- William Harvey Research Institute, Barts and The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Jane F Ferguson
- Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Sofia K Forslund-Startceva
- Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Claudia Goettsch
- Department of Internal Medicine I, Division of Cardiology, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Mauro Giacca
- British Heart foundation Centre of Reseach Excellence, King's College London, London, UK
| | - Judith Haendeler
- Cardiovascular Degeneration, Medical Faculty, University Hospital and Heinrich-Heine University, Düsseldorf, Germany
| | - Marinos Kallikourdis
- Adaptive Immunity Lab, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy
| | - Daniel F J Ketelhuth
- Cardiovascular and Renal Research Unit, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - Rory R Koenen
- CARIM-School for Cardiovascular Diseases, Department of Biochemistry, Maastricht University, Maastricht, Netherlands
| | | | - Esther Lutgens
- Department of Cardiovascular Medicine & Immunology, Mayo Clinic, Rochester, MN, USA
| | - Pasquale Maffia
- School of Infection & Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
| | - Satomi Miwa
- Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK
| | - Claudia Monaco
- Kennedy Institute, NDORMS, University of Oxford, Oxford, UK
| | - Fabrizio Montecucco
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Genoa, Italy
| | - Giuseppe Danilo Norata
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
| | - Elena Osto
- Division of Physiology and Pathophysiology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria
| | - Gavin D Richardson
- Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK
| | - Niels P Riksen
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands
| | - Oliver Soehnlein
- Institute of Experimental Pathology, University of Münster, Münster, Germany
| | - Ioakim Spyridopoulos
- Translational and Clinical Research Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK
| | - Sophie Van Linthout
- BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité - Universitätmedizin Berlin, Berlin, Germany
| | - Gemma Vilahur
- Research Institute, Hospital de la Santa Creu y Sant Pau l, IIB-Sant Pau, Barcelona, Spain
| | - Jolanda J Wentzel
- Cardiology, Biomedical Engineering, Erasmus MC, Rotterdam, Netherlands
| | - Vicente Andrés
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), CIBERCV, Madrid, Spain
| | - Lina Badimon
- Cardiovascular Health and Innovation Research Foundation (FICSI) and Cardiovascular Health and Network Medicine Department, University of Vic (UVIC-UCC), Barcelona, Spain
| | - Athanase Benetos
- Department of Geriatrics, University Hospital of Nancy and Inserm DCAC, Université de Lorraine, Nancy, France
| | - Christoph J Binder
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Ralf P Brandes
- Institute for Cardiovascular Physiology, Goethe University, Frankfurt am Main, Germany
| | - Filippo Crea
- Centre of Excellence of Cardiovascular Sciences, Ospedale Isola Tiberina - Gemelli Isola, Roma, Italy
| | - David Furman
- Buck Institute for Research on Aging, Novato, CA, USA
| | - Vera Gorbunova
- Departments of Biology and Medicine, University of Rochester, Rochester, NY, USA
| | - Tomasz J Guzik
- Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, UK
| | - Joseph A Hill
- University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Thomas F Lüscher
- Heart Division, Royal Brompton and Harefield Hospital and National Heart and Lung Institute, Imperial College, London, UK
| | - María Mittelbrunn
- Consejo Superior de Investigaciones Científicas (CSIC), Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid (UAM), Madrid, Spain
| | - Alessio Nencioni
- IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Genoa, Italy
- Dipartimento di Medicina Interna e Specialità Mediche-DIMI, Università degli Studi di Genova, Genova, Italy
| | - Mihai G Netea
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
| | - João F Passos
- Department of Physiology and Biomedical Engineering, Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA
| | - Kimon S Stamatelopoulos
- Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Nektarios Tavernarakis
- Medical School, University of Crete, and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, Greece
| | - Zoltan Ungvari
- Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Joseph C Wu
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA
| | - James L Kirkland
- Center for Advanced Gerotherapeutics, Division of Endocrinology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Giovanni G Camici
- Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland
| | - Stefanie Dimmeler
- Institute for Cardiovascular Regeneration, Goethe University, Frankfurt am Main, Germany
| | - Guido Kroemer
- Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université Paris Cité, Sorbonne Université, Inserm, Institut Universitaire de France, Paris, France
| | | | - Konstantinos Stellos
- Department of Cardiovascular Research, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
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Son WH, Jeong WM, Park IY, Ha MS. Enhancing Inflammatory Factors, Nitric Oxide, and Arterial Stiffness Through Aquatic Walking for Amelioration and Disease Prevention: Targeting in Obese Elderly Women. Mediators Inflamm 2024; 2024:5520987. [PMID: 39742290 PMCID: PMC11685319 DOI: 10.1155/mi/5520987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 11/13/2024] [Accepted: 12/04/2024] [Indexed: 01/03/2025] Open
Abstract
In elderly women, hormonal changes lead to elevated body fat content, which results in elevated levels of vascular inflammatory factors, thereby increasing the risk of cardiovascular diseases (CVDs) associated with endothelial dysfunction. Regular physical exercises tend to keep these in check and are protective to the body. Aerobic exercise has been reported to improve CVD in obese elderly women; in this regard, aquatic exercises have been demonstrated to be more efficient in energy metabolism than land-based exercise. This study aimed to examine the effect of aquatic walking exercises on the levels of inflammatory factors, nitric oxide (NO), and brachial-ankle pulse wave velocity (baPWV) in obese elderly women. We measured these in 26 obese elderly women who were randomly assigned to control (n = 12) and aquatic walking exercise (n = 14) groups. After subjecting them to aquatic walking exercises thrice a week for 12 weeks, we specifically found a significant reduction in IL-6 levels and an increase in NO levels in these obese elderly women. This was paralleled with a reduction in the right baPWV (baPWV-R). Together, these results indicate that aquatic walking exercises can help improve vascular inflammatory factors, NO levels, and arterial stiffness.
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Affiliation(s)
- Woo-Hyeon Son
- Institute of Convergence Bio-Health, Dong-A University, 26 Daesingongwon-ro, Seo-gu, Busan 49201, Republic of Korea
| | - Woo-Min Jeong
- Department of Sport and Leisure Studies, Gimcheon University, 214 Daehak-ro, Gimcheon-si, Gyeongsangbuk-do 39528, Republic of Korea
| | - In Young Park
- Undergraduate Liberal Arts College, Tongmyong University, 428 Sinseon-ro, Nam-gu, Busan 48520, Republic of Korea
| | - Min-Seong Ha
- Laboratory of Sports Conditioning: Nutrition Biochemistry and Neuroscience, Department of Sport Science, College of Arts and Sports, University of Seoul, 163 Seoulsiripdaero, Dongdaemun-gu, Seoul 02504, Republic of Korea
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Oakley SP, Stott S, Gill K, Weston L. Biomechanical determinants of rheumatoid arthritis severity and excess cardiovascular disease: common origins of two complex diseases. RMD Open 2024; 10:e004524. [PMID: 39578020 PMCID: PMC11590849 DOI: 10.1136/rmdopen-2024-004524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 10/20/2024] [Indexed: 11/24/2024] Open
Abstract
OBJECTIVES The determinants of rheumatoid arthritis (RA) severity and excess cardiovascular disease (CVD) are incompletely understood. Biomechanical factors are known to influence RA severity. Articular stiffness correlates with arterial and skin stiffness. This study explored the hypothesis that constitutional stiffness is a common determinant of RA severity and excess CVD. METHODS Fifty-eight patients with anti-CCP antibody (ACPA) positive RA and 57 controls were enrolled noting age, sex, body mass index, alcohol and tobacco exposure, Shared Epitope status and in RA disease duration, disease activity, ACPA titre and radiographic damage. Severe RA was defined as radiographic progression >1.3 mSharp points/year or requiring biological disease-modifying antirheumatic drugs (bDMARDs). Articular stiffness (Beighton Score and right 5th metacarpophalangeal (MCP) joint stress-strain responses), carotid-femoral pulse wave velocity and skin extensibility (percent increase distance two dots with manual traction dorsum right hand) were assessed. RESULTS Right 5th MCP stiffness correlated with Beighton Score and with arterial and skin stiffness. High radiographic rate was associated with greater MCP articular (t test p 0.014), arterial (p 0.044) and, in RA <5 years duration, greater skin stiffness (p 0.002) with similar trends in subjects requiring bDMARDs. In RA, arterial stiffness correlated with age (ß p<0.005), articular (ß p<0.001) and skin stiffness (ß p 0.037) and inversely with alcohol consumption (p 0.035). CONCLUSIONS Articular, arterial and skin stiffness correlated with each other and with RA severity. As skin is not affected by RA, this association suggests that constitutional stiffness might be a common determinant of RA and CVD. Prospective studies of at-risk preclinical and early RA are required to determine if this relationship is causal. TRIALS REGISTRATION NUMBER ACTRN12617000170325.
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Affiliation(s)
- Stephen Philip Oakley
- Rheumatology, Hunter New England Local Health District, New Lambton, New South Wales, Australia
- School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia
| | - Samantha Stott
- Radiology, Hunter New England Local Health District, New Lambton, New South Wales, Australia
- School of Medicine and Public Health, The University of Newcastle, Newcastle, New South Wales, Australia
| | - Kerri Gill
- Rheumatology, Hunter New England Local Health District, New Lambton, New South Wales, Australia
| | - Lyanne Weston
- Transplantation & Immunogenetics Service, Australian Red Cross Blood Service New South Wales and Australian Capital Territory, Alexandria, New South Wales, Australia
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Jia X, Yang Z, Li J, Mei Z, Jia L, Yan C. The impact of biologic agents on cardiovascular risk factors in patients with rheumatoid arthritis: A meta analysis. PLoS One 2024; 19:e0306513. [PMID: 39208032 PMCID: PMC11361434 DOI: 10.1371/journal.pone.0306513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Accepted: 06/19/2024] [Indexed: 09/04/2024] Open
Abstract
OBJECTIVE The purpose of the study is to evaluate the effects of biologic therapy on cardiovascular risk factors in rheumatoid arthritis patients to determine its clinical efficacy. METHODS Relevant literature was systematically searched in PubMed, Embase, and Cochrane Library databases. Meta-analysis was conducted using standardized mean differences (SMDs) and 95% confidence intervals (CIs) to evaluate cardiovascular risk factors and atherosclerosis. Heterogeneity, sensitivity analysis, and publication bias were assessed. Statistical significance was set at P<0.05. RESULTS The meta-analysis revealed that biologic treatment in RA patients was associated with decreased high-density lipoprotein cholesterol (HDL-C) levels compared to controls (MD: -0.10, 95% CI: [-0.14, -0.05], P<0.0001). Subgroup analysis based on treatment duration showed heterogeneity and a potential decrease in total cholesterol levels after 12 months of treatment (MD = -0.03, 95% CI [-0.21, -0.15], P = 0.76). Biologic therapy significantly reduced triglyceride levels compared to controls (MD = -0.23, 95% CI [-0.37, -0.09], P = 0.001), as observed in subgroup analysis. Moreover, biologics effectively decreased low-density lipoprotein cholesterol (LDL-C) levels (MD: -0.10, 95% CI: [-0.14, -0.05], P<0.0001). However, biologic treatment was associated with increased inner carotid artery thickness (MD: 0.05, 95% CI: [0.03, 0.07], P<0.0001), indicating potential adverse effects on cardiovascular health. No significant effect on pulse wave velocity (PWV) was observed (MD: -0.23, 95% CI: [-0.80, 0.34], P = 0.43, I2 = 0%, P = 0.55). CONCLUSION Biologic agents may improve lipid profiles in RA patients but could also have adverse effects on cardiovascular health. Further research is needed to comprehensively understand the impact of biologic therapy on lipid metabolism and cardiovascular outcomes in RA patients. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/PROSPERO/, CRD42024504911.
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Affiliation(s)
- Xiaodong Jia
- State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Zheming Yang
- State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning, China
| | - Jiayin Li
- State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning, China
| | - Zhu Mei
- State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning, China
| | - Lihui Jia
- State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Chenghui Yan
- State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
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Movassaghi S, Dormohammadi Toosi T, Aghayani S, Barkhori Mehni M, Najafi MT, Sadidi M. Investigating the Association of Aortic Stiffness and Phase Angle with the Clinical Course of Rheumatoid Arthritis. Adv Biomed Res 2024; 13:54. [PMID: 39411690 PMCID: PMC11478785 DOI: 10.4103/abr.abr_250_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 09/02/2023] [Accepted: 09/03/2023] [Indexed: 10/19/2024] Open
Abstract
Background Aortic stiffness is an independent predictor of cardiovascular events which is increased in rheumatoid arthritis (RA). It can be measured by carotid-femoral pulse wave velocity (cfPWV). Phase angle (PhA) is lower in patients with cardiovascular disease and may be informative in assessing the clinical course of RA. Materials and Methods In this observational and cross-sectional study, all RA patients referred to the Imam Khomeini Hospital rheumatology clinic between September 2022 and March 2023 were included in the study. RA activity was assessed using the DAS28 criteria. In the patients, PhA and cfPWV were measured using Inbody-s10 and PulsePen tonometer instruments. The relationships between PhA, cfPWV, clinical course of RA, and CRP were evaluated using regression analysis. Results 53 patients were included in the study (83% female, mean age 46.5 years). Significant inverse relationships existed between PhA, CRP, and age (P value = 0.003, 0.0001, R: 0.69, respectively). People with aortic stiffness had a lower mean PhA (P value = 0.05). In patients with RA duration of less than 10 years, the cfPWV percentile and the prevalence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) positive cases were higher than in patients with RA duration >10 years (P values = 0.02, 0.01, respectively). Conclusions With increasing duration of RA, aortic stiffness and positive serology cases decreased. PhA and cfPWV may be useful in assessing the clinical course of RA to prevent cardiovascular events.
