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Wang X, Chen L, Wei J, Zheng H, Zhou N, Xu X, Deng X, Liu T, Zou Y. The immune system in cardiovascular diseases: from basic mechanisms to therapeutic implications. Signal Transduct Target Ther 2025; 10:166. [PMID: 40404619 DOI: 10.1038/s41392-025-02220-z] [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: 09/08/2024] [Revised: 12/22/2024] [Accepted: 03/20/2025] [Indexed: 05/24/2025] Open
Abstract
Immune system plays a crucial role in the physiological and pathological regulation of the cardiovascular system. The exploration history and milestones of immune system in cardiovascular diseases (CVDs) have evolved from the initial discovery of chronic inflammation in atherosclerosis to large-scale clinical studies confirming the importance of anti-inflammatory therapy in treating CVDs. This progress has been facilitated by advancements in various technological approaches, including multi-omics analysis (single-cell sequencing, spatial transcriptome et al.) and significant improvements in immunotherapy techniques such as chimeric antigen receptor (CAR)-T cell therapy. Both innate and adaptive immunity holds a pivotal role in CVDs, involving Toll-like receptor (TLR) signaling pathway, nucleotide-binding oligomerization domain-containing proteins 1 and 2 (NOD1/2) signaling pathway, inflammasome signaling pathway, RNA and DNA sensing signaling pathway, as well as antibody-mediated and complement-dependent systems. Meanwhile, immune responses are simultaneously regulated by multi-level regulations in CVDs, including epigenetics (DNA, RNA, protein) and other key signaling pathways in CVDs, interactions among immune cells, and interactions between immune and cardiac or vascular cells. Remarkably, based on the progress in basic research on immune responses in the cardiovascular system, significant advancements have also been made in pre-clinical and clinical studies of immunotherapy. This review provides an overview of the role of immune system in the cardiovascular system, providing in-depth insights into the physiological and pathological regulation of immune responses in various CVDs, highlighting the impact of multi-level regulation of immune responses in CVDs. Finally, we also discuss pre-clinical and clinical strategies targeting the immune system and translational implications in CVDs.
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Affiliation(s)
- Xiaoyan Wang
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
- State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
| | - Liming Chen
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China
- State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jianming Wei
- Central Diagnostics Laboratory, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands
| | - Hao Zheng
- Jiangsu Provincial Key Laboratory of Critical Care Medicine and Department of Critical Care Medicine, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, China
| | - Ning Zhou
- Department of Cardiovascular Medicine, Anzhen Hospital Affiliated to Capital Medical University, Beijing, China
| | - Xinjie Xu
- State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xin Deng
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China
- State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Tao Liu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine and Department of Critical Care Medicine, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, China.
- Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Jiangsu, Nanjing, China.
- State Key Laboratory of Respiratory Disease, Joint International Research Laboratory of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
| | - Yunzeng Zou
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
- State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
- Institutes of Advanced Medical Sciences and Huaihe Hospital, Henan University, Kaifeng, Henan, China.
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Mansoor T, Farrukh F, Khalid SN, Abramov D, Michos ED, Mehta A, Paul TK, Dani SS, Al Rifai M, Misra A, Nambi V, Virani SS, Minhas AMK. The future of hypertension pharmacotherapy: Ongoing and future clinical trials for hypertension. Curr Probl Cardiol 2025; 50:102922. [PMID: 39522662 DOI: 10.1016/j.cpcardiol.2024.102922] [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: 11/02/2024] [Accepted: 11/04/2024] [Indexed: 11/16/2024]
Abstract
Hypertension is among the most prevalent diagnoses across the world and increases the risk of many serious health problems, such as stroke, heart disease, and kidney disease. Pharmacological approaches to treat hypertension are often required and reduce blood pressure through mechanisms such as vasodilation, inhibition of the renin-angiotensin-aldosterone pathway, and increased urine output to reduce blood volume, among other mechanisms. Further research is ongoing to find novel pathways and mechanisms to treat hypertension, which we summarize in this review. We used clinicaltrials.gov to gather information about ongoing clinical trials of pharmacological hypertension therapy as of March 2024 and found 103 clinical trials that met our criteria. The interventions of these 103 clinical trials include novel and previously approved pharmacological and dietary supplement therapies for hypertension. We aim to use these clinical trials to provide insight into the future therapies and practices of hypertension treatment.
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Affiliation(s)
- Taha Mansoor
- Department of Internal Medicine, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, USA.
| | - Fatima Farrukh
- Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA
| | - Subaina N Khalid
- Department of Internal Medicine, SUNY Upstate Medical University, Syracruse, NY, USA
| | - Dmitry Abramov
- Division of Cardiology, Department of Medicine, Loma Linda University Health, Loma Linda, CA, USA
| | - Erin D Michos
- Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Anurag Mehta
- Division of Cardiology, Virginia Commonwealth University, Richmond, VA, USA
| | - Timir K Paul
- Department of Cardiovascular Sciences, University of Tennessee Health Science Center- Nashville, TN, USA
| | - Sourbha S Dani
- Division of Cardiology, Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, MA, USA
| | | | - Arunima Misra
- Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Vijay Nambi
- Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Section of Cardiovascular Research, Baylor College of Medicine, Houston, TX, USA; Michael E. DeBakey Veterans Affair Medical Center, Houston, TX, USA
| | - Salim S Virani
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Abdul Mannan Khan Minhas
- Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Section of Cardiovascular Research, Baylor College of Medicine, Houston, TX, USA
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3
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Akhtari S, Harvey PJ, Eder L. Cardio-Rheumatology Insights Into Hypertension: Intersection of Inflammation, Arteries, and Heart. Am J Hypertens 2024; 37:933-942. [PMID: 39056266 PMCID: PMC11565202 DOI: 10.1093/ajh/hpae098] [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: 06/19/2024] [Revised: 07/17/2024] [Accepted: 07/19/2024] [Indexed: 07/28/2024] Open
Abstract
There is an increased prevalence of atherosclerotic cardiovascular disease (ASCVD) in patients with inflammatory rheumatic diseases (IRD) including rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, and systemic sclerosis. The mechanism for the development of ASCVD in these conditions has been linked not only to a higher prevalence and undertreatment of traditional cardiovascular (CV) risk factors but importantly to chronic inflammation and a dysregulated immune system which contribute to impaired endothelial and microvascular function, factors that may contribute to accelerated atherosclerosis. Accurate ASCVD risk stratification and optimal risk management remain challenging in this population with many barriers that include lack of validated risk calculators, the remitting and relapsing nature of underlying disease, deleterious effect of medications used to manage rheumatic diseases, multimorbidity, decreased mobility due to joint pain, and lack of clarity about who bears the responsibility of performing CV risk assessment and management (rheumatologist vs. primary care provider vs. cardiologist). Despite recent advances in this field, there remain significant gaps in knowledge regarding the best diagnostic and management approach. The evolving field of Cardio-Rheumatology focuses on optimization of cardiovascular care and research in this patient population through collaboration and coordination of care between rheumatologists, cardiologists, radiologists, and primary care providers. This review aims to provide an overview of current state of knowledge about ASCVD risk stratification in patients with IRD, contributing factors including effect of medications, and review of the current recommendations for cardiovascular risk management in patients with inflammatory disease with a focus on hypertension as a key risk factor.