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Affiliation(s)
- Shafieh Movassaghi
- Department of Rheumatology, Imam Khomeini Hospital Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Taraneh Dormohammadi Toosi
- Department of Rheumatology, Imam Khomeini Hospital Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Shila Aghayani
- Department of Rheumatology, Imam Khomeini Hospital Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahdi Barkhori Mehni
- Department of Radiology, School of Medicine, Kerman University of Medical Sciences, Tehran, Iran
| | - Mohammad Taghi Najafi
- Department of Nephrology, Imam Khomeini Hospital Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Nephrology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Sadidi
- Department of Rheumatology, Imam Khomeini Hospital Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Linde A, Gerdts E, Fevang BT, Eilertsen RK, Kringeland E, Alsing CL, Midtbø H. Factors associated with change in arterial stiffness in patients with rheumatoid arthritis: the JointHeart study. Blood Press 2024; 33:2353167. [PMID: 38824646 DOI: 10.1080/08037051.2024.2353167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 05/03/2024] [Indexed: 06/04/2024]
Abstract
BACKGROUND Rheumatoid arthritis (RA) predominantly affects women and is associated with hypertension and arterial stiffness. We explored factors associated with change in arterial stiffness in patients with RA treated with disease-modifying antirheumatic drug (DMARD) therapy. METHODS Seventy-seven outpatients with RA (age 55 ± 11, 69% women), with indication for treatment with biological or targeted synthetic DMARDs, were included. Pulse wave velocity (PWV), augmentation pressure (AP), augmentation index (AIx) and Disease Activity Score in 28 joints (DAS28) were measured at baseline and after a mean of 22 months of follow-up. RESULTS At follow-up, 83% used DMARDs and 73% had achieved remission or low disease activity. DAS28 decreased from 3.8 ± 1.3 to 2.8 ± 1.2 (p < 0.001). Mean PWV increased from 7.8 ± 1.6 m/s at baseline to 8.5 ± 1.8 m/s at follow-up (p < 0.001), while AP and AIx were stable. Increase in PWV during follow-up was associated with increase in systolic blood pressure (BP), diabetes, higher DAS28 and body mass index (BMI) at baseline, independent of achieved remission/low disease activity and use of DMARDs at follow-up. In multivariable analyses at follow-up, female sex was associated with higher AP and AIx, but with lower PWV, after adjusting for possible confounders. CONCLUSION In patients with RA, higher disease activity, BMI and diabetes at baseline, together with increase in office systolic BP were associated with an increase in arterial stiffness during follow-up, despite DMARD therapy. This highlights the need for management of cardiovascular risk factors in addition to reducing the inflammatory load in patients with RA to preserve arterial function.
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Affiliation(s)
- Anja Linde
- Department of Clinical Science, Centre for Research on Cardiac Disease in Women, University of Bergen, Bergen, Norway
- Norwegian Research Centre for Women's Health, Oslo University Hospital, Oslo, Norway
| | - Eva Gerdts
- Department of Clinical Science, Centre for Research on Cardiac Disease in Women, University of Bergen, Bergen, Norway
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
| | - Bjørg T Fevang
- Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
| | - Rune K Eilertsen
- Department of Clinical Science, Centre for Research on Cardiac Disease in Women, University of Bergen, Bergen, Norway
- Department of Cardiology, Stavanger University Hospital, Stavanger, Norway
| | - Ester Kringeland
- Department of Clinical Science, Centre for Research on Cardiac Disease in Women, University of Bergen, Bergen, Norway
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
| | - Christian L Alsing
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
- Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Helga Midtbø
- Department of Clinical Science, Centre for Research on Cardiac Disease in Women, University of Bergen, Bergen, Norway
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
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Gasparotto M, Di Pierro G, Toffoli B, Grillo A, Bressan M, Fiorentin M, Di Luozzo L, Fischetti F, Zen M, Fabris B, Bernardi S, Tomietto P. Preliminary Study on Pulse Wave Changes in Patients with Inflammatory Arthropathies Treated with bDMARDs. J Clin Med 2024; 13:2684. [PMID: 38731213 PMCID: PMC11084438 DOI: 10.3390/jcm13092684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 04/23/2024] [Accepted: 04/29/2024] [Indexed: 05/13/2024] Open
Abstract
Background: Patients with inflammatory arthropathies exhibit an increased cardiovascular disease (CVD) risk as compared to the general population, which is not fully quantified by the conventional CVD risk scores. Biotechnological disease-modifying drugs (bDMARDs) have proved beneficial to reduce the overall CVD risk in these patients, although CVD remains a major cause of increased mortality. Since it has been shown that pulse wave parameters and in particular carotid-femoral pulse wave velocity (cfPWV) are predictors of CVD risk, the aim of this study was to evaluate their changes in patients with inflammatory arthropathies before and after bDMARD therapy. Methods: Pulse wave parameters were evaluated with applanation tonometry in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), and rheumatoid arthritis (RA), before and after two years of bDMARD therapy. Results: At baseline, cfPWV was significantly associated with age (p < 0.001) and, among pulse wave parameters, the subendocardial viability ratio was negatively associated with C-reactive protein (CRP) (p = 0.04) and the HAQ-disability index (p = 0.03). At baseline, PsA patients showed a higher percentage of male subjects, higher CRP, and the highest cfPWV values (p = 0.048). After two years, pulse wave parameters improved in the AS and RA groups, but not in the PsA group. Conclusions: Our data confirm that pulse wave parameters are potentially reversible after bDMARD therapy, as they improved in AS and RA patients. In PsA patients, there were no changes, which may be due to the higher percentage of male subjects and higher baseline cfPWV values.
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Affiliation(s)
- Michela Gasparotto
- UCO Medicina Clinica, ASUGI, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (M.G.); (A.G.); (F.F.) (B.F.); (P.T.)
- Department of Medicine, Padua University Hospital, University of Padua, 35122 Padova, Italy;
| | - Giuliano Di Pierro
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Barbara Toffoli
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Andrea Grillo
- UCO Medicina Clinica, ASUGI, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (M.G.); (A.G.); (F.F.) (B.F.); (P.T.)
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Marco Bressan
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Marco Fiorentin
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Lorenzo Di Luozzo
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Fabio Fischetti
- UCO Medicina Clinica, ASUGI, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (M.G.); (A.G.); (F.F.) (B.F.); (P.T.)
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Margherita Zen
- Department of Medicine, Padua University Hospital, University of Padua, 35122 Padova, Italy;
| | - Bruno Fabris
- UCO Medicina Clinica, ASUGI, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (M.G.); (A.G.); (F.F.) (B.F.); (P.T.)
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Stella Bernardi
- UCO Medicina Clinica, ASUGI, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (M.G.); (A.G.); (F.F.) (B.F.); (P.T.)
- Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (G.D.P.); (B.T.); (M.B.); (M.F.); (L.D.L.)
| | - Paola Tomietto
- UCO Medicina Clinica, ASUGI, Cattinara Teaching Hospital, Strada di Fiume 447, 34149 Trieste, Italy; (M.G.); (A.G.); (F.F.) (B.F.); (P.T.)
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Li D, Wu S, Tang L, Chen S, Cui F, Ma Y, Liu R, Wang J, Tian Y. Long-term exposure to reduced specific-size ambient particulate matter and progression of arterial stiffness among Chinese adults. JOURNAL OF HAZARDOUS MATERIALS 2024; 466:133482. [PMID: 38246055 DOI: 10.1016/j.jhazmat.2024.133482] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 12/22/2023] [Accepted: 01/08/2024] [Indexed: 01/23/2024]
Abstract
To assess the associations of ambient specific-size PM with brachial-ankle pulse wave velocity (baPWV) and the progression of arterial stiffness. Participants were included from the Kailuan study, the cross-sectional study involved 36,486 participants, while the longitudinal study enrolled 16,871 participants. PM exposures was assessed through satellite-based random forest approaches at a 1 km resolution. Initial observations indicated a link between baseline baPWV and heightened levels of PM1, PM2.5, and PM10 exposure, and greater effects were observed for PM1 (β: 22.52, 95% CI: 18.14-26.89), followed by PM2.5 (β: 9.76, 95% CI: 7.52-12.00), and PM10 (β: 8.88, 95% CI: 7.32-10.45). Furthermore, the growth rate of baPWV was higher in participants exposed to high levels of PM1 exposure (β: 2.77, 95% CI: 1.19-4.35), succeeded by PM2.5 and PM10. Throughout a median follow-up period of 4.04 years, arterial stiffness was diagnosed in 1709 subjects. Long-term exposure to PM was linked with an increased risk of incident arterial stiffness, estimated HR for fixed 10 µg/m3 increments in annual average PM1 was 2.20 (95% CI: 2.01-2.42), PM2.5 was 1.48 (95% CI: 1.41-1.55), and PM10 1.32 (95% CI: 1.27-1.36). PM had a greater impact on men and older individuals (P for interaction <0.001). Long-term exposures to ambient PM1, PM2.5, and PM10 were positively associated with baPWV and an increased risk of arterial stiffness. Higher estimated effects were observed for PM1 than PM2.5 and PM10.
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Affiliation(s)
- Dankang Li
- Ministry of Education Key Laboratory of Environment and Health, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, Wuhan 430030, China
| | - Shouling Wu
- Department of Cardiology, Kailuan Hospital, North China University of Science and Technology, No.57 Xinhua East Road, Tangshan City 063001, China
| | - Linxi Tang
- Ministry of Education Key Laboratory of Environment and Health, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, Wuhan 430030, China
| | - Shuohua Chen
- Department of Cardiology, Kailuan Hospital, North China University of Science and Technology, No.57 Xinhua East Road, Tangshan City 063001, China
| | - Feipeng Cui
- Ministry of Education Key Laboratory of Environment and Health, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, Wuhan 430030, China
| | - Yudiyang Ma
- Ministry of Education Key Laboratory of Environment and Health, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, Wuhan 430030, China
| | - Run Liu
- Ministry of Education Key Laboratory of Environment and Health, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, Wuhan 430030, China
| | - Jianing Wang
- Ministry of Education Key Laboratory of Environment and Health, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, Wuhan 430030, China
| | - Yaohua Tian
- Ministry of Education Key Laboratory of Environment and Health, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No.13 Hangkong Road, Wuhan 430030, China.
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10
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Meng H, Cheng IT, Yan BPY, Lee AP, So H, Tam LS. Moderate and high disease activity levels increase the risk of subclinical atherosclerosis progression in early rheumatoid arthritis: a 5-year prospective study. RMD Open 2024; 10:e003488. [PMID: 38199848 PMCID: PMC10806479 DOI: 10.1136/rmdopen-2023-003488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 12/14/2023] [Indexed: 01/12/2024] Open
Abstract
OBJECTIVES To elucidate the association between different disease activity levels over time on long-term vascular outcomes in patients with early rheumatoid arthritis (ERA). METHODS This was a 5-year prospective study. Patients with consecutive ERA without overt cardiovascular disease (CVD) were recruited to receive 1 year of tight-control treatment followed by standard-of-care management. High-resolution carotid ultrasound was assessed at baseline and year 5. The primary outcome was subclinical atherosclerosis progression (AP+), defined as the occurrence of incident plaque, increased region harbouring plaques and/or maximum carotid intima-media thickness progression ≥0.9 mm at year 5. Inflammatory burden during the follow-up period was represented by the cumulative average Disease Activity Score 28-erythrocyte sedimentation rate (ca-DAS28-ESR). Persistent low disease activity (LDA) or remission state was defined as ca-DAS28-ESR≤3.2. RESULTS One-hundred and four patients with ERA (age: 52±11 years, 81 (77.9%) female) were included in this analysis. Fifty-two (50%) patients achieved persistent LDA or remission and 42 patients (40.4%) had AP+. Patients in the AP+ group were older and had more traditional cardiovascular risk factors at baseline. Multivariate logistic regression analysis revealed that patients with persistent moderate or high disease activity (ca-DAS28-ESR>3.2) had a significantly increased risk of AP+ (OR 5.05, 95% CI 1.53, 16.64, p=0.008) compared with those who achieved persistent remission. The risk of AP+ was similar in patients who achieved persistent LDA and remission. CONCLUSIONS Achieving persistent LDA or remission may prevent progression of atherosclerosis in ERA. A treat-to-target approach aiming at sustained LDA or remission may reduce the risk of CVD by preventing AP+.
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Affiliation(s)
- Huan Meng
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Isaac T Cheng
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Bryan Ping Yen Yan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Alex P Lee
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Ho So
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Lai-Shan Tam
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong
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11
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Campillo JT, Dupasquier V, Lebredonchel E, Rancé LG, Hemilembolo MC, Pion SDS, Boussinesq M, Missamou F, Perez Martin A, Chesnais CB. Association between arterial stiffness and Loa loa microfilaremia in a rural area of the Republic of Congo: A population-based cross-sectional study (the MorLo project). PLoS Negl Trop Dis 2024; 18:e0011915. [PMID: 38241411 PMCID: PMC10830006 DOI: 10.1371/journal.pntd.0011915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 01/31/2024] [Accepted: 01/12/2024] [Indexed: 01/21/2024] Open
Abstract
BACKGROUND Loa loa filariasis (loiasis) is still considered a relatively benign disease. However, recent epidemiologic data suggest increased mortality and morbidity in L. loa infected individuals. We aimed to examine whether the density of L. loa microfilariae (mfs) in the blood is associated with cardiovascular disease. METHODOLOGY Using a point-of-care device (pOpmètre), we conducted a cross-sectional study to assess arterial stiffness and peripheral arterial disease (PAD) in 991 individuals living in a loiasis-endemic rural area in the Republic of the Congo. Microfilaremic individuals were matched for age, sex and village of residence with 2 amicrofilaremic subjects. We analyzed markers of arterial stiffness (Pulse-Wave Velocity, PWV), PAD (Ankle-Brachial Index, ABI) and cardiovascular health (Pulse Pressure, PP). The analysis considered parasitological results (L. loa microfilarial density [MFD], soil-transmitted helminths infection, asymptomatic malaria and onchocerciasis), sociodemographic characteristics and known cardiovascular risk factors (body mass index, smoking status, creatininemia, blood pressure). PRINCIPAL FINDINGS Among the individuals included in the analysis, 192/982 (19.5%) and 137/976 (14.0%) had a PWV or an ABI considered out of range, respectively. Out of range PWV was associated with younger age, high mean arterial pressure and high L. loa MFD. Compared to amicrofilaremic subjects, those with more than 10,000 mfs/mL were 2.17 times more likely to have an out of range PWV (p = 0.00). Factors significantly associated with PAD were older age, low pulse rate, low body mass index, smoking, and L. loa microfilaremia. Factors significantly associated with an elevation of PP were older age, female sex, high average blood pressure, low pulse rate and L. loa microfilaremia. CONCLUSION A potential link between high L. loa microfilaremia and cardiovascular health deterioration is suggested. Further studies are required to confirm and explore this association.
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Affiliation(s)
- Jérémy T. Campillo
- TransVIHMI, Université de Montpellier, INSERM Unité 1175, Institut de Recherche pour le Développement (IRD), Montpellier, France
| | - Valentin Dupasquier
- Department of Cardiology, Montpellier University Hospital, Montpellier, France
| | - Elodie Lebredonchel
- Département de Biochimie, Hôpitaux Universitaires Paris Nord Val de Seine–site Bichat, Assistance Publique des Hôpitaux de Paris, Paris, France
| | - Ludovic G. Rancé
- Department of Anesthesiology and Critical Care Medicine, Montpellier University Hospital, Montpellier, France
| | - Marlhand C. Hemilembolo
- TransVIHMI, Université de Montpellier, INSERM Unité 1175, Institut de Recherche pour le Développement (IRD), Montpellier, France
- Programme National de Lutte contre l’Onchocercose, Direction de l’Épidémiologie et de la Lutte contre la Maladie, Ministère de la Santé et de la Population, Brazzaville, Republic of Congo
| | - Sébastien D. S. Pion
- TransVIHMI, Université de Montpellier, INSERM Unité 1175, Institut de Recherche pour le Développement (IRD), Montpellier, France
| | - Michel Boussinesq
- TransVIHMI, Université de Montpellier, INSERM Unité 1175, Institut de Recherche pour le Développement (IRD), Montpellier, France
| | - François Missamou
- Programme National de Lutte contre l’Onchocercose, Direction de l’Épidémiologie et de la Lutte contre la Maladie, Ministère de la Santé et de la Population, Brazzaville, Republic of Congo
| | - Antonia Perez Martin
- Vascular Medicine Laboratory, Nîmes University Hospital, Nîmes, France
- IDESP, Université de Montpellier, INSERM, Montpellier, France
| | - Cédric B. Chesnais
- TransVIHMI, Université de Montpellier, INSERM Unité 1175, Institut de Recherche pour le Développement (IRD), Montpellier, France
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Cheng DCY, Climie RE, Shu M, Grieve SM, Kozor R, Figtree GA. Vascular aging and cardiovascular disease: pathophysiology and measurement in the coronary arteries. Front Cardiovasc Med 2023; 10:1206156. [PMID: 38089775 PMCID: PMC10715672 DOI: 10.3389/fcvm.2023.1206156] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Accepted: 11/13/2023] [Indexed: 11/29/2024] Open
Abstract
Age is a key risk factor for cardiovascular disease, including atherosclerosis. However, pathophysiological disease processes in the arteries are not an inevitable feature of aging. Large cohort studies with arterial phenotyping along with clinical and demographic data are essential to better understand factors related to the susceptibility or resilience to age-related vascular pathophysiology in humans. This review explores the mechanisms by which vascular structure and function alters with age, and how these changes relate to cardiovascular pathophysiology and disease. Features of vascular aging in the coronary arteries have historically been difficult to quantify pre-mortem due to their size and location. However, non-invasive imaging modalities including CT Coronary Angiogram are now being used to assess coronary vascular age, and further advances in imaging analysis such as the CT Fat Attenuation Index will help provide further measurement of features associated with coronary vascular aging. Currently, markers of vascular aging are not used as therapeutic targets in routine clinical practice, but non-pharmacological interventions including aerobic exercise and low salt diet, as well as anti-hypertensives have been demonstrated to reduce arterial stiffness. Advances in imaging technology, both in acquisition and advanced analysis, as well as harmonisation of measurements for researchers across the globe will be invaluable in understanding what constitutes healthy vascular aging and in identifying features of vascular aging that are associated with coronary artery disease and its adverse outcomes. Assessing such images in large cohorts can facilitate improved definitions of resilient and susceptible phenotypes to vascular aging in the coronary arteries. This is a critical step in identifying further risk factors and biomarkers within these groups and driving forward the development of novel therapies aimed at slowing or stopping age-related vascular changes in the coronary arteries.
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Affiliation(s)
- Daniel C. Y. Cheng
- Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, NSW, Australia
| | - Rachel E. Climie
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
| | - Matthew Shu
- Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Stuart M. Grieve
- Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, NSW, Australia
- Imaging and Phenotyping Laboratory, Charles Perkins Centre and Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Rebecca Kozor
- Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, NSW, Australia
- Department of Cardiology, Royal North Shore Hospital, Sydney, NSW, Australia
| | - Gemma A. Figtree
- Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, NSW, Australia
- Imaging and Phenotyping Laboratory, Charles Perkins Centre and Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
- Department of Cardiology, Royal North Shore Hospital, Sydney, NSW, Australia
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González LDM, Romero-Orjuela SP, Rabeya FJ, del Castillo V, Echeverri D. Age and vascular aging: an unexplored frontier. Front Cardiovasc Med 2023; 10:1278795. [PMID: 38028481 PMCID: PMC10665864 DOI: 10.3389/fcvm.2023.1278795] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 10/03/2023] [Indexed: 12/01/2023] Open
Abstract
Vascular age is an emerging field in cardiovascular risk assessment. This concept includes multifactorial changes in the arterial wall, with arterial stiffness as its most relevant manifestation, leading to increased arterial pressure and pulsatile flow in the organs. Today, the approved test for measuring vascular age is pulse wave velocity, which has been proven to predict cardiovascular events. Furthermore, vascular phenotypes, such as early vascular aging and "SUPERNOVA," representing phenotypic extremes of vascular aging, have been found. The identification of these phenotypes opens a new field of study in cardiovascular physiology. Lifestyle interventions and pharmacological therapy have positively affected vascular health, reducing arterial stiffness. This review aims to define the concepts related to vascular age, pathophysiology, measurement methods, clinical signs and symptoms, and treatment.
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Affiliation(s)
- Laura del Mar González
- Department of Cardiology, Fundación Cardioinfantil–Instituto de Cardiología, Bogotá, Colombia
| | | | - Fernando J. Rabeya
- School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia
| | - Valeria del Castillo
- Department of Cardiology, Fundación Cardioinfantil–Instituto de Cardiología, Bogotá, Colombia
| | - Darío Echeverri
- Department of Cardiology, Fundación Cardioinfantil–Instituto de Cardiología, Bogotá, Colombia
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Yang N, Yang K, Pan S, He Q, Jin J. Progress in the application of the neutrophil-to-lymphocyte ratio in dialysis-related complications. Ren Fail 2023; 45:2259996. [PMID: 37791567 PMCID: PMC10552595 DOI: 10.1080/0886022x.2023.2259996] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 09/12/2023] [Indexed: 10/05/2023] Open
Abstract
The neutrophil-to-lymphocyte ratio (NLR) is a novel predictive biomarker that reflects systemic inflammatory status and is routinely measured in blood tests. Owing to its ease of use and affordability, it is being increasing used as a prognostic indicator of cardiovascular disease, tumors, autoimmune disorders, and kidney disease. In recent years, a number of studies have demonstrated the clinical utility of the NLR in identifying and predicting complications associated with hemodialysis and peritoneal dialysis, including cardiovascular disease and infection. This review aimed to provide a new perspective on the application of the NLR as a valuable tool enabling clinicians to better assess the occurrence and prognosis of complications in patients undergoing dialysis.
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Affiliation(s)
- Nan Yang
- Department of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, China
| | - Kaibi Yang
- Department of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, China
| | - Shujun Pan
- Department of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, China
| | - Qiang He
- Department of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, China
| | - Juan Jin
- Department of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, China
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Gerganov G, Georgiev T, Dimova M, Shivacheva T. Vascular effects of biologic and targeted synthetic antirheumatic drugs approved for rheumatoid arthritis: a systematic review. Clin Rheumatol 2023; 42:2651-2676. [PMID: 36991244 DOI: 10.1007/s10067-023-06587-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/20/2023] [Accepted: 03/24/2023] [Indexed: 03/31/2023]
Abstract
BACKGROUND Rheumatoid arthritis (RA) increases the risk of cardiovascular disease (CVD), with inflammation playing a key role. Biologic and targeted synthetic drugs used to treat RA can induce systemic immunomodulation and may have pleiotropic effects on vascular function, making it crucial to investigate their impact on CVD risk in RA patients. METHODS A systematic review of the literature was conducted to investigate the impact of biologic and targeted synthetic treatments approved for RA on various cardiovascular markers, including endothelial function, arterial stiffness, and subclinical atherosclerosis. Our analysis included a search of the MedLine (via PubMed) and Web of Science databases using a pre-determined search strategy. We conducted a narrative synthesis of the included studies due to heterogeneity in study design and outcome measures. RESULTS From an initial pool of 647 records, we excluded 327 studies based on their titles and abstracts, and we selected 182 studies for final examination. Ultimately, 58 articles met our inclusion criteria and were included in our systematic review. Our analysis of these studies revealed a positive effect of biologic and targeted synthetic therapies on vascular dysfunction associated with RA. However, the impact of these treatments on subclinical atherosclerosis was inconsistent. CONCLUSION Overall, our systematic review provides important insights into the potential cardiovascular benefits of biologic and targeted synthetic treatments for RA by a still unknown mechanism. These findings can inform clinical practice and contribute to our understanding of their possible effects on early vascular pathology. Key Points • Great heterogeneity of methods are used to evaluate the endothelial function and arterial stiffness in patients with RA on biologic and targeted synthetic antirheumatic drugs. • Most studies have shown a considerable improvement in endothelial function and arterial stiffness with TNFi, despite some studies reporting only transient or no improvement. • Anakinra and tocilizumab may have a beneficial effect on vascular function and endothelial injury, as indicated by increased FMD, coronary flow reserve, and reduced levels of biomarkers of endothelial function, while the overall impact of JAKi and rituximab remains inconclusive based on the reviewed studies. • To fully comprehend the distinctions between biologic therapies, more long-term, well-designed clinical trials are necessary using a homogeneous methodology.
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Affiliation(s)
- Georgi Gerganov
- Department of Propedeutics of Internal Medicine, Faculty of Medicine, Medical University - Varna, 9002, Varna, Bulgaria
- Clinic of Rheumatology, University Hospital St. Marina - Varna, 9010, Varna, Bulgaria
| | - Tsvetoslav Georgiev
- Clinic of Rheumatology, University Hospital St. Marina - Varna, 9010, Varna, Bulgaria.
- First Department of Internal Medicine, Faculty of Medicine, Medical University - Varna, 9002, Varna, Bulgaria.
| | - Maria Dimova
- Department of Propedeutics of Internal Medicine, Faculty of Medicine, Medical University - Varna, 9002, Varna, Bulgaria
- Clinic of Internal Medicine, University Hospital St. Marina - Varna, 9010, Varna, Bulgaria
| | - Tanya Shivacheva
- Clinic of Rheumatology, University Hospital St. Marina - Varna, 9010, Varna, Bulgaria
- First Department of Internal Medicine, Faculty of Medicine, Medical University - Varna, 9002, Varna, Bulgaria
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16
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Kerch G. Nanocomposite Hydrogels and Extracellular Matrix-Advantages and Associated Risks. Gels 2023; 9:754. [PMID: 37754435 PMCID: PMC10530377 DOI: 10.3390/gels9090754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 09/08/2023] [Accepted: 09/09/2023] [Indexed: 09/28/2023] Open
Abstract
Hydrogels can be considered as mimics of the extracellular matrix (ECM). Through integrins, the cytoskeleton is connected to the ECM, and cytoskeleton tension depends on ECM stiffness. A number of age-related diseases depend on cellular processes related to cytoskeleton function. Some examples of cancer initiation and progression and heart disease in relation to ECM stiffness have been analyzed. The incorporation of rigid particles into the ECM can increase ECM stiffness and promote the formation of internal residual stresses. Water migration, changes in water binding energy to biomactomolecules, and changes in the state of water from tightly bound water to free and loosely bound water lead to changes in the stiffness of the ECM. Cardiac tissue engineering, ECM stiffness and cancer, the equivalence of ECM stiffness, oxidative stress, inflammation, multi-layer polyelectrolyte complex hydrogels and bioprinting, residual internal stresses, viscoelastic hydrogels, hydrogel nanocomposites, and the effect of water have been reported. Special attention has been paid to the role of bound water and internal stresses in ECM stiffness. The risks related to rigid particle incorporation into the ECM have been discussed. The potential effect of polyphenols, chitosan, and chitosan oligosaccharide on ECM stiffness and the potential for anti-TNF-α and anti-NF-κB therapies have been discussed.