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Affiliation(s)
- Shadi Akhtari
- Division of Cardiology, Department of Medicine, Women’s College Hospital, Toronto, ON, Canada
- Women’s College Research Institute, Women’s College Hospital, Toronto, ON, Canada
- Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Paula J Harvey
- Division of Cardiology, Department of Medicine, Women’s College Hospital, Toronto, ON, Canada
- Women’s College Research Institute, Women’s College Hospital, Toronto, ON, Canada
- Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Lihi Eder
- Division of Rheumatology, Department of Medicine, Women’s College Hospital, Toronto, ON, Canada
- Women’s College Research Institute, Women’s College Hospital, Toronto, ON, Canada
- Department of Medicine, University of Toronto, Toronto, ON, Canada
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Shokoples BG, Paradis P, Schiffrin EL. Immunological insights into hypertension: unraveling triggers and potential therapeutic avenues. Hypertens Res 2024; 47:2115-2125. [PMID: 38778172 DOI: 10.1038/s41440-024-01731-6] [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: 01/27/2024] [Revised: 04/02/2024] [Accepted: 04/23/2024] [Indexed: 05/25/2024]
Abstract
Hypertension remains the leading cause of morbidity and mortality worldwide. Despite its prevalence, the development of novel antihypertensive therapies has only recently accelerated, with novel agents not yet commercialized, leaving a substantial proportion of individuals resistant to existing treatments. The intricate pathophysiology of hypertension is now understood to involve chronic low-grade inflammation, which places the immune system in the spotlight as a potential target for new therapeutics. This review explores the factors that initiate and sustain an immune response in hypertension, offering insights into potential targets for new treatments. Several factors contribute to immune activation in hypertension, including diet and damage-associated molecular pattern (DAMP) generation. Diets rich in fat or sodium can promote inflammation by inducing intestinal barrier dysfunction and triggering salt-sensitive receptors in T cells and dendritic cells. DAMPs, such as extracellular adenosine triphosphate and heat-shock protein 70, are released during episodes of increased blood pressure, contributing to immune cell activation and inflammation. Unconventional innate-like γδ T cells contribute to initiating and maintaining an immune response through their potential involvement in antigen presentation and regulating cytokine-mediated responses. Immunologic memory, sustained through the formation of effector memory T cells after exposure to hypertensive insults, likely contributes to maintaining an immune response in hypertension. When exposed to hypertensive insults, these memory cells are rapidly activated and contribute to elevated blood pressure and end-organ damage. Evidence from human hypertension, although limited, supports the relevance of distinct immune pathways in hypertension, and highlights the potential of targeted immune interventions in human hypertension. Diet and acute bouts of high blood pressure result in the release of dietary triggers, neoantigens, and damage-associated molecular patterns (DAMPs), which promote immune system activation. Elements such as lipopolysaccharides (LPS), sodium, heat-shock protein (HSP)70, extracellular adenosine triphosphate (eATP), and growth arrest-specific 6 (GAS6) promote activation of innate immune cells such as dendritic cells (DCs) and monocytes (Mo) through their respective receptors (toll-like receptor [TLR]4, amiloride-sensitive epithelial sodium channel [ENaC], TLR2/4, P2X7 receptor [P2RX7], and Axl) leading to costimulatory molecule expression and interleukin (IL)-1β and IL-23 production. The neoantigens HSP70 and isolevuglandins (IsoLGs) are presented to T cells by DCs and possibly γδ T cells, triggering T cell activation, IL-17 and interferon (IFN)-γ production, and the formation of T effector memory (TEM) cells in the kidney, perivascular adipose tissue, bone marrow, and spleen. Exposure of TEM cells to their cognate antigen or previous activating stimuli causes these cells rapid expansion and activation. Cumulatively, this inflammatory state contributes to hypertension and end-organ damage. The figure was created using images from smart.servier.com and is licensed under a Creative Commons Attribution 4.0 license (CC BY 4.0).
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Affiliation(s)
- Brandon G Shokoples
- Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research and McGill University, Montréal, QC, Canada
| | - Pierre Paradis
- Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research and McGill University, Montréal, QC, Canada
| | - Ernesto L Schiffrin
- Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research and McGill University, Montréal, QC, Canada.
- Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montréal, QC, Canada.
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Nguyen BA, Alexander MR, Harrison DG. Immune mechanisms in the pathophysiology of hypertension. Nat Rev Nephrol 2024; 20:530-540. [PMID: 38658669 PMCID: PMC12060254 DOI: 10.1038/s41581-024-00838-w] [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] [Accepted: 04/03/2024] [Indexed: 04/26/2024]
Abstract
Hypertension is a leading risk factor for morbidity and mortality worldwide. Despite current anti-hypertensive therapies, most individuals with hypertension fail to achieve adequate blood pressure control. Moreover, even with adequate control, a residual risk of cardiovascular events and associated organ damage remains. These findings suggest that current treatment modalities are not addressing a key element of the underlying pathology. Emerging evidence implicates immune cells as key mediators in the development and progression of hypertension. In this Review, we discuss our current understanding of the diverse roles of innate and adaptive immune cells in hypertension, highlighting key findings from human and rodent studies. We explore mechanisms by which these immune cells promote hypertensive pathophysiology, shedding light on their multifaceted involvement. In addition, we highlight advances in our understanding of autoimmunity, HIV and immune checkpoints that provide valuable insight into mechanisms of chronic and dysregulated inflammation in hypertension.
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Affiliation(s)
- Bianca A Nguyen
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA
| | - Matthew R Alexander
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA
- Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Vanderbilt Institute for Infection, Immunology and Inflammation, Nashville, TN, USA
| | - David G Harrison
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
- Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.
- Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
- Vanderbilt Institute for Infection, Immunology and Inflammation, Nashville, TN, USA.
- Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
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Zhang J, Liu P, Huang S, Chen Q, Wang X, Liu H. Association between rheumatoid arthritis and serum vitamin C levels in Adults: Based on the National health and Nutrition Examination survey database. Prev Med Rep 2024; 44:102793. [PMID: 38979480 PMCID: PMC11228779 DOI: 10.1016/j.pmedr.2024.102793] [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: 07/03/2023] [Revised: 06/06/2024] [Accepted: 06/06/2024] [Indexed: 07/10/2024] Open
Abstract
This study attempted to investigate relationship between rheumatoid arthritis and serum vitamin C levels using data from National Health and Nutrition Examination Survey (NHANES). The NHANES database aims to collect health, nutrition, biological, and behavioral data from a nationally representative sample of the population. This study utilizes NHANES data from three cycles: 2003-2004, 2005-2006, and 2017-2018, extracting data on the prevalence of rheumatoid arthritis and serum vitamin C levels. A generalized linear model is used to evaluate the association between the two. A total of 12,665 participants were included in the final analysis. Serum vitamin C levels were significantly higher in the non-rheumatoid arthritis group compared to the rheumatoid arthritis group (0.63 vs. 0.59, P = 0.042). Generalized linear model analysis showed that higher serum vitamin C levels were associated with a decreased risk of rheumatoid arthritis (OR = 0.62, 95 %CI: 0.40-0.98, P = 0.034). Stratified analysis revealed a significant interaction between non-hypertensive individuals and rheumatoid arthritis with serum vitamin C levels (P < 0.05). After adjusting for confounding factors, serum vitamin C levels remained significantly associated with rheumatoid arthritis in all models (P < 0.05). Restricted cubic spline results indicated that serum vitamin C levels above 0.95 mg/dL could help prevent rheumatoid arthritis. Increasing dietary vitamin C intake through supplementation was found to raise serum vitamin C levels. There was a significant association between rheumatoid arthritis and serum vitamin C levels, indicating that high levels of serum vitamin C may be a protective factor against rheumatoid arthritis.
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Affiliation(s)
- Jing Zhang
- Department of Rheumatology and Immunology, Xi'an No. 5 Hospital, No.112 XiGuanZhengJie, LianHu District, Xi'an City, Shaanxi Province 710082, China
| | - Pu Liu
- Department of rheumatism and Immunology, The First Affiliated Hospital of Xian Medical University, Xi'an City, Shaanxi Province 710077, China
| | - Sirou Huang
- Department of rheumatism and Immunology, The First Affiliated Hospital of Xian Medical University, Xi'an City, Shaanxi Province 710077, China
| | - Qingping Chen
- Department of Rheumatology and Immunology, Xi'an No. 5 Hospital, No.112 XiGuanZhengJie, LianHu District, Xi'an City, Shaanxi Province 710082, China
| | - Xiaoyuan Wang
- Department of Rheumatism and Immunology, Second Hospital of Lanzhou University, Lanzhou City, Gansu Province 730030, China
| | - Hua Liu
- Department of Rheumatology and Immunology, Xi'an No. 5 Hospital, No.112 XiGuanZhengJie, LianHu District, Xi'an City, Shaanxi Province 710082, China
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Guzik TJ, Nosalski R, Maffia P, Drummond GR. Immune and inflammatory mechanisms in hypertension. Nat Rev Cardiol 2024; 21:396-416. [PMID: 38172242 DOI: 10.1038/s41569-023-00964-1] [Citation(s) in RCA: 74] [Impact Index Per Article: 74.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/20/2023] [Indexed: 01/05/2024]
Abstract
Hypertension is a global health problem, with >1.3 billion individuals with high blood pressure worldwide. In this Review, we present an inflammatory paradigm for hypertension, emphasizing the crucial roles of immune cells, cytokines and chemokines in disease initiation and progression. T cells, monocytes, macrophages, dendritic cells, B cells and natural killer cells are all implicated in hypertension. Neoantigens, the NLRP3 inflammasome and increased sympathetic outflow, as well as cytokines (including IL-6, IL-7, IL-15, IL-18 and IL-21) and a high-salt environment, can contribute to immune activation in hypertension. The activated immune cells migrate to target organs such as arteries (especially the perivascular fat and adventitia), kidneys, the heart and the brain, where they release effector cytokines that elevate blood pressure and cause vascular remodelling, renal damage, cardiac hypertrophy, cognitive impairment and dementia. IL-17 secreted by CD4+ T helper 17 cells and γδ T cells, and interferon-γ and tumour necrosis factor secreted by immunosenescent CD8+ T cells, exert crucial effector roles in hypertension, whereas IL-10 and regulatory T cells are protective. Effector mediators impair nitric oxide bioavailability, leading to endothelial dysfunction and increased vascular contractility. Inflammatory effector mediators also alter renal sodium and water balance and promote renal fibrosis. These mechanisms link hypertension with obesity, autoimmunity, periodontitis and COVID-19. A comprehensive understanding of the immune and inflammatory mechanisms of hypertension is crucial for safely and effectively translating the findings to clinical practice.
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Affiliation(s)
- Tomasz J Guzik
- Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, UK.
- Department of Medicine and Omicron Medical Genomics Laboratory, Jagiellonian University, Collegium Medicum, Kraków, Poland.
- Africa-Europe Cluster of Research Excellence (CoRE) in Non-Communicable Diseases & Multimorbidity, African Research Universities Alliance ARUA & The Guild, Glasgow, UK.
| | - Ryszard Nosalski
- Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, UK
| | - Pasquale Maffia
- Africa-Europe Cluster of Research Excellence (CoRE) in Non-Communicable Diseases & Multimorbidity, African Research Universities Alliance ARUA & The Guild, Glasgow, UK
- School of Infection & Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Grant R Drummond
- Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Melbourne, Victoria, Australia
- Centre for Cardiovascular Biology and Disease Research, La Trobe University, Melbourne, Victoria, Australia
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Miyauchi H, Geisberger S, Luft FC, Wilck N, Stegbauer J, Wiig H, Dechend R, Jantsch J, Kleinewietfeld M, Kempa S, Müller DN. Sodium as an Important Regulator of Immunometabolism. Hypertension 2024; 81:426-435. [PMID: 37675565 PMCID: PMC10863658 DOI: 10.1161/hypertensionaha.123.19489] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/08/2023]
Abstract
Salt sensitivity concerns blood pressure alterations after a change in salt intake (sodium chloride). The heart is a pump, and vessels are tubes; sodium can affect both. A high salt intake increases cardiac output, promotes vascular dysfunction and capillary rarefaction, and chronically leads to increased systemic vascular resistance. More recent findings suggest that sodium also acts as an important second messenger regulating energy metabolism and cellular functions. Besides endothelial cells and fibroblasts, sodium also affects innate and adaptive immunometabolism, immune cell function, and influences certain microbes and microbiota-derived metabolites. We propose the idea that the definition of salt sensitivity should be expanded beyond high blood pressure to cellular and molecular salt sensitivity.