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Affiliation(s)
- Garry Kerch
- Faculty of Materials Science and Applied Chemistry, Riga Technical University, P. Valdena 3, 1048 Riga, Latvia
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17
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Abdulmajid B, Blanken AB, van Geel EH, Daams JG, Nurmohamed MT. Effect of TNF inhibitors on arterial stiffness and intima media thickness in rheumatoid arthritis: a systematic review and meta-analysis. Clin Rheumatol 2023; 42:999-1011. [PMID: 36645550 PMCID: PMC10017587 DOI: 10.1007/s10067-023-06505-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 12/17/2022] [Accepted: 12/31/2022] [Indexed: 01/17/2023]
Abstract
Controlling inflammation with tumor necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA) patients is hypothesized to reduce their cardiovascular risk. We performed a systematic review and meta-analysis on the effects of TNF inhibitors on arterial stiffness and carotid intima media thickness (IMT) in RA. MEDLINE, EMBASE, clinicaltrials.gov , and WHO Clinical Trials Registry were searched up to September 2021 for randomized controlled trials, prospective cohort studies, and nonrandomized clinical trials evaluating the effects of TNF inhibitors on pulse wave velocity (PWV), augmentation index (AIx), and IMT in RA. A meta-analysis was performed to assess changes of these measures after therapy during different follow-up periods. Risk of bias assessment was performed using an adjusted Downs and Black checklist (INPLASY: 2022-1-0131). Thirty studies were identified from 1436 records, of which 23 were included in the meta-analysis. PWV and AIx showed a decrease after treatment (PWV: mean difference (MD) -0.51 m/s (95% CI: -0.96, -0.06), p=0.027; AIx: MD -0.57% (95% CI: -2.11, 0.96), p=0.463, sensitivity analysis AIx: MD -1.21% (95% CI: -2.60, 0.19), p=0.089). For IMT, there was a slight increase in the first months of follow-up, but this disappeared on the long-term (overall timepoints MD -0.01 mm (95% CI: -0.04, 0.02), p=0.615). Heterogeneity was high in the overall analyses and subgroups with long follow-up periods (≥12 months). The included studies showed mixed results of the effects of TNF inhibitors on the surrogate markers. The pooled results suggest that PWV and AIx decrease over time, while IMT remains stable. This indicates a favorable effect of TNF inhibitors on the cardiovascular disease risk, all the more since these markers also increase with age.
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Affiliation(s)
- Bafrin Abdulmajid
- Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Location Reade, Amsterdam Dr. Jan van Breemenstraat 2, PO Box 58271, 1040 HG, Amsterdam, The Netherlands. .,Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.
| | - Annelies B Blanken
- Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Location Reade, Amsterdam Dr. Jan van Breemenstraat 2, PO Box 58271, 1040 HG, Amsterdam, The Netherlands.,Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Location Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands.,Department of Medical Library, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands
| | - Eva H van Geel
- Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Location Reade, Amsterdam Dr. Jan van Breemenstraat 2, PO Box 58271, 1040 HG, Amsterdam, The Netherlands.,Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Location Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands
| | - Joost G Daams
- Department of Medical Library, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands
| | - Michael T Nurmohamed
- Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Location Reade, Amsterdam Dr. Jan van Breemenstraat 2, PO Box 58271, 1040 HG, Amsterdam, The Netherlands.,Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Location Amsterdam UMC, VU University Medical Center, Amsterdam, The Netherlands.,Department of Medical Library, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands
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18
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Ranatunga S, Kulkarni B, Kinra S, Ebeling PR, Zengin A. Sex-specific associations between markers of arterial stiffness and bone mineral density in Indian men and women. Bone 2023; 169:116686. [PMID: 36720333 DOI: 10.1016/j.bone.2023.116686] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 01/18/2023] [Accepted: 01/26/2023] [Indexed: 01/30/2023]
Abstract
BACKGROUND Osteoporosis and cardiovascular disease (CVD) share common risk factors, yet both are usually underdiagnosed in the absence of major complications. We investigated associations between arterial stiffness, cardiac workload, carotid intima media thickness (CIMT) and areal bone mineral density (aBMD) in Indian adults. METHODS Men and women aged >45 years from the Andhra Pradesh Children and Parents Study (APCAPS) were included for cross-sectional analysis (521 women and 696 men). Dual energy x-ray absorptiometry (DXA) measured aBMD at the whole body, total hip and lumbar spine. Supine blood pressure and heart rate were measured and used to calculate rate pressure product and pulse pressure; augmentation index, pulse wave velocity and CIMT were measured. Sex-interactions were tested (denoted as p-int); adjustments were made for confounders. Data were expressed as SD differences with 95 % confidence intervals. RESULTS There were significant negative associations between pulse pressure and aBMD at all sites in women only. In unadjusted analyses, for every 1SD increase in pulse pressure, women had greater negative differences in aBMD at the whole body (-0.13 vs 0.007), total hip (-0.20 vs -0.05) and lumbar spine (-0.12 vs 0.05) compared with men. After adjustments, sex differences remained. Similar negative associations were seen between pulse wave velocity and augmentation index with aBMD in women only. There were no sex differences between CIMT and rate pressure product with aBMD. CONCLUSIONS Markers of arterial stiffness are associated with poorer bone health in Indian women, but not in men. There is a need to identify the shared risk factors and markers of arterial stiffness and poor bone health to detect those who require co-management of these diseases to prevent cardiovascular events and fractures.
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Affiliation(s)
- Shasheni Ranatunga
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, VIC, Australia
| | - Bharati Kulkarni
- Clinical Division, ICMR-National Institute of Nutrition, Jamai Osmania PO, Hyderabad, India
| | - Sanjay Kinra
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
| | - Peter R Ebeling
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, VIC, Australia
| | - Ayse Zengin
- Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, VIC, Australia.
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19
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Kerch G. Severe COVID-19-A Review of Suggested Mechanisms Based on the Role of Extracellular Matrix Stiffness. Int J Mol Sci 2023; 24:1187. [PMID: 36674700 PMCID: PMC9861790 DOI: 10.3390/ijms24021187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 01/02/2023] [Accepted: 01/04/2023] [Indexed: 01/11/2023] Open
Abstract
The severity of COVID-19 commonly depends on age-related tissue stiffness. The aim was to review publications that explain the effect of microenvironmental extracellular matrix stiffness on cellular processes. Platelets and endothelial cells are mechanosensitive. Increased tissue stiffness can trigger cytokine storm with the upregulated expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha and interleukin IL-6, and tissue integrity disruption, leading to enhanced virus entry and disease severity. Increased tissue stiffness in critically ill COVID-19 patients triggers platelet activation and initiates plague formation and thrombosis development. Cholesterol content in cell membrane increases with aging and further enhances tissue stiffness. Membrane cholesterol depletion decreases virus entry to host cells. Membrane cholesterol lowering drugs, such as statins or novel chitosan derivatives, have to be further developed for application in COVID-19 treatment. Statins are also known to decrease arterial stiffness mitigating cardiovascular diseases. Sulfated chitosan derivatives can be further developed for potential use in future as anticoagulants in prevention of severe COVID-19. Anti-TNF-α therapies as well as destiffening therapies have been suggested to combat severe COVID-19. The inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells pathway must be considered as a therapeutic target in the treatment of severe COVID-19 patients. The activation of mechanosensitive platelets by higher matrix stiffness increases their adhesion and the risk of thrombus formation, thus enhancing the severity of COVID-19.
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Affiliation(s)
- Garry Kerch
- Faculty of Materials Science and Applied Chemistry, Riga Technical University, 1048 Riga, Latvia
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20
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Soós B, Hamar A, Pusztai A, Czókolyová M, Végh E, Szamosi S, Pethő Z, Gulyás K, Kerekes G, Szántó S, Szűcs G, Christians U, Klawitter J, Seres T, Szekanecz Z. Effects of tofacitinib therapy on arginine and methionine metabolites in association with vascular pathophysiology in rheumatoid arthritis: A metabolomic approach. Front Med (Lausanne) 2022; 9:1011734. [PMID: 36438060 PMCID: PMC9684209 DOI: 10.3389/fmed.2022.1011734] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 10/26/2022] [Indexed: 11/11/2022] Open
Abstract
Introduction Rheumatoid arthritis (RA) has been associated with changes in lipid, arginine and NO metabolism with increased cardiovascular (CV) risk. The aim of this study is to evaluate the effect of tofacitinib, a Janus kinase (JAK) inhibitor, on arginine and methionine metabolism in correlation with inflammation, functional and pathological vascular changes during one-year treatment of patients with RA. Materials and methods Thirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib for 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) levels. We assessed brachial artery flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) by ultrasound at baseline and after 6 and 12 months. We also determined plasma L-arginine, L-citrulline, L-ornithine, inducible nitric oxide synthase (iNOS), asymmetric (ADMA) and symmetric dimethylarginine (SDMA), L-N-monomethyl-arginine (L-NMMA), cysteine, homocysteine, and methionine levels at these time points. Results Twenty-six patients (13 on each arm) completed the study. CRP, ESR and DAS28 decreased significantly during one-year treatment with tofacitinib. Arginine and ADMA showed a negative univariate correlation with CRP but not with FMD, PWV or IMT. Tofacitinib at 10 mg bid significantly increased L-arginine, L-ornithine, iNOS and methionine levels after 12 months. ADMA and SDMA levels did not change in our study. Methionine showed negative correlation with FMD at baseline and positive correlation with PWV after 12 months. No change was observed in FMD and PWV but a significant increase was measured in IMT at 6 and 12 months. Multivariate analysis indicated variable correlations of L-arginine, L-citrulline, ADMA, L-NMMA, homocysteine and methionine with DAS28, CRP, ESR and RF but not with anti-CCP after one-year treatment. With respect to vascular pathophysiology, only PWV and methionine correlated with each other. Conclusion One-year tofacitinib treatment suppressed systemic inflammation and improved functional status in RA. FMD, PWV have not been affected by one-year tofacitinib treatment., while IMT increased further despite treatment. Increased arginine and methionine might contribute to the anti-inflammatory effects of tofacitinib. Increased arginine availability with no changing ADMA may protect FMD and PWV from deterioration. The increase of IMT in the anti-inflammatory environment cannot be explained by arginine or methionine metabolism in this study.
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Affiliation(s)
- Boglárka Soós
- Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Attila Hamar
- Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Anita Pusztai
- Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Monika Czókolyová
- Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Edit Végh
- Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Szilvia Szamosi
- Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Zsófia Pethő
- Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Katalin Gulyás
- Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - György Kerekes
- Intensive Care Unit, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Sándor Szántó
- Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- Department of Sports Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Gabriella Szűcs
- Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Uwe Christians
- Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Jelena Klawitter
- Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Tamás Seres
- Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Zoltán Szekanecz
- Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- *Correspondence: Zoltán Szekanecz,
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21
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Maqsood MH, Weber BN, Haberman RH, Lo Sicco KI, Bangalore S, Garshick MS. Cardiovascular and Venous Thromboembolic Risk With Janus Kinase Inhibitors in
Immune‐Mediated
Inflammatory Diseases: A Systematic Review and
Meta‐Analysis
of Randomized Trials. ACR Open Rheumatol 2022; 4:912-922. [PMID: 35903881 PMCID: PMC9555201 DOI: 10.1002/acr2.11479] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 05/25/2022] [Accepted: 05/31/2022] [Indexed: 11/10/2022] Open
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22
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The Gut Microbiota and Vascular Aging: A State-of-the-Art and Systematic Review of the Literature. J Clin Med 2022; 11:jcm11123557. [PMID: 35743626 PMCID: PMC9224769 DOI: 10.3390/jcm11123557] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 06/17/2022] [Accepted: 06/18/2022] [Indexed: 12/15/2022] Open
Abstract
The gut microbiota is a critical regulator of human physiology, deleterious changes to its composition and function (dysbiosis) have been linked to the development and progression of cardiovascular diseases. Vascular ageing (VA) is a process of progressive stiffening of the arterial tree associated with arterial wall remodeling, which can precede hypertension and organ damage, and is associated with cardiovascular risk. Arterial stiffness has become the preferred marker of VA. In our systematic review, we found an association between gut microbiota composition and arterial stiffness, with two patterns, in most animal and human studies: a direct correlation between arterial stiffness and abundances of bacteria associated with altered gut permeability and inflammation; an inverse relationship between arterial stiffness, microbiota diversity, and abundances of bacteria associated with most fit microbiota composition. Interventional studies were able to show a stable link between microbiota modification and arterial stiffness only in animals. None of the human interventional trials was able to demonstrate this relationship, and very few adjusted the analyses for determinants of arterial stiffness. We observed a lack of large randomized interventional trials in humans that test the role of gut microbiota modifications on arterial stiffness, and take into account BP and hemodynamic alterations.
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23
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Pierce GL, Coutinho TA, DuBose LE, Donato AJ. Is It Good to Have a Stiff Aorta with Aging? Causes and Consequences. Physiology (Bethesda) 2022; 37:154-173. [PMID: 34779281 PMCID: PMC8977146 DOI: 10.1152/physiol.00035.2021] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 10/28/2021] [Accepted: 11/08/2021] [Indexed: 01/09/2023] Open
Abstract
Aortic stiffness increases with advancing age, more than doubling during the human life span, and is a robust predictor of cardiovascular disease (CVD) clinical events independent of traditional risk factors. The aorta increases in diameter and length to accommodate growing body size and cardiac output in youth, but in middle and older age the aorta continues to remodel to a larger diameter, thinning the pool of permanent elastin fibers, increasing intramural wall stress and resulting in the transfer of load bearing onto stiffer collagen fibers. Whereas aortic stiffening in early middle age may be a compensatory mechanism to normalize intramural wall stress and therefore theoretically "good" early in the life span, the negative clinical consequences of accelerated aortic stiffening beyond middle age far outweigh any earlier physiological benefit. Indeed, aortic stiffness and the loss of the "windkessel effect" with advancing age result in elevated pulsatile pressure and flow in downstream microvasculature that is associated with subclinical damage to high-flow, low-resistance organs such as brain, kidney, retina, and heart. The mechanisms of aortic stiffness include alterations in extracellular matrix proteins (collagen deposition, elastin fragmentation), increased arterial tone (oxidative stress and inflammation-related reduced vasodilators and augmented vasoconstrictors; enhanced sympathetic activity), arterial calcification, vascular smooth muscle cell stiffness, and extracellular matrix glycosaminoglycans. Given the rapidly aging population of the United States, aortic stiffening will likely contribute to substantial CVD burden over the next 2-3 decades unless new therapeutic targets and interventions are identified to prevent the potential avalanche of clinical sequelae related to age-related aortic stiffness.
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Affiliation(s)
- Gary L Pierce
- Department of Health and Human Physiology, University of Iowa, Iowa City, Iowa
- Department of Internal Medicine, University of Iowa, Iowa City, Iowa
- Abboud Cardiovascular Research Center, University of Iowa, Iowa City, Iowa
- Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa
| | - Thais A Coutinho
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Divisions of Cardiology and Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | - Lyndsey E DuBose
- Division of Geriatrics, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Anthony J Donato
- Department of Internal Medicine, University of Utah, Salt Lake City, Utah
- Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah
- Department of Biochemistry, University of Utah, Salt Lake City, Utah
- Geriatric Research Education and Clinical Center, VA Salt Lake City, Salt Lake City, Utah
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24
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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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25
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Choe JY, Park SH, Kim SK. Augmentation index, but not pulse wave velocity, is associated with disease activity in rheumatoid arthritis. EUR J INFLAMM 2022. [DOI: 10.1177/1721727x221090158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Rheumatoid arthritis (RA) is associated with premature atherosclerosis and increased risk of cardiovascular disease (CVD). The purpose of this study was to assess the relationship between disease activity and arterial stiffness indexes for CVD in RA patients. Two hundred twenty-two female RA patients were retrospectively recruited. Non-invasive arterial stiffness was assessed by brachial-ankle PWV (baPWV) and ankle-brachial index (ABI) using pulse wave analyses and the augmentation index (AIx). The AIx was classified into two groups of normal (grade 0) and abnormal (grade 1, 2, and 3). The baPWV was associated with only age and rheumatoid factor titer, but not disease activity index, DAS28-ESR. Univariate analysis indicated that AIx was related to body mass index, disease duration, and DAS28-ESR. In addition, the baPWV was associated with DAS28-ESR and disease duration after adjusting for confounding factors (β = 0.147, p = 0.032 and β = 0.183, p = 0.034, respectively). Multivariate logistic regression analysis showed that the tendency for abnormal AIx increased as DAS28-ESR increased, and the result was significant ( p for trend = 0.026). The results of this study indicated that the relationship between AIx and DAS28-ESR suggests that disease activity could affect arterial stiffness in RA.
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Affiliation(s)
- Jung-Yoon Choe
- Division of Rheumatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea
| | - Seo-Hyeon Park
- Division of Rheumatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea
| | - Seong-Kyu Kim
- Division of Rheumatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Republic of Korea
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Effects of Exercise Training on the Autonomic Nervous System with a Focus on Anti-Inflammatory and Antioxidants Effects. Antioxidants (Basel) 2022; 11:antiox11020350. [PMID: 35204231 PMCID: PMC8868289 DOI: 10.3390/antiox11020350] [Citation(s) in RCA: 82] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/04/2022] [Accepted: 02/07/2022] [Indexed: 02/01/2023] Open
Abstract
Studies show that the autonomic nervous system (ANS) has an important impact on health in general. In response to environmental demands, homeostatic processes are often compromised, therefore determining an increase in the sympathetic nervous system (SNS)’s functions and a decrease in the parasympathetic nervous system (PNS)’s functions. In modern societies, chronic stress associated with an unhealthy lifestyle contributes to ANS dysfunction. In this review, we provide a brief introduction to the ANS network, its connections to the HPA axis and its stress responses and give an overview of the critical implications of ANS in health and disease—focused specifically on the immune system, cardiovascular, oxidative stress and metabolic dysregulation. The hypothalamic–pituitary–adrenal axis (HPA), the SNS and more recently the PNS have been identified as regulating the immune system. The HPA axis and PNS have anti-inflammatory effects and the SNS has been shown to have both pro- and anti-inflammatory effects. The positive impact of physical exercise (PE) is well known and has been studied by many researchers, but its negative impact has been less studied. Depending on the type, duration and individual characteristics of the person doing the exercise (age, gender, disease status, etc.), PE can be considered a physiological stressor. The negative impact of PE seems to be connected with the oxidative stress induced by effort.
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Anthoulakis C, Mamopoulos A, Rousso D, Karagiannis A, Athanasiadis A, Grimbizis G, Athyros V. Arterial Stiffness as a Cardiovascular Risk Factor for the Development of Preeclampsia and Pharmacopreventive Options. Curr Vasc Pharmacol 2021; 20:52-61. [PMID: 34615450 DOI: 10.2174/1570161119666211006114258] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 08/08/2021] [Accepted: 08/18/2021] [Indexed: 11/22/2022]
Abstract
Arterial stiffness (AS) describes the rigidity of the arterial walls. Epidemiological studies have shown that increased AS is an independent predictive marker of cardiovascular (CV) morbidity and mortality in both pregnant and non-pregnant women. Preeclampsia (PE), a form of pregnancy-induced hypertension, affects approximately 5% of pregnancies worldwide. Preeclamptic women have a higher risk of CV disease (CVD), mainly because PE damages the heart's ability to relax between contractions. Different pharmacological approaches for the prevention of PE have been tested in clinical trials (e.g. aspirin, enoxaparin, metformin, pravastatin, and sildenafil citrate). In current clinical practice, only low-dose aspirin is used for PE pharmacoprevention. However, low-dose aspirin does not prevent term PE, which is the most common form of PE. Compromised vascular integrity precedes the onset of PE and therefore, AS assessment may constitute a promising predictive marker of PE. Several non-invasive techniques have been developed to assess AS. Compared with normotensive pregnancies, both carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx) are increased in PE. In view of simplicity, reliability, and reproducibility, there is an interest in oscillometric AS measurements in pregnancies complicated by PE.
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Affiliation(s)
- Christos Anthoulakis
- First Department of Obstetrics & Gynecology, "Papageorgiou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki. Greece
| | - Apostolos Mamopoulos
- Third Department of Obstetrics & Gynecology, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki. Greece
| | - David Rousso
- Third Department of Obstetrics & Gynecology, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki. Greece
| | - Asterios Karagiannis
- Second Propaedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki. Greece
| | - Apostolos Athanasiadis
- Third Department of Obstetrics & Gynecology, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki. Greece
| | - Grigoris Grimbizis
- First Department of Obstetrics & Gynecology, "Papageorgiou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki. Greece
| | - Vasilios Athyros
- Second Propaedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki. Greece
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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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Sleutjes JAM, van Lennep JER, van der Woude CJ, de Vries AC. Thromboembolic and atherosclerotic cardiovascular events in inflammatory bowel disease: epidemiology, pathogenesis and clinical management. Therap Adv Gastroenterol 2021; 14:17562848211032126. [PMID: 34377149 PMCID: PMC8323448 DOI: 10.1177/17562848211032126] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 05/27/2021] [Indexed: 02/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is associated with an increased risk of cardiovascular disease (CVD). The increased risk of CVD concerns an increased risk of venous thromboembolism (VTE), atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF), at corresponding relative risks of 2.5, 1.2 and 2.0, respectively, as compared with the general population. Especially young patients under the age of 40 years run a relatively high risk of these complications when compared with the general population. Chronic systemic inflammation causes a hypercoagulable state leading to the prothrombotic tendency characteristic of VTE, and accelerates all stages involved during atherogenesis in ASCVD. Increased awareness of VTE risk is warranted in patients with extensive colonic disease in both ulcerative colitis and Crohn's disease, as well as during hospitalization, especially when patients are scheduled for surgery. Similarly, critical periods for ASCVD events are the 3 months prior to and 3 months after an IBD-related hospital admission. The increased ASCVD risk is not fully explained by an increased prevalence of traditional risk factors and includes pro-atherogenc lipid profiles with high levels of small dense low-density lipoprotein cholesterol particles and dysfunctional high-density lipoprotein cholesterol. Risk factors associated with HF are location and extent of inflammation, female sex, and age exceeding 40 years. A dose-dependent increase of overall CVD risk has been reported for corticosteroids. Immunomodulating maintenance therapy might reduce CVD risk in IBD, not only by a direct reduction of chronic systemic inflammation but possibly also by a direct effect of IBD medication on platelet aggregation, endothelial function and lipid and glucose metabolism. More data are needed to define these effects accurately. Despite accumulating evidence on the increased CVD risk in IBD, congruent recommendations to develop preventive strategies are lacking. This literature review provides an overview of current knowledge and identifies gaps in evidence regarding CVD risk in IBD, by discussing epidemiology, pathogenesis, and clinical management.
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Affiliation(s)
- Jasmijn A. M. Sleutjes
- Department of Gastroenterology and Hepatology,
Erasmus Medical Center, Rotterdam, the Netherlands
| | | | - C. Janneke van der Woude
- Department of Gastroenterology and Hepatology,
Erasmus Medical Center, Rotterdam, the Netherlands
| | - Annemarie C. de Vries
- Department of Gastroenterology and Hepatology,
Erasmus Medical Center, Dr. Molewaterplein 40, Room Na-618, Rotterdam
3015GD, The Netherlands
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Arterial stiffness, the hidden face of cardiovascular risk in autoimmune and chronic inflammatory rheumatic diseases. Autoimmun Rev 2021; 20:102891. [PMID: 34229047 DOI: 10.1016/j.autrev.2021.102891] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 04/22/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND OBJECTIVE Cardiovascular diseases (CVD) are the leading causes of death in chronic inflammatory rheumatic diseases and are not solely explained by the increased prevalence of cardiovascular (CV) risk factors in this population. Arterial stiffness, assessed primarily by pulse wave velocity (PWV) and more indirectly by augmentation index (AIx), is a surrogate marker of CVD that should be considered. The objective of this review was to investigate the relationship between arterial stiffness and chronic inflammatory and/or autoimmune diseases. METHODS We performed a systemic literature review of articles published in Medline from January 2012 to April 2020 restricted to English languages and to human adults. We selected relevant articles about the relationship between arterial stiffness and rheumatoid arthritis, systemic lupus erythematosus, psoriasis, Sjogren's syndrome and ankylosing spondylitis. For each selected article, data on PWV and AIx were extracted and factors that may have an impact on arterial stiffness were identified. RESULTS A total of 214 references were identified through database searching and 82 of them were retained for analysis. Arterial stiffness is increased in chronic inflammatory and autoimmune diseases. Traditional CV risk factors such as hypertension and dyslipidemia accentuate this relationship. Current data are insufficient to determine whether disease activity significantly influences arterial stiffness, whereas disease duration seems rather critical. TNF-alpha inhibitors and cardiorespiratory fitness tend to decrease arterial stiffness. Finally, increased arterial stiffness leads to diastolic dysfunction, which is the main mechanism of heart failure in chronic inflammatory rheumatic diseases. CONCLUSION CV risk assessment in chronic inflammatory and autoimmune diseases should also rely on PWV and AIx.
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Xu T, Zhou F, Xu C, Chen A, Huang S, Zhou H. The relationship between brachial-ankle pulse wave velocity and peripheral blood lymphocyte subsets in hypertensives: a cross-sectional study. J Hum Hypertens 2021; 36:651-658. [PMID: 34117347 DOI: 10.1038/s41371-021-00553-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 05/01/2021] [Accepted: 05/14/2021] [Indexed: 11/09/2022]
Abstract
Arteriosclerosis is the common pathological basis of hypertension-related target organ damage, and pulse wave velocity (PWV) is commonly used to assess the degree of arterial stiffness. Previous studies have reported the correlation between peripheral blood inflammatory indicators and PWV in hypertensives, but few studies examined the role of immune cells in arteriosclerosis in the context of human hypertension. In order to enrich the understanding of this topic, we conducted a cross-sectional study on hospitalized hypertensives in Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2015 to February 2017 to investigate the relationship between brachial-ankle pulse wave velocity (baPWV) and peripheral blood lymphocyte subsets. Sixty-four eligible patients were enrolled in our study. The patients' blood pressure, height, body weight, and baPWV were collected, along with the lab results of their peripheral complete blood count, blood chemistry, and lymphocyte subsets. We studied the Spearman correlation between baPWV and lymphocyte subsets and other variables. We further used multivariable stepwise linear regression analysis and the results showed that baPWV was significantly correlated with age, height, systolic blood pressure, and the level of T lymphocytes (CD3+CD45+) in hypertensive patients (β = 8.77, P = 0.006; β = -17.50, P = 0.001; β = 6.70, P = 0.002, and β = -7.093, P = 0.024, respectively). According to our findings, baPWV was independently and negatively correlated with the level of peripheral blood T lymphocytes in hypertensives, and infiltration of T lymphocytes into the vessels wall may be a key part of the immune mechanism of arteriosclerosis in hypertension.