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Affiliation(s)
- Hidetaka Miyauchi
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.M., S.G., F.C.L., N.W., R.D., S.K., D.N.M.)
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, Germany (H.M., F.C.L., N.W., R.D., D.N.M.)
- Experimental and Clinical Research Center, a joint cooperation of Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany (H.M., F.C.L., N.W., R.D., D.N.M.)
- German Centre for Cardiovascular Research, Partner Site Berlin, Germany (H.M., N.W., R.D., D.N.M.)
| | - Sabrina Geisberger
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.M., S.G., F.C.L., N.W., R.D., S.K., D.N.M.)
| | - Friedrich C. Luft
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.M., S.G., F.C.L., N.W., R.D., S.K., D.N.M.)
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, Germany (H.M., F.C.L., N.W., R.D., D.N.M.)
- Experimental and Clinical Research Center, a joint cooperation of Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany (H.M., F.C.L., N.W., R.D., D.N.M.)
| | - Nicola Wilck
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.M., S.G., F.C.L., N.W., R.D., S.K., D.N.M.)
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, Germany (H.M., F.C.L., N.W., R.D., D.N.M.)
- Experimental and Clinical Research Center, a joint cooperation of Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany (H.M., F.C.L., N.W., R.D., D.N.M.)
- German Centre for Cardiovascular Research, Partner Site Berlin, Germany (H.M., N.W., R.D., D.N.M.)
| | - Johannes Stegbauer
- Department of Nephrology, Faculty of Medicine, University Hospital, Heinrich-Heine-University, Düsseldorf, Germany (J.S.)
- CARID, Cardiovascular Research Institute Düsseldorf, Medical Faculty and University Hospital, Düsseldorf, Germany (J.S.)
| | - Helge Wiig
- Department of Biomedicine, University of Bergen, Norway (H.W.)
| | - Ralf Dechend
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.M., S.G., F.C.L., N.W., R.D., S.K., D.N.M.)
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, Germany (H.M., F.C.L., N.W., R.D., D.N.M.)
- Experimental and Clinical Research Center, a joint cooperation of Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany (H.M., F.C.L., N.W., R.D., D.N.M.)
- German Centre for Cardiovascular Research, Partner Site Berlin, Germany (H.M., N.W., R.D., D.N.M.)
- HELIOS Clinic, Department of Cardiology and Nephrology, Berlin, Germany (R.D.)
| | - Jonathan Jantsch
- Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg and University of Regensburg, Germany (J.J.)
- Institute for Medical Microbiology, Immunology, and Hygiene, and Center for Molecular Medicine Cologne, University Hospital Cologne and Faculty of Medicine, University of Cologne, Germany (J.J.)
| | - Markus Kleinewietfeld
- VIB Laboratory of Translational Immunomodulation, VIB Center for Inflammation Research, Hasselt University, Diepenbeek, Belgium (M.K.)
- Department of Immunology, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium (M.K.)
- University Multiple Sclerosis Center, Hasselt University/Campus Diepenbeek, Belgium (M.K.)
| | - Stefan Kempa
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.M., S.G., F.C.L., N.W., R.D., S.K., D.N.M.)
| | - Dominik N. Müller
- Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (H.M., S.G., F.C.L., N.W., R.D., S.K., D.N.M.)
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, Germany (H.M., F.C.L., N.W., R.D., D.N.M.)
- Experimental and Clinical Research Center, a joint cooperation of Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Germany (H.M., F.C.L., N.W., R.D., D.N.M.)
- German Centre for Cardiovascular Research, Partner Site Berlin, Germany (H.M., N.W., R.D., D.N.M.)
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9
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Lu Y, Luo Q, Liu Y, Wang H. Relationships between inflammation markers and the risk of hypertension in primary Sjögren's syndrome: A retrospective cohort study. Mod Rheumatol 2024; 34:369-375. [PMID: 36976576 DOI: 10.1093/mr/road032] [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: 12/23/2022] [Revised: 03/01/2023] [Accepted: 03/20/2023] [Indexed: 03/29/2023]
Abstract
OBJECTIVES The association of inflammation markers with hypertension (HTN) in primary Sjögren's syndrome (pSS) remains controversial. We aimed to investigate whether inflammation markers are at increased risk of developing HTN in pSS patients. METHODS A retrospective cohort study included pSS patients (n = 380) between May 2011 and May 2020 from the Third People's Hospital of Chengdu. Multivariable Cox regression analyses were used to estimate hazard ratios (HRs) of the potential inflammation markers for pSS-HTN. Subsequently, the dose-response relationships were also used. RESULTS Out of 380 pSS patients, 171 (45%) developed HTN, and the median follow-up period was 4.16 years. Univariable Cox regression analysis showed that the erythrocyte sedimentation rate (ESR) and neutrophils were significantly associated with the incident HTN (P < 0.05). After adjustment for covariates, this association between ESR (adjusted HR 1.017, 95%CI: 1.005-1.027, P = .003), neutrophils (adjusted HR 1.356, 95%CI: 1.113-1.653, P = .003), and HTN remained significant. The dose-effect relationship was also found between ESR, neutrophils, and HTN (P = .001). CONCLUSIONS Inflammation markers may play an important role in the incident HTN in pSS.
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Affiliation(s)
- Yan Lu
- Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, Sichuan, China
- Department of Geriatrics, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Qiang Luo
- Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, Sichuan, China
- The Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, China
| | - Yaping Liu
- Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, Sichuan, China
- Department of Geriatrics, North Sichuan Medical College, Nanchong, Sichuan, China
| | - Han Wang
- Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, Sichuan, China
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10
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de Luna TA, Rezende DAN, de Brito LC, Fecchio RY, Lima FR, de Sá Pinto AL, de Medeiros Ribeiro AC, Bonfiglioli KR, Gualano B, Roschel H, Peçanha T. A single session of aerobic exercise reduces systolic blood pressure at rest and in response to stress in women with rheumatoid arthritis and hypertension. J Hum Hypertens 2024; 38:168-176. [PMID: 37857757 PMCID: PMC10844091 DOI: 10.1038/s41371-023-00869-z] [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: 04/10/2023] [Revised: 09/15/2023] [Accepted: 09/26/2023] [Indexed: 10/21/2023]
Abstract
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by increased risk of cardiovascular disease and hypertension (HT). A single session of aerobic exercise may reduce blood pressure (BP) in different clinical groups; however, little is known about the acute effects of exercise on BP in RA patients. This is a randomized controlled crossover study that assessed the effects of a single session of aerobic exercise on resting BP, on BP responses to stressful stimuli, and on 24-h BP in women with RA and HT. Twenty women with RA and HT (53 ± 10 years) undertook sessions of 30-min treadmill exercise (50% VO2max) or control (no exercise) in a crossover fashion. Before and after the sessions, BP was measured at rest, and in response to the Stroop-Color Word Test (SCWT), the Cold Pressor Test (CPT), and an isometric handgrip test. After the sessions, participants were also fitted with an ambulatory BP monitor for the assessment of 24-h BP. A single session of exercise reduced resting systolic BP (SBP) (-5 ± 9 mmHg; p < 0.05), and reduced SBP response to the SCWT (-7 ± 14 mmHg; p < 0.05), and to the CPT (-5 ± 11 mmHg; p < 0.05). Exercise did not reduce resting diastolic BP (DBP), BP responses to the isometric handgrip test or 24-h BP. In conclusion, a single session of aerobic exercise reduced SBP at rest and in response to stressful stimuli in hypertensive women with RA. These results support the use of exercise as a strategy for controlling HT and, hence, reducing cardiovascular risk in women with RA.Clinical Trial Registration: This study registered at the Brazilian Clinical Trials ( https://ensaiosclinicos.gov.br/rg/RBR-867k9g ) at 12/13/2019.
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Affiliation(s)
- Tatiane Almeida de Luna
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
- Laboratory of Assessment and Conditioning in Rheumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Diego Augusto Nunes Rezende
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
- Laboratory of Assessment and Conditioning in Rheumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Leandro Campos de Brito
- Exercise Hemodynamic Laboratory, School of Physical Education and Sport, University of São Paulo, Sao Paulo, SP, Brazil
- Applied Chronobiology and Exercise Physiology, School of Arts, Sciences and Humanities, University of São Paulo, Sao Paulo, SP, Brazil
- Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR, USA
| | - Rafael Yokoyama Fecchio
- Exercise Hemodynamic Laboratory, School of Physical Education and Sport, University of São Paulo, Sao Paulo, SP, Brazil
| | - Fernanda Rodrigues Lima
- Laboratory of Assessment and Conditioning in Rheumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Ana Lúcia de Sá Pinto
- Laboratory of Assessment and Conditioning in Rheumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Ana Cristina de Medeiros Ribeiro
- Rheumatology Division, Hospital das Clínicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Karina Rossi Bonfiglioli
- Rheumatology Division, Hospital das Clínicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Bruno Gualano
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
- Laboratory of Assessment and Conditioning in Rheumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Hamilton Roschel
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
- Laboratory of Assessment and Conditioning in Rheumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
| | - Tiago Peçanha
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
- Laboratory of Assessment and Conditioning in Rheumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
- Department of Sport and Exercise Sciences, Manchester Metropolitan University Institute of Sport, Manchester Metropolitan University, Manchester, UK.
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11
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Luo Q, Zhang Y, Yang X, Qin L, Wang H. Hypertension in connective tissue disease. J Hum Hypertens 2024; 38:19-28. [PMID: 35505225 DOI: 10.1038/s41371-022-00696-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 02/23/2022] [Accepted: 04/12/2022] [Indexed: 11/10/2022]
Abstract
It is well documented that connective tissue disease (CTD) is a type of autoimmune disease characterized by chronic inflammation, which can occur across various organ systems throughout the whole body. Although the clinical manifestations of CTD are different, studies have shown that different CTD diseases have similar pathogenesis, implying that different CTD diseases may have similar clinical outcomes. Recent population-based studies have demonstrated an increased risk of cardiovascular disease (CVD) in patients with CTD compared with the control group, which is partially attributed to traditional cardiovascular risk factors, such as hypertension (HT), and that controlling the patients' blood pressure (BP) still constitutes one of the most effective means to prevent CVD. Although many studies have shown that the prevalence of HT in patients with CTD is higher than that in the general population, there is a lack of adequate data on the possible pathogenesis of HT. Also, the factors that promote the rise of BP, especially the relationship between connective tissue disease- hypertension (CTD-HT) and traditional cardiovascular risk factors (aging, sex, race, dyslipidemia, diabetes mellitus, smoking, obesity, etc.), have not been fully confirmed. In this review, we explore the mechanisms that might lead to elevated BP in patients with CTD and the factors that contribute to elevated BP and the management of CTD-HT, and we focus on whether traditional cardiovascular risk factors, the disease, and the presence of related therapeutic drugs are associated with an increased risk of HT in patients with CTD.
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Affiliation(s)
- Qiang Luo
- Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, 82 Qinglong St., Chengdu, Sichuan, China
| | - Yiwen Zhang
- Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, 82 Qinglong St., Chengdu, Sichuan, China
| | - Xiaoqian Yang
- Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, 82 Qinglong St., Chengdu, Sichuan, China
| | - Li Qin
- Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, 82 Qinglong St., Chengdu, Sichuan, China
| | - Han Wang
- Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, 82 Qinglong St., Chengdu, Sichuan, China.