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Affiliation(s)
- Ting Xu
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fangwen Zhou
- Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Chang Xu
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Benxi Central Hospital, Benxi, China
| | - Ailin Chen
- School of Information Systems & Technology Management, Business School, University of New South Wales, Sydney, NSW, Australia
| | - Shuaiwen Huang
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. .,Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Honglian Zhou
- Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Durmuş İ, Kalaycıoğlu E, Çetin M, Şahin HB, Kırış T. Exercise-Based Cardiac Rehabilitation Has a Strong Relationship with Mean Platelet Volume Reduction. Arq Bras Cardiol 2021; 116:434-440. [PMID: 33566933 PMCID: PMC8159561 DOI: 10.36660/abc.20190514] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 12/27/2019] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Mean platelet volume (MPV), which is a simple measure of platelet activation, has recently become an interesting topic in cardiovascular research. Exercise-based cardiac rehabilitation (CR) is a comprehensive intervention that decreases mortality-morbidity in patients with coronary artery disease (CAD). Studies on the effects of exercise on platelet activation have yielded conflicting results. OBJECTIVE The purpose of this study was to determine the effect of an exercise-based CR programs on MPV in patients with stable CAD. METHODS The sample was composed of 300 consecutive stable CAD patients. The patients were divided into two groups: CR group (n = 97) and non-CR group (n = 203). Blood analysis was performed. Point-Biserial correlation measures were performed to show correlation between MPV change and CR. A p value of <0.05 was considered statistically significant. RESULTS The decrease in MPV was greater in the CR group than in the non-CR group [(-1.10(-1.40-(-0.90)) vs. (-0.10 (-2.00-0.00)); p< 0.001]. ΔMPV had a positive correlation with Δ neutrophil (r = 0.326, p < 0.001), ΔTG (r = 0.439, p < 0.001), ΔLDL-c (r = 0.478, p < 0.001), ΔWBC (r = 0.412, p < 0.001), and ΔCRP (r = 0.572, p < 0.001). A significant correlation was found between ΔMPV% and CR (r=0.750, p<0.001). CONCLUSIONS We were able to show that exercise-based CR has a strong relationship with MPV reduction in patients with CAD. We consider that decreased platelet activation with exercise-based CR might play an important role in reducing thrombotic risk in patients with stable CAD. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).
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Affiliation(s)
- İsmet Durmuş
- University of Health Sciences Turkey , Ahi Evren Chest and Cardiovascular Surgery Education and Research Hospital , Trabzon - Turquia
| | - Ezgi Kalaycıoğlu
- University of Health Sciences Turkey , Ahi Evren Chest and Cardiovascular Surgery Education and Research Hospital , Trabzon - Turquia
| | - Mustafa Çetin
- Recep Tayyip Erdogan University, Faculty of Medicine , Rize - Turquia
| | - Hanife Baykal Şahin
- University of Health Sciences Turkey , Ahi Evren Chest and Cardiovascular Surgery Education and Research Hospital , Trabzon - Turquia
| | - Tuncay Kırış
- zmir Katip Çelebi University Atatürk Training and Research Hospital , Department of Cardiology , İzmir - Turquia
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Faria APD, Ritter AMV, Santa-Catharina A, Souza DP, Naseri EP, Bertolo MB, Pioli MR, Carvalho CC, Modolo R, Moreno H. Effects of Anti-TNF alpha Therapy on Blood Pressure in Resistant Hypertensive Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Study. Arq Bras Cardiol 2021; 116:443-451. [PMID: 33909773 PMCID: PMC8159563 DOI: 10.36660/abc.202190703] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 03/09/2020] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND The cytokine tumor necrosis factor-alpha (TNF-α) is elevated in resistant hypertension (RH), but the effects of a TNF-α inhibitor in this population is unknown. OBJECTIVE The aim of this trial was to evaluate whether a single dose of infliximab controlled by placebo acutely reduces blood pressure (BP) in RH subjects. METHODS A double-blind, placebo-controlled, crossover trial was conducted, and randomized RH subjects received either infliximab or placebo. The primary endpoint was the change in mean BP levels relative to the baseline immediately after the infusion obtained by continuously beat-to-beat non-invasive hemodynamic assessment. Secondary endpoints included changes in office, ambulatory and central BP measurements; endothelial function; and inflammatory biomarkers after 7 days. The level of significance accepted was alpha=0.05. RESULTS Ten RH subjects were enrolled. The primary endpoint analysis showed an acute decrease in mean BP values (mean of differences ± standard deviation = -6.3 ± 7.2 mmHg, p=0.02) from baseline, after the application of infliximab compared with placebo. Diastolic BP levels (-4.9 ± 5.5 mmHg, p=0.02), but not systolic BP levels (-9.4 ± 19.7 mmHg, p=0.16), lowered after infliximab infusion. No further significant differences were identified in either the other hemodynamic parameters or in secondary endpoints, except for TNF-α levels, which increased continuously after infliximab infusion. No adverse events were reported during the protocol. CONCLUSIONS A single-dose of infliximab decreased the mean and diastolic BP levels immediately after its infusion, when compared to the placebo in RH. The anti-TNF-α therapy was found to be safe and well-tolerated. The results of this proof-of-concept are hypothesis-generating and need to be further investigated. (Arq Bras Cardiol. 2021; 116(3):443-451).
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Affiliation(s)
| | | | | | - Débora P Souza
- Universidade Estadual de Campinas, Campinas, SP - Brasil
| | | | | | | | | | - Rodrigo Modolo
- Universidade Estadual de Campinas, Campinas, SP - Brasil
| | - Heitor Moreno
- Universidade Estadual de Campinas, Campinas, SP - Brasil
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Abstract
Arterial stiffness, a leading marker of risk in hypertension, can be measured at material or structural levels, with the latter combining effects of the geometry and composition of the wall, including intramural organization. Numerous studies have shown that structural stiffness predicts outcomes in models that adjust for conventional risk factors. Elastic arteries, nearer to the heart, are most sensitive to effects of blood pressure and age, major determinants of stiffness. Stiffness is usually considered as an index of vascular aging, wherein individuals excessively affected by risk factor exposure represent early vascular aging, whereas those resistant to risk factors represent supernormal vascular aging. Stiffness affects the function of the brain and kidneys by increasing pulsatile loads within their microvascular beds, and the heart by increasing left ventricular systolic load; excessive pressure pulsatility also decreases diastolic pressure, necessary for coronary perfusion. Stiffness promotes inward remodeling of small arteries, which increases resistance, blood pressure, and in turn, central artery stiffness, thus creating an insidious feedback loop. Chronic antihypertensive treatments can reduce stiffness beyond passive reductions due to decreased blood pressure. Preventive drugs, such as lipid-lowering drugs and antidiabetic drugs, have additional effects on stiffness, independent of pressure. Newer anti-inflammatory drugs also have blood pressure independent effects. Reduction of stiffness is expected to confer benefit beyond the lowering of pressure, although this hypothesis is not yet proven. We summarize different steps for making arterial stiffness measurement a keystone in hypertension management and cardiovascular prevention as a whole.
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Affiliation(s)
- Pierre Boutouyrie
- Faculté de Médecine, Université de Paris, INSERM U970, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, France (P.B.)
| | - Phil Chowienczyk
- King's College London British Heart Foundation Centre, Department of Clinical Pharmacology, St Thomas' Hospital, London, United Kingdom (P.C.)
| | - Jay D Humphrey
- Department of Biomedical Engineering and Vascular Biology and Therapeutics Program, Yale University, New Haven, CT (J.D.H.)
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Demir K, Avcı A, Ergulu Esmen S, Tuncez A, Yalcın MU, Yılmaz A, Yılmaz S, Altunkeser BB. Assessment of arterial stiffness and epicardial adipose tissue thickness in predicting the subclinical atherosclerosis in patients with ankylosing spondylitis. Clin Exp Hypertens 2020; 43:169-174. [PMID: 33028113 DOI: 10.1080/10641963.2020.1833025] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVE Atherosclerosis is a chronic, progressive, inflammatory disease. Recognition of subclinical atherosclerotic vascular changes before clinical manifestation in an asymptomatic population is important for risk stratification and optimal management, which finally leads to the prevention of cardiovascular disease. We aimed to determine the risk of premature subclinical atherosclerosis by evaluating epicardial adipose tissue thickness (EATT) and arterial stiffness parameters in patients with ankylosing spondylitis (AS). METHODS We performed a prospective study of 60 consecutive patients meeting modified New York criteria for AS compared to 60 controls matched for age and sex. Patients with traditional cardiovascular risk factors were excluded. Arterial stiffness parameters and EATT (examined via echocardiography) values of all patients and control groups were measured. RESULTS There was no difference between basal characteristic and echocardiographic parameters in patients with AS and in the control group. EATT and pulse wave velocity (PWV) were higher in the AS patients compared to the control group. EATT was 5.74 ± 1.22 mm and 4.91 ± 1.21 mm (p < .001) and PWV was 9.90 ± 0.98 m/s and 6.46 ± 0.83 m/s (p = .009) in the AS and control groups, respectively. Also, PWV was significantly correlated with EATT, age, and central blood pressure in patients with AS. CONCLUSIONS EATT and PWV, markers of atherosclerosis and cardiovascular disease, were significantly higher in patients with AS than the control group. In addition, in this study, it has been shown that there is a significant relationship between PWV and EATT in patients with AS.
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Affiliation(s)
- Kenan Demir
- Faculty of Medicine Cardiology Department, Selcuk University , Konya, Turkey
| | - Ahmet Avcı
- Faculty of Medicine Cardiology Department, Zonguldak Bülent Ecevit University , Zonguldak, Turkey
| | - Serpil Ergulu Esmen
- Department of Rheumatology, Konya Education Research Hospital , Konya, Turkey
| | - Abdullah Tuncez
- Faculty of Medicine Cardiology Department, Selcuk University , Konya, Turkey
| | | | - Ahmet Yılmaz
- , Department of Cardiology, Karaman State Hospital , Karaman, Turkey
| | - Sema Yılmaz
- Faculty of Medicine Rheumatology Department, Selcuk University , Konya, Turkey
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Yuan S, Carter P, Bruzelius M, Vithayathil M, Kar S, Mason AM, Lin A, Burgess S, Larsson SC. Effects of tumour necrosis factor on cardiovascular disease and cancer: A two-sample Mendelian randomization study. EBioMedicine 2020; 59:102956. [PMID: 32805626 PMCID: PMC7452586 DOI: 10.1016/j.ebiom.2020.102956] [Citation(s) in RCA: 86] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Revised: 07/26/2020] [Accepted: 08/03/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Tumour necrosis factor (TNF) inhibitors are used in the treatment of certain autoimmune diseases but given the role of TNF in tumour biology and atherosclerosis, such therapies may influence the risk of cancer and cardiovascular disease. We conducted a Mendelian randomization study to explore whether TNF levels are causally related to cardiovascular disease and cancer. METHODS Single-nucleotide polymorphisms associated with TNF levels at genome-wide significance were identified from a genome-wide association study of 30 912 European-ancestry individuals. Three TNF-associated single-nucleotide polymorphisms associated with higher risk of autoimmune diseases were used as instrumental variables. Summary-level data for 14 cardiovascular diseases, overall cancer and 14 site-specific cancers were obtained from UK Biobank and consortia. FINDINGS Genetically-predicted TNF levels were positively associated with coronary artery disease (odds ratio (OR) 2.25; 95% confidence interval (CI) 1.50, 3.37) and ischaemic stroke (OR 2.27; 95% CI 1.50, 3.43), and inversely associated with overall cancer (OR 0.54; 95% CI 0.42, 0.69), breast cancer (OR 0.51; 95% CI 0.39, 0.67), and colorectal cancer (OR 0.20; 95% CI 0.09, 0.45). There were suggestive associations of TNF with venous thromboembolism (OR 2.18; 95% CI 1.32, 3.59), endometrial cancer (OR 0.25; 95% CI 0.07, 0.94), and lung cancer (OR 0.45; 95% CI 0.21, 0.94). INTERPRETATION This study found evidence of causal associations of increased TNF levels with higher risk of common cardiovascular diseases and lower risk of overall and certain cancers.
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Affiliation(s)
- Shuai Yuan
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm 17177, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Paul Carter
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Maria Bruzelius
- Coagulation Unit, Department of Hematology, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | | | - Siddhartha Kar
- MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, United Kingdom
| | - Amy M Mason
- British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge and Cambridge University Hospitals, Cambridge, United Kingdom
| | - Ang Lin
- Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Stephen Burgess
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; MRC Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom
| | - Susanna C Larsson
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm 17177, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
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Wilson J, Webb AJS. Systolic Blood Pressure and Longitudinal Progression of Arterial Stiffness: A Quantitative Meta-Analysis. J Am Heart Assoc 2020; 9:e017804. [PMID: 32856498 PMCID: PMC7660776 DOI: 10.1161/jaha.120.017804] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background Arterial stiffness predicts the risk of cardiovascular events and all‐cause mortality and is associated with age and hypertension. However, the magnitude of the relationship between blood pressure (BP) and progression of arterial stiffness is unclear, limiting our understanding of how arterial stiffness mediates clinical effects of hypertension and planning of clinical trials. Methods and Results Medline and EMBASE were searched for prospective studies reporting linear models between baseline BP and progression of arterial stiffness, with and without adjustment for demographic characteristics and baseline stiffness. Standardized and unstandardized β coefficients for pulse wave velocity were combined by fixed and random effects meta‐analysis, weighted by the inverse variance. Of 566 fully reviewed articles from 30, 524 titles, 22 populations from 21 reports were included. In 9 cohorts, there were consistent, adjusted associations between baseline systolic BP and progression of arterial stiffness (11 781 patients; standardized β=0.041; 95% CI, 0.026–0.055; P<0.001; P value for heterogeneity=0.70), equivalent to a 1.14‐m/s increase in standard carotid‐femoral pulse wave velocity per decade per 20–mm Hg systolic BP, independent of age. Unstandardized, adjusted associations were similar (1762 patients; β=0.0047; 95% CI, 0.004–0.006; P<0.001; P value for heterogeneity=0.64), equivalent to a 0.94‐m/s increase per decade per 20–mm Hg systolic BP. In limited studies, standardized associations between mean BP and arterial stiffness progression were not significant and heterogeneous (913 patients; β=0.039; 95% CI, −0.008 to 0.086; P=0.11; P value for heterogeneity=0.03). Conclusions Baseline systolic BP was associated with a clinically important progression of arterial stiffness, independent of age, providing a reference for the potential effect of arterial stiffness in mediating changes in clinical outcomes associated with hypertension and providing a reference value to aid clinical trial design.
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Affiliation(s)
- Jack Wilson
- Wolfson Centre for Prevention of Stroke and Dementia University of Oxford United Kingdom
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38
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The risk of cardiovascular complications in inflammatory bowel disease. Clin Exp Med 2020; 20:481-491. [PMID: 32785793 PMCID: PMC7568702 DOI: 10.1007/s10238-020-00639-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Accepted: 06/15/2020] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic, relapsing disease of unknown etiology involving gastrointestinal tract. IBD comprises two main entities: ulcerative colitis and Crohn's disease. Several studies showed increased risk of cardiovascular complications in chronic inflammatory disorders, especially during IBD relapses. Endothelium plays a role in physiologic regulation of vascular tone, cell adhesion, migration and resistance to thrombosis. Also, its dysfunction is associated with increased risk of atherosclerosis development. There are several potential links between chronic IBD-related inflammatory processes and the risk of cardiovascular disease, but insight into pathogenetic pathways remains unclear. We present the current concepts and review of adult and pediatric studies on the risk of CVD in IBD.
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Abstract
PURPOSE OF REVIEW To review the data on the role of endothelial dysfunction and the impact of hypertension as a potent mediator of cardiovascular disease in patients with rheumatoid arthritis (RA). RECENT FINDINGS RA represents the most common autoimmune rheumatic disorder and is characterized by chronic systemic inflammation predisposing to cardiovascular complications. Cardiovascular mortality is increased among patients with RA and represents the leading cause of death. Although the exact prevalence is debated, hypertension is increased in RA. Hypertension acts synergistically with chronic inflammation and accounts, at least partially, for the increased cardiovascular morbidity in this group of patients. Endothelial dysfunction is considered a primary process in the pathogenesis of hypertension and cardiovascular diseases and contributes significantly to the development and progression of the associated micro- and macrovascular complications. Even though several studies in patients with RA have shown the presence of endothelial dysfunction with traditional methods, novel biochemical and vascular methods for the evaluation of endothelial dysfunction have been scarcely applied. In addition, it remains unclear whether and to which extent endothelial dysfunction in RA is present regardless of concomitant hypertension, even in well-controlled patients. Hypertension, endothelial dysfunction, and chronic systemic inflammation appear as a mutually reinforcing triad aggravating cardiovascular risk in patients with RA. Detection of endothelial dysfunction in patients with RA in the early stages further aiming at the development of novel therapeutic targets might contribute to prevention of cardiovascular complications and remains under investigation.
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40
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Baghdadi LR. Effect of methotrexate use on the development of type 2 diabetes in rheumatoid arthritis patients: A systematic review and meta-analysis. PLoS One 2020; 15:e0235637. [PMID: 32628710 PMCID: PMC7337336 DOI: 10.1371/journal.pone.0235637] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 06/18/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The high risk of cardiovascular disease is well recognized in rheumatoid arthritis. Type 2 diabetes also attributes to this increase in risk. Rheumatoid arthritis is a chronic inflammatory condition, which aggravates insulin resistance, placing the patients at a higher risk of type 2 diabetes and subsequent cardiovascular outcomes. Methotrexate treatment, as a gold standard anti-inflammatory drug in the treatment of rheumatoid arthritis has shown beneficial effects on cardiovascular health. However, its impact on type 2 diabetes is still unknown. OBJECTIVE To assess the strength of the association between exposure to methotrexate and the rate of development of type 2 diabetes in rheumatoid arthritis patients. METHODS All rheumatoid arthritis studies reporting the use of methotrexate as an exposure and type 2 diabetes as an outcome were searched until March 2020 using MEDLINE, Cochrane and Scopus databases. Studies were included if the diagnosis of rheumatoid arthritis was made according to current guidelines or by a rheumatologist, and if there was information about methotrexate exposure and the type 2 diabetes outcome. The author and an independent assessor evaluated the articles for eligibility. Meta-analyses combined relative risk estimates from each study where raw counts were available. RESULTS Sixteen studies reporting sufficient data for inclusion in the meta-analyses were identified. Methotrexate showed a promising effect on the risk of type 2 diabetes as this risk decreased in rheumatoid arthritis patients using methotrexate (Relative risk 0.48, 95% CI 0.16, 1.43). CONCLUSION Rheumatoid arthritis patients on methotrexate treatment had a lower risk of developing type 2 diabetes compared to rheumatoid arthritis patients not exposed to methotrexate. This finding highlights the need for future, randomized control trials to confirm the beneficial effect of methotrexate on type 2 diabetes in the rheumatoid arthritis population.
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Affiliation(s)
- Leena R. Baghdadi
- Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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41
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Kartal Öztürk G, Eşki A, Çelebi Çelik F, Conkar S, Gülen F, Demir E, Keskinoğlu A. Prospective evaluation of vascular changes in acute respiratory infections in children with cystic fibrosis. Turk J Med Sci 2020; 50:1007-1014. [PMID: 32421279 PMCID: PMC7379472 DOI: 10.3906/sag-2002-61] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Accepted: 05/16/2020] [Indexed: 01/15/2023] Open
Abstract
Background/aim Acute exacerbations and chronic inflammation are risk factors for cardiovascular disease (CVD) in cystic fibrosis (CF) patients. The aim of this study was to investigate the effects of acute exacerbation therapy on arterial stiffness in children with CF. Materials and methods Augmentation index (Aix) and pulse wave velocity (PWV) were measured before and after treatment and 1 month after the end of treatment in patients with acute exacerbation. The relationship between hemodynamic measurements and c-reactive protein (CRP) and pulmonary function tests (PFTs) was investigated. Results Measurements before and after treatment were evaluated in 27 patients and were repeated in 21 patients who were clinically stable 1 month following acute exacerbation. There was a significant decrease in CRP and an increase in spirometry parameters after treatment. While no significant difference was found between PWV (P = 0.33), a significant difference for Aix before (41.95 ± 12.96%) and after (30.95 ± 11.47%) treatment and before treatment and stable clinical condition (34.19 ± 14.36%) was obtained (P =0.00, and P =0.01, respectively). No significant difference in heart rate and other hemodynamic measurements was found. Pretreatment Aix is associated with poor clinical condition (PFTs, BMI, and clinical score) and systemic inflammation (CRP) (P <0.05). Conclusion The decrease of arterial stiffness (Aix) with acute exacerbation treatment in children with CF has been demonstrated. This result shows that systemic inflammation in CF may cause an increase in arterial stiffness and recurrent exacerbations may increase the risk of CVD.
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Affiliation(s)
- Gökçen Kartal Öztürk
- Department of Pediatrics, Division of Pulmonology, Faculty of Medicine, Ege University, İzmir, Turkey
| | - Aykut Eşki
- Department of Pediatrics, Division of Pulmonology, Faculty of Medicine, Ege University, İzmir, Turkey
| | - Figen Çelebi Çelik
- Department of Pediatrics, Division of Pulmonology, Faculty of Medicine, Ege University, İzmir, Turkey
| | - Seçil Conkar
- Department of Pediatrics, Division of Pediatric Nephrology, Faculty of Medicine, Ege University, İzmir, Turkey
| | - Figen Gülen
- Department of Pediatrics, Division of Pulmonology, Faculty of Medicine, Ege University, İzmir, Turkey
| | - Esen Demir
- Department of Pediatrics, Division of Pulmonology, Faculty of Medicine, Ege University, İzmir, Turkey
| | - Ahmet Keskinoğlu
- Department of Pediatrics, Division of Pediatric Nephrology, Faculty of Medicine, Ege University, İzmir, Turkey
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Kim SR, Lee SG, Kim SH, Kim JH, Choi E, Cho W, Rim JH, Hwang I, Lee CJ, Lee M, Oh CM, Jeon JY, Gee HY, Kim JH, Lee BW, Kang ES, Cha BS, Lee MS, Yu JW, Cho JW, Kim JS, Lee YH. SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease. Nat Commun 2020; 11:2127. [PMID: 32358544 PMCID: PMC7195385 DOI: 10.1038/s41467-020-15983-6] [Citation(s) in RCA: 338] [Impact Index Per Article: 67.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 04/02/2020] [Indexed: 11/19/2022] Open
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor's glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.
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Affiliation(s)
- So Ra Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Graduate School, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Department of Hospital Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, 16995, Republic of Korea
| | - Sang-Guk Lee
- Department of Laboratory Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Soo Hyun Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Jin Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Eunhye Choi
- Department of Laboratory Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Wonhee Cho
- Exercise Medicine Center for Diabetes and Cancer Patients, ICONS, Yonsei University, Seoul, 03722, Republic of Korea
| | - John Hoon Rim
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Department of Medicine, Physician-Scientist Program, Yonsei University Graduate School of Medicine, Seoul, 03722, Republic of Korea
| | - Inhwa Hwang
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Chan Joo Lee
- Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Minyoung Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Chang-Myung Oh
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea
| | - Justin Y Jeon
- Exercise Medicine Center for Diabetes and Cancer Patients, ICONS, Yonsei University, Seoul, 03722, Republic of Korea
| | - Heon Yung Gee
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Department of Medicine, Physician-Scientist Program, Yonsei University Graduate School of Medicine, Seoul, 03722, Republic of Korea
| | - Jeong-Ho Kim
- Department of Laboratory Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Byung-Wan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Graduate School, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Eun Seok Kang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Graduate School, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Bong-Soo Cha
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Graduate School, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Institute of Endocrine Research, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Myung-Shik Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Severance Biomedical Science Institute, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Je-Wook Yu
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
- Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Jin Won Cho
- Department of Systems Biology, Glycosylation Network Research Center, Yonsei University, Seoul, 03722, Republic of Korea
| | - Jung-Sun Kim
- Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
| | - Yong-Ho Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
- Graduate School, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
- Institute of Endocrine Research, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
- Department of Systems Biology, Glycosylation Network Research Center, Yonsei University, Seoul, 03722, Republic of Korea.
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Knowles L, Nadeem N, Chowienczyk PJ. Do anti-tumour necrosis factor-α biologics affect subclinical measures of atherosclerosis and arteriosclerosis? A systematic review. Br J Clin Pharmacol 2020; 86:837-851. [PMID: 31957052 DOI: 10.1111/bcp.14215] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 12/06/2019] [Accepted: 12/16/2019] [Indexed: 12/13/2022] Open
Abstract
AIMS Inflammatory cytokines, particularly tumour necrosis factor-α (TNFα), are thought to promote arterial disease through a variety of mechanisms leading to arteriosclerosis and atherosclerosis. We reviewed the existing evidence of the effect of anti-TNFα treatment on arteriosclerosis and atherosclerosis in chronic inflammatory disease. METHODS We performed a systematic review of studies examining effects of monoclonal antibodies against TNFα on subclinical measures of arteriosclerosis (arterial pulse wave velocity) and atherosclerosis (endothelial function measured by flow-mediated dilation or forearm blood flow responses to endothelium-dependent agonists, and common carotid intima-media thickness). RESULTS We identified 60 studies (of 854 potential studies identified using a systematic search) in which effects of anti-TNFα biologics on these measures were assessed in patients receiving anti-TNFα therapy for a clinical indication (usually an inflammatory disease such as an inflammatory arthritis, psoriasis or inflammatory bowel disease). Of these, only 6 were randomised clinical controlled trials. Whilst many observational studies and noncontrolled studies reported positive findings, positive finding were reported in only 1 of 6 randomised clinical controlled trials. CONCLUSIONS There is no strong evidence for an effect of anti-TNFα biologics on the subclinical measures of arteriosclerosis or atherosclerosis examined in this review. This does not exclude a positive effect of TNFα biologics on clinical outcomes through alternate pathways including those induced by remission of the primary inflammatory disease.
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Affiliation(s)
| | - Nida Nadeem
- King's College London, British Heart Foundation Centre, London, UK
| | - Philip J Chowienczyk
- Guy's and St Thomas's Foundation Trust, London, UK.,King's College London, British Heart Foundation Centre, London, UK
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Zanoli L, Ozturk K, Cappello M, Inserra G, Geraci G, Tuttolomondo A, Torres D, Pinto A, Duminuco A, Riguccio G, Aykan MB, Mulé G, Cottone S, Perna AF, Laurent S, Fatuzzo P, Castellino P, Boutouyrie P. Inflammation and Aortic Pulse Wave Velocity: A Multicenter Longitudinal Study in Patients With Inflammatory Bowel Disease. J Am Heart Assoc 2020; 8:e010942. [PMID: 30712441 PMCID: PMC6405571 DOI: 10.1161/jaha.118.010942] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Background Inflammatory bowel disease (IBD) is characterized by a low prevalence of traditional risk factors, an increased aortic pulse‐wave velocity (aPWV), and an excess of cardiovascular events. We have previously hypothesized that the cardiovascular risk excess reported in these patients could be explained by chronic inflammation. Here, we tested the hypothesis that chronic inflammation is responsible for the increased aPWV previously reported in IBD patients and that anti‐TNFa (anti‐tumor necrosis factor‐alpha) therapy reduce aPWV in these patients. Methods and Results This was a multicenter longitudinal study. We enrolled 334 patients: 82 patients with ulcerative colitis, 85 patients with Crohn disease, and 167 healthy control subjects matched for age, sex, and mean blood pressure, from 3 centers in Europe, and followed them for 4 years (range, 2.5–5.7 years). At baseline, IBD patients had higher aPWV than controls. IBD patients in remission and those treated with anti–TNFa during follow‐up experienced an aortic destiffening, whereas aPWV increased in those with active disease and those treated with salicylates (P=0.01). Disease duration (P=0.02) was associated with aortic stiffening as was, in patients with ulcerative colitis, high‐sensitivity C‐reactive protein during follow‐up (P=0.02). All these results were confirmed after adjustment for major confounders. Finally, the duration of anti–TNFa therapy was not associated with the magnitude of the reduction in aPWV at the end of follow‐up (P=0.85). Conclusions Long‐term anti–TNFa therapy reduces aPWV, an established surrogate measure of cardiovascular risk, in patients with IBD. This suggests that effective control of inflammation may reduce cardiovascular risk in these patients.