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12
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Bedeković D, Kirner D, Bošnjak I, Kibel A, Šarić S, Novak S, Prus V. The Influence of Rheumatoid Arthritis and Osteoarthritis on the Occurrence of Arterial Hypertension: An 8-Year Prospective Clinical Observational Cohort Study. J Clin Med 2023; 12:7158. [PMID: 38002770 PMCID: PMC10672072 DOI: 10.3390/jcm12227158] [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: 10/09/2023] [Revised: 11/16/2023] [Accepted: 11/16/2023] [Indexed: 11/26/2023] Open
Abstract
Rheumatoid arthritis (RA) increases the risk of cardiovascular mortality and morbidity, including a 50-60% increased risk of cardiovascular disease (CVD). Arterial hypertension (HT) is considered the major contributing risk factor for CVD development in RA patients. In this investigation, we compared the incidence and prevalence of HT between RA and osteoarthritis (OA) and the influence of HT on CVD development in CVD-naive patients in both groups. This was a prospective clinical cohort investigation with an 8-year follow-up period. A total of 201 participants, 124 with RA (investigation group) and 77 with OA (control group), without diagnosed CVD or symptomatic heart failure were included. After selection according to inclusion and exclusion criteria, both groups underwent initial and final visits, and the investigation group underwent annual visits to assess disease activity. Case report forms were completed for each visit. The obtained data were analyzed by a statistician. No difference in the incidence or prevalence of HT was found between the investigation and control groups. No difference in the prevalence of HT was reported between the study groups and age-standardized data from the general population. The investigation group had a higher incidence of CVD than the control group. RA participants with long-term remission had a marginally lower HT prevalence. Although previous studies reported a higher HT prevalence in RA than in OA and the general population, our findings did not support this. The RA group had a higher incidence of CVD, but it is possible that optimal disease control with long-term remission could reduce HT incidence and prevalence while also having beneficial effects on other cardiovascular risk factors (CV) and, consequently, CVD occurrence.
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Affiliation(s)
- Dražen Bedeković
- Department of Cardiovascular Diseases, Internal Medicine Clinic, University Hospital Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (D.B.); (D.K.); (A.K.); (S.Š.)
- Faculty of Medicine Osijek, Department of Internal Medicine, J. J. Strossmayer University, J. Huttlera 4, 31000 Osijek, Croatia
| | - Damir Kirner
- Department of Cardiovascular Diseases, Internal Medicine Clinic, University Hospital Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (D.B.); (D.K.); (A.K.); (S.Š.)
- Faculty of Medicine Osijek, Department of Internal Medicine, J. J. Strossmayer University, J. Huttlera 4, 31000 Osijek, Croatia
| | - Ivica Bošnjak
- Department of Cardiovascular Diseases, Internal Medicine Clinic, University Hospital Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (D.B.); (D.K.); (A.K.); (S.Š.)
| | - Aleksandar Kibel
- Department of Cardiovascular Diseases, Internal Medicine Clinic, University Hospital Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (D.B.); (D.K.); (A.K.); (S.Š.)
- Faculty of Medicine Osijek, Department of Physiology and Immunology, J. J. Strossmayer University, J. Huttlera 4, 31000 Osijek, Croatia
- Scientific Centre of Excellence for Personalized Health Care, J. J. Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia
| | - Sandra Šarić
- Department of Cardiovascular Diseases, Internal Medicine Clinic, University Hospital Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (D.B.); (D.K.); (A.K.); (S.Š.)
- Faculty of Medicine Osijek, Department of Internal Medicine, J. J. Strossmayer University, J. Huttlera 4, 31000 Osijek, Croatia
| | - Srđan Novak
- Department of Rheumatology and Clinical Immunology, University Hospital Rijeka, 51000 Rijeka, Croatia;
- Faculty of Medicine Rijeka, Department of Internal Medicine, University of Rijeka, Braće Branchetta 20/1, 51000 Rijeka, Croatia
| | - Višnja Prus
- Department of Rheumatology and Clinical Immunology, Internal Medicine Clinic, University Hospital Osijek J. Huttlera 4, 31000 Osijek, Croatia;
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13
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Copur S, Peltek IB, Mutlu A, Tanriover C, Kanbay M. A new immune disease: systemic hypertension. Clin Kidney J 2023; 16:1403-1419. [PMID: 37664577 PMCID: PMC10469084 DOI: 10.1093/ckj/sfad059] [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: 03/05/2023] [Indexed: 09/05/2023] Open
Abstract
Systemic hypertension is the most common medical comorbidity affecting the adult population globally, with multiple associated outcomes including cerebrovascular diseases, cardiovascular diseases, vascular calcification, chronic kidney disease, metabolic syndrome and mortality. Despite advancements in the therapeutic field approximately one in every five adult patients with hypertension is classified as having treatment-resistant hypertension, indicating the need for studies to provide better understanding of the underlying pathophysiology and the need for more therapeutic targets. Recent pre-clinical studies have demonstrated the role of the innate and adaptive immune system including various cell types and cytokines in the pathophysiology of hypertension. Moreover, pre-clinical studies have indicated the potential beneficial effects of immunosuppressant medications in the control of hypertension. Nevertheless, it is unclear whether such pathophysiological mechanisms and therapeutic alternatives are applicable to human subjects, while this area of research is undoubtedly a rapidly growing field.
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Affiliation(s)
- Sidar Copur
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Ibrahim B Peltek
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Ali Mutlu
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Cem Tanriover
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Mehmet Kanbay
- Department of Medicine, Section of Nephrology, Koc University School of Medicine, Istanbul, Turkey
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14
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Daidone M, Del Cuore A, Casuccio A, Di Chiara T, Guggino G, Di Raimondo D, Puleo MG, Ferrante A, Scaglione R, Pinto A, Tuttolomondo A. Vascular health in subjects with rheumatoid arthritis: assessment of endothelial function indices and serum biomarkers of vascular damage. Intern Emerg Med 2023; 18:467-475. [PMID: 36692587 DOI: 10.1007/s11739-023-03192-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 01/02/2023] [Indexed: 01/25/2023]
Abstract
BACKGROUND The cardiovascular risk (CVD) in patients with rheumatoid arthritis (RA) is 1.5-2 times higher than that in individuals of the same age and sex. AIMS To analyse the degree of endothelial dysfunction, the atherogenic immunoinflammatory serum background and the relationships among some vascular indices, cardiovascular comorbidities, and cognitive performance in subjects with RA. PATIENTS AND METHODS All consecutive patients with a rheumatoid arthritis diagnosis admitted to the Rheumatology Ward of "Policlinico Paolo Giaccone" Hospital of Palermo were enrolled from July 2019 to September 2020. We evaluated our patients' cognitive functions by administering the Mini-Mental State Examination (MMSE). Reactive Hyperaemia Index (RHI) was evaluated for assessment of endothelial function. Serum levels of angiopoietin 2, osteopontin and pentraxin 3 were assessed by blood collection. RESULTS Fifty-eight consecutive patients with RA and 40 control subjects were analysed. RA patients showed significantly lower mean RHI values, significantly higher mean Augmentation Index (AIX) values and significantly lower mean Mini-Mental State Examination (MMSE) score values than the control group. Patients with rheumatoid arthritis also showed higher mean serum values of pentraxin 3 and angiopoietin 2 than healthy controls. Multivariate logistic regression analysis showed a significant association between pentraxin 3 and angiopoietin 2 and the presence of RA. DISCUSSION Angiopoietin 2 and pentraxin 3 could be considered surrogate biomarkers of endothelial activation and vascular disease, as they could play an essential role in the regulation of endothelial integrity and inflammation.