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Affiliation(s)
- Luca Zanoli
- 1 Nephrology Department of Clinical and Experimental Medicine University of Catania Italy
| | - Kadir Ozturk
- 2 Department of Gastroenterology Gulhane School of Medicine Etlik, Ankara Turkey
| | - Maria Cappello
- 3 DIBIMIS School of Medicine University of Palermo Italy
| | - Gaetano Inserra
- 4 Internal Medicine Department of Clinical and Experimental Medicine University of Catania Italy
| | - Giulio Geraci
- 5 Unit of Nephrology and Hypertension Department of Internal Medicine University of Palermo Italy
| | | | - Daniele Torres
- 3 DIBIMIS School of Medicine University of Palermo Italy
| | - Antonio Pinto
- 3 DIBIMIS School of Medicine University of Palermo Italy
| | - Andrea Duminuco
- 4 Internal Medicine Department of Clinical and Experimental Medicine University of Catania Italy
| | - Gaia Riguccio
- 4 Internal Medicine Department of Clinical and Experimental Medicine University of Catania Italy
| | - Musa B Aykan
- 6 Department of Internal Medicine Gulhane School of Medicine Etlik, Ankara Turkey
| | - Giuseppe Mulé
- 5 Unit of Nephrology and Hypertension Department of Internal Medicine University of Palermo Italy
| | - Santina Cottone
- 5 Unit of Nephrology and Hypertension Department of Internal Medicine University of Palermo Italy
| | - Alessandra F Perna
- 7 First Division of Nephrology Department of Cardiothoracic & Respiratory Sciences University of Campania "Luigi Vanvitelli" Naples Italy
| | - Stephane Laurent
- 8 Department of Pharmacology HEGP Université Paris Descartes AP-HP INSERM U970 Paris France
| | - Pasquale Fatuzzo
- 1 Nephrology Department of Clinical and Experimental Medicine University of Catania Italy
| | - Pietro Castellino
- 4 Internal Medicine Department of Clinical and Experimental Medicine University of Catania Italy
| | - Pierre Boutouyrie
- 8 Department of Pharmacology HEGP Université Paris Descartes AP-HP INSERM U970 Paris France
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Carbone F, Bonaventura A, Liberale L, Paolino S, Torre F, Dallegri F, Montecucco F, Cutolo M. Atherosclerosis in Rheumatoid Arthritis: Promoters and Opponents. Clin Rev Allergy Immunol 2020; 58:1-14. [PMID: 30259381 DOI: 10.1007/s12016-018-8714-z] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Substantial epidemiological data identified cardiovascular (CV) diseases as a main cause of mortality in patients with rheumatoid arthritis (RA). In light of this, RA patients may benefit from additional CV risk screening and more intensive prevention strategies. Nevertheless, current algorithms for CV risk stratification still remain tailored on general population and are burdened by a significant underestimation of CV risk in RA patients. Acute CV events in patients with RA are largely related to an accelerated atherosclerosis. As pathophysiological features of atherosclerosis overlap those occurring in the inflamed RA synovium, the understanding of those common pathways represents an urgent need and a leading challenge for CV prevention in patients with RA. Genetic background, metabolic status, gut microbiome, and systemic inflammation have been also suggested as additional key pro-atherosclerotic factors. The aim of this narrative review is to update the current knowledge about pathophysiology of atherogenesis in RA patients and potential anti-atherosclerotic effects of disease-modifying anti-rheumatic drugs.
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Affiliation(s)
- Federico Carbone
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Aldo Bonaventura
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Luca Liberale
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Center for Molecular Cardiology, University of Zürich, 12 Wagistrasse, 8952, Schlieren, Switzerland
| | - Sabrina Paolino
- Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, San Martino Polyclinic Hospital, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa, 10 Largo Benzi, 16132, Genoa, Italy
| | - Francesco Torre
- IRCCS Ospedale Policlinico San Martino Genoa, 10 Largo Benzi, 16132, Genoa, Italy
- Clinic of Emergency Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Franco Dallegri
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino Genoa-Italian Cardiovascular Network, 10 Largo Benzi, 16132, Genoa, Italy
| | - Fabrizio Montecucco
- IRCCS Ospedale Policlinico San Martino Genoa-Italian Cardiovascular Network, 10 Largo Benzi, 16132, Genoa, Italy
- First Clinic of Internal Medicine, Department of Internal Medicine and Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy
| | - Maurizio Cutolo
- IRCCS Ospedale Policlinico San Martino Genoa, 10 Largo Benzi, 16132, Genoa, Italy.
- Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Centre of Excellence for Biomedical Research (CEBR), University of Genoa, San Martino Polyclinic Hospital, Genoa, Italy.
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Azemi AK, Mokhtar SS, Rasool AHG. Clinacanthus nutans: Its potential against diabetic vascular diseases. BRAZ J PHARM SCI 2020. [DOI: 10.1590/s2175-97902020000118838] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Drakopoulou M, Soulaidopoulos S, Oikonomou G, Tousoulis D, Toutouzas K. Cardiovascular Effects of Biologic Disease-Modifying Anti-Rheumatic Drugs (DMARDs). Curr Vasc Pharmacol 2020; 18:488-506. [PMID: 32056527 DOI: 10.2174/1570161118666200214115532] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 10/22/2019] [Accepted: 10/22/2019] [Indexed: 01/07/2023]
Abstract
The risk of cardiovascular (CV) disease is increased among patients with systemic autoimmune rheumatic diseases and remains an underserved area of medical need. Although traditional risk factors for CV disease, such as hypertension, smoking, dyslipidemia and obesity contribute to endothelial dysfunction in rheumatoid arthritis (RA), they are not enough on their own to explain the observed excess CV risk. Rather, systemic inflammation seems to play a pivotal role in both disease states. Considering the inflammatory process in autoimmune diseases, scientific interest has focused on recently introduced biologic disease-modifying agents (bDMARDS) such as inhibitors of Tumor Necrosis Factor- α (ΤΝF-α), Interleukins -1 (IL-1) and -6 (IL-6). Despite the widespread use of bDMARDS in RA and other chronic autoimmune inflammatory diseases, their precise impact on CV disease and outcome remains to be elucidated, while prospective randomized control trials assessing their impact on hard CV endpoints are scarce. In this review, we summarize current knowledge concerning the effect of bDMARDs on CV outcome and on the risk of developing CV disease in patients with systemic autoimmune rheumatic diseases.
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Affiliation(s)
- Maria Drakopoulou
- First Department of Cardiology, Athens School of Medicine, Hippokration Hospital, Athens, Greece
| | - Stergios Soulaidopoulos
- First Department of Cardiology, Athens School of Medicine, Hippokration Hospital, Athens, Greece
| | - George Oikonomou
- First Department of Cardiology, Athens School of Medicine, Hippokration Hospital, Athens, Greece
| | - Dimitrios Tousoulis
- First Department of Cardiology, Athens School of Medicine, Hippokration Hospital, Athens, Greece
| | - Konstantinos Toutouzas
- First Department of Cardiology, Athens School of Medicine, Hippokration Hospital, Athens, Greece
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48
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Végh E, Kerekes G, Pusztai A, Hamar A, Szamosi S, Váncsa A, Bodoki L, Pogácsás L, Balázs F, Hodosi K, Domján A, Szántó S, Nagy Z, Szekanecz Z, Szűcs G. Effects of 1-year anti-TNF-α therapy on vascular function in rheumatoid arthritis and ankylosing spondylitis. Rheumatol Int 2019; 40:427-436. [DOI: 10.1007/s00296-019-04497-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Accepted: 12/10/2019] [Indexed: 12/28/2022]
Abstract
AbstractAccelerated atherosclerosis, increased cardiovascular morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Vascular function, clinical and laboratory markers and the effects of anti-TNF therapy were assessed in arthritides. Fifty-three 53 patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. A significant improvement of brachial artery FMD was observed after 6 months (p = 0.004). A tendency of FMD improvement was also observed after 12 months (p = 0.065). ccIMT did not change throughout the year. PWV significantly improved after 12 months (p = 0.034). Higher baseline ccIMT (p = 0.009) and PWV (p = 0.038) were associated with clinical non-response (cNR) versus response (cR) to biologics. Multiple analysis confirmed the association of baseline ccIMT with age (p = 0.003) and cNR (p = 0.009), as well as that of baseline PWV with age at diagnosis (p = 0.022) and current chest pain (p = 0.004). Treatment itself determined the 12-month changes in FMD (p = 0.020) and PWV (p = 0.007). In a mixed cohort of RA and AS patients, TNF inhibition improved or stabilized vascular pathophysiology. Inflammation may be associated with FMD, while, among others, cNR may influence vascular function.
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Choi H, Uceda DE, Dey AK, Mehta NN. Application of Non-invasive Imaging in Inflammatory Disease Conditions to Evaluate Subclinical Coronary Artery Disease. Curr Rheumatol Rep 2019; 22:1. [PMID: 31832865 DOI: 10.1007/s11926-019-0875-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE OF REVIEW Traditional risk models, such as the Framingham risk score, fail to capture the increased cardiovascular disease risk seen in patients with chronic inflammatory diseases. This review will cover imaging modalities and their emerging applications in assessing subclinical cardiovascular disease for both research and clinical care in patients with chronic inflammatory diseases. RECENT FINDINGS Multiple imaging modalities have been studied to assess for subclinical cardiovascular disease via functional/physiologic, inflammatory, and anatomic assessment in patients with chronic inflammatory diseases. The use of imaging to evaluate subclinical cardiovascular disease in patients with chronic inflammatory diseases has the potential to capture early sub-clinical atherosclerosis, to improve risk stratification of future cardiovascular events, and to guide effective disease management.
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Affiliation(s)
- Harry Choi
- National Heart, Lung, Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA
| | - Domingo E Uceda
- National Heart, Lung, Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA
| | - Amit K Dey
- National Heart, Lung, Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA
| | - Nehal N Mehta
- National Heart, Lung, Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
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50
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Zhang X, Lim SC, Tavintharan S, Yeoh LY, Sum CF, Ang K, Yeo D, Low S, Kumari N. Association of central arterial stiffness with the presence and severity of diabetic retinopathy in Asians with type 2 diabetes. Diab Vasc Dis Res 2019; 16:498-505. [PMID: 31046450 DOI: 10.1177/1479164119845904] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVE Arterial stiffness has been associated with diabetic retinopathy; however, the information is limited in Asians. We aim to examine the association of central arterial stiffness with the presence and severity of diabetic retinopathy in type 2 diabetes mellitus patients in Singapore. METHODS Arterial stiffness was estimated by carotid-femoral pulse wave velocity and augmentation index using applanation tonometry method. Digital colour fundus photographs from 1,203 patients were assessed for diabetic retinopathy. Diabetic retinopathy severity was categorized into non-proliferative diabetic retinopathy and proliferative diabetic retinopathy. Logistic regression model was used to evaluate the associations of diabetic retinopathy with pulse wave velocity and augmentation index. RESULTS Diabetic retinopathy was diagnosed in 391 (32.5%) patients, including 271 non-proliferative diabetic retinopathy and 108 proliferative diabetic retinopathy. Diabetic retinopathy have higher pulse wave velocity (11.2 ± 3.3 vs 9.5 ± 2.6 m/s, p < 0.001) and augmentation index (28.4 ± 9.4 vs 26.1 ± 10.6%, p < 0.001) than non-diabetic retinopathy. After multivariable adjustment, pulse wave velocity [odds ratio = 1.11 (95% confidence interval = 1.05-1.17), p < 0.001] and augmentation index [odds ratio = 1.03 (95% confidence interval = 1.01-1.04), p = 0.009] was associated with diabetic retinopathy. In severity analyses, pulse wave velocity was associated with non-proliferative diabetic retinopathy [odds ratio = 1.10 (95% confidence interval = 1.03-1.17), p = 0.002] and proliferative diabetic retinopathy [odds ratio = 1.15 (95% confidence interval = 1.06-1.25), p = 0.001] (p-trend < 0.001). Augmentation index showed significant associations with non-proliferative diabetic retinopathy [odds ratio = 1.02 (95% confidence interval = 1.01-1.04), p = 0.008], but not with proliferative diabetic retinopathy [odds ratio = 1.01 (95% confidence interval = 0.98-1.04), p = 0.36] (p-trend = 0.03). CONCLUSION Central arterial stiffness was associated with the presence and severity of diabetic retinopathy in type 2 diabetes mellitus patients, suggesting its etiologic implication in diabetic retinopathy.
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Affiliation(s)
- Xiao Zhang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Su Chi Lim
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore
- Department of Medicine, Khoo Teck Puat Hospital, Singapore
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Subramaniam Tavintharan
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore
- Department of Medicine, Khoo Teck Puat Hospital, Singapore
| | - Lee Ying Yeoh
- Department of Medicine, Khoo Teck Puat Hospital, Singapore
| | - Chee Fang Sum
- Diabetes Centre, Khoo Teck Puat Hospital, Singapore
- Department of Medicine, Khoo Teck Puat Hospital, Singapore
| | - Keven Ang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Darren Yeo
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Serena Low
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore
| | - Neelam Kumari
- Department of Ophthalmology and Visual Sciences, Khoo Teck Puat Hospital, Singapore
- Singapore Eye Research Institute, Singapore National Eye Centre, Singapore
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