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Affiliation(s)
- Mario Daidone
- U.O. C di Medicina Interna con Stroke Care, Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", (ProMise), Università degli Studi di Palermo, Piazza delle Cliniche N.2, 90127, Palermo, Italy
- Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro"(ProMise), Università degli Studi di Palermo, Palermo, Italy
| | - Alessandro Del Cuore
- U.O. C di Medicina Interna con Stroke Care, Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", (ProMise), Università degli Studi di Palermo, Piazza delle Cliniche N.2, 90127, Palermo, Italy
- Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro"(ProMise), Università degli Studi di Palermo, Palermo, Italy
| | - Alessandra Casuccio
- Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro"(ProMise), Università degli Studi di Palermo, Palermo, Italy
| | - Tiziana Di Chiara
- Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro"(ProMise), Università degli Studi di Palermo, Palermo, Italy
| | - Giuliana Guggino
- Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro"(ProMise), Università degli Studi di Palermo, Palermo, Italy
- Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", U. O di Reumatologia, Palermo, Italy
| | - Domenico Di Raimondo
- U.O. C di Medicina Interna con Stroke Care, Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", (ProMise), Università degli Studi di Palermo, Piazza delle Cliniche N.2, 90127, Palermo, Italy
- Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro"(ProMise), Università degli Studi di Palermo, Palermo, Italy
| | - Maria Grazia Puleo
- U.O. C di Medicina Interna con Stroke Care, Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", (ProMise), Università degli Studi di Palermo, Piazza delle Cliniche N.2, 90127, Palermo, Italy
- Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro"(ProMise), Università degli Studi di Palermo, Palermo, Italy
| | - Angelo Ferrante
- Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro"(ProMise), Università degli Studi di Palermo, Palermo, Italy
- Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", U. O di Reumatologia, Palermo, Italy
| | - Rosario Scaglione
- Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro"(ProMise), Università degli Studi di Palermo, Palermo, Italy
- Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", U. O di Reumatologia, Palermo, Italy
| | - Antonio Pinto
- U.O. C di Medicina Interna con Stroke Care, Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", (ProMise), Università degli Studi di Palermo, Piazza delle Cliniche N.2, 90127, Palermo, Italy
- Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro"(ProMise), Università degli Studi di Palermo, Palermo, Italy
| | - Antonino Tuttolomondo
- U.O. C di Medicina Interna con Stroke Care, Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro", (ProMise), Università degli Studi di Palermo, Piazza delle Cliniche N.2, 90127, Palermo, Italy.
- Dipartimento Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro"(ProMise), Università degli Studi di Palermo, Palermo, Italy.
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15
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Morton FR, Jani BD, Mair FS, McLoone P, Canning J, Macdonald S, McQueenie R, Siebert S, Nicholl BI. Association between risk, duration and cause of hospitalisations in people with rheumatoid arthritis and multimorbidity in the UK Biobank and Scottish Early Rheumatoid Arthritis (SERA) cohorts: Longitudinal observational study. Semin Arthritis Rheum 2023; 58:152130. [PMID: 36459724 DOI: 10.1016/j.semarthrit.2022.152130] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 10/18/2022] [Accepted: 10/26/2022] [Indexed: 11/18/2022]
Abstract
OBJECTIVES To investigate association between presence of multimorbidity in people with established and early rheumatoid arthritis (RA) and risk, duration and cause of hospitalisations. DESIGN Longitudinal observational study. SETTING UK Biobank, population-based cohort recruited between 2006 and 2010, and the Scottish Early Rheumatoid Arthritis (SERA), inception cohort recruited between 2011 and 2015. Both linked to mortality and hospitalisation data. PARTICIPANTS 4757 UK Biobank participants self-reporting established RA; 825 SERA participants with early RA meeting the 2010 ACR/EULAR classification criteria. Participants stratified by number of long-term conditions (LTCs) in addition to RA (RA only, RA + 1 LTC and RA + ≥ 2 LTCs) and matched to five non-RA controls. MAIN OUTCOME MEASURES Number and duration of hospitalisations and their causes. Incidence rate ratios (IRR) and 95% confidence intervals (CI) calculated using negative binomial regression models. RESULTS Participants with RA + ≥ 2 LTCs experienced higher hospitalisation rates compared to those with RA alone (UK Biobank: IRR 2.10, 95% CI 1.91 to 2.30; SERA: IRR 1.74, 95% CI 1.23 to 2.48). Total duration of hospitalisation in RA + ≥ 2 LTCs was also higher (UK Biobank: IRR 2.48, 95% CI 2.17 to 2.84; SERA: IRR 1.90, 95% CI 1.07 to 3.38) than with RA alone. Rate and total duration of hospitalisations was higher in UK Biobank RA participants than non-RA controls with equivalent number of LTCs. Hospitalisations for respiratory infection were higher in early RA than established RA and were the commonest cause of hospital admission in early RA. CONCLUSIONS Participants with established or early RA with multimorbidity experienced a higher rate and duration of hospitalisations than those with RA alone and with non-RA matched controls.
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Affiliation(s)
- Fraser R Morton
- School of Infection and Immunity, University of Glasgow, Glasgow, UK.
| | - Bhautesh D Jani
- General Practice and Primary Care, School of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Frances S Mair
- General Practice and Primary Care, School of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Philip McLoone
- General Practice and Primary Care, School of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Jordan Canning
- General Practice and Primary Care, School of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Sara Macdonald
- General Practice and Primary Care, School of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Ross McQueenie
- General Practice and Primary Care, School of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Stefan Siebert
- School of Infection and Immunity, University of Glasgow, Glasgow, UK
| | - Barbara I Nicholl
- General Practice and Primary Care, School of Health and Wellbeing, University of Glasgow, Glasgow, UK
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16
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Burisch J. Is hypertension an extra-intestinal manifestation of inflammatory bowel disease? United European Gastroenterol J 2023; 11:7-8. [PMID: 36658105 PMCID: PMC9892475 DOI: 10.1002/ueg2.12359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Affiliation(s)
- Johan Burisch
- Gastrounit, Medical DivisionCopenhagen University Hospital – Amager and HvidovreHvidovreDenmark,Copenhagen Center for Inflammatory Bowel Disease in ChildrenAdolescents and AdultsCopenhagen University Hospital – Amager and HvidovreHvidovreDenmark
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Stakhova AP, Kondratiuk VE, Karmazina OM, Karmazin YO. FEATURES OF THE DAILY PROFILE OF ARTERIAL BLOOD PRESSURE IN PATIENTS WITH RHEUMATOID ARTHRITIS IN COMBINATION WITH ARTERIAL HYPERTENSION. WIADOMOSCI LEKARSKIE (WARSAW, POLAND : 1960) 2023; 76:35-40. [PMID: 36883487 DOI: 10.36740/wlek202301104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
OBJECTIVE The aim: To determine the features of daily shifts in blood pressure (BP), the influence of the presence of rheumatoid arthritis (RA) on BP control and identify factors that affect BP among patients with RA in combination with resistant hypertension (RH). PATIENTS AND METHODS Materials and methods: All material for writing this scientific work were the results of a comprehensive survey of 201 people with RH and RA, hypertension (H) and RA, RA without H, H without RA and relatively healthy individuals. A laboratory study was performed: rheumatoid factor, C-reactive protein (CRP), K+ serum, and creatinine levels. All patients underwent office BP measurement and ambulatory BP monitoring for 24 hours. Statistical processing of the study results was carried out using "IBM SPSS Statistics 22". RESULTS Results: Among patients with RA in combination with RH non-dippers (38.7%) are the most common type of BP profile. Patients with RH in combination with RA are characterized by an increase in BP more at night (p <0.003), which corresponds to the high frequency of night-peackers (17.7%). The presence of RA determines worse control of diastolic BP (p <0.01) and more vascular overload on organs and systems during the night (p <0.05). CONCLUSION Conclusions: An increase in BP in patients with RA in combination with RH is more significant at night, characterized by poorer BP control and greater vascular load at night indicating the need for tighter control of BP during sleep. Non-dippers are most often detected among patients with RA in combination with RH, which is prognostically unfavorable for the development of nocturnal "vascular accidents".
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Zhao J, Xu L, Chang C, Jiang P, Wei K, Shi Y, Xu L, Zheng Y, Shan Y, Bian Y, Li L, Guo S, Schrodi SJ, Wang R, He D. Circulating methylation level of HTR2A is associated with inflammation and disease activity in rheumatoid arthritis. Front Immunol 2022; 13:1054451. [PMID: 36561742 PMCID: PMC9763304 DOI: 10.3389/fimmu.2022.1054451] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 11/23/2022] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES HTR2A is previously identified as a susceptibility gene for rheumatoid arthritis (RA). In this study, we performed the association analysis between DNA methylation of HTR2A with RA within peripheral blood samples. METHODS We enrolled peripheral blood samples from 235 patients with RA, 30 osteoarthritis (OA) patients, and 30 healthy controls. The DNA methylation levels of about 218 bp from chr13: 46898190 to chr13: 46897973 (GRCh38/hg38) around HTR2A cg15692052 from patients were analyzed by targeted methylation sequencing. RESULTS We measured methylation status for 7 CpGs in the promoter region of HTR2A and obseved overall methylation status are signficantly increased in RA compared with normal inviduals (FDR= 9.05 x 10-5). The average cg15692052 methylation levels (methylation score) showed a positive correlation with CRP (r=0.15, P=0.023). Compared with the OA group or HC group, the proportion of haplotypes CCCCCCC (FDR=0.02 and 2.81 x 10-6) is signficantly increased while TTTTTCC (FDR =0.01) and TTTTTTT(FDR =6.92 x 10-3) are significantly decreased in RA. We find methylation haplotypes combining with RF and CCP could signficantly enhance the performance of the diagnosing RA and its comorbidities (hypertension, interstitial lung disease, and osteoporosis), especially in interstitial lung disease. CONCLUSIONS In our study, we found signficant hypermethylation of promoter region of HTR2A which indicates the potential clinical diagnostic role in rheumatoid arthritis.
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Affiliation(s)
- Jianan Zhao
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
| | - Lingxia Xu
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
| | - Cen Chang
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
| | - Ping Jiang
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
| | - Kai Wei
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
| | - Yiming Shi
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
| | - Linshuai Xu
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
| | - Yixin Zheng
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
| | - Yu Shan
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
| | - Yanqin Bian
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- Arthritis Institute of Integrated Traditional and Western medicine, Shanghai Chinese Medicine Research Institute, Shanghai, China
| | - Li Li
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- Arthritis Institute of Integrated Traditional and Western medicine, Shanghai Chinese Medicine Research Institute, Shanghai, China
| | - Shicheng Guo
- Computation and Informatics in Biology and Medicine, University of Wisconsin-Madison, Madison, WI, United States
- Department of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Steven J. Schrodi
- Computation and Informatics in Biology and Medicine, University of Wisconsin-Madison, Madison, WI, United States
- Department of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States
| | - Rongsheng Wang
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
| | - Dongyi He
- Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
- Arthritis Institute of Integrated Traditional and Western medicine, Shanghai Chinese Medicine Research Institute, Shanghai, China
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Rollefstad S, Ikdahl E, Wibetoe G, Sexton J, Crowson CS, van Riel P, Kitas GD, Graham I, Dahlqvist SR, Karpouzas G, Myasoedova E, Gonzalez-Gay MA, Sfikakis PP, Tektonidou MG, Lazarini A, Vassilopoulos D, Kuriya B, Hitchon CA, Stoenoiu MS, Durez P, Pascual-Ramos V, Galarza-Delgado DA, Faggiano P, Misra DP, Borg A, Mu R, Mirrakhimov EM, Gheta D, Myasoedova S, Krougly L, Popkova T, Tuchyňová A, Tomcik M, Vrablik M, Lastuvka J, Horák P, Medková H, Semb AG. An international audit of the management of dyslipidaemia and hypertension in patients with rheumatoid arthritis: results from 19 countries. EUROPEAN HEART JOURNAL. CARDIOVASCULAR PHARMACOTHERAPY 2022; 8:539-548. [PMID: 34232315 DOI: 10.1093/ehjcvp/pvab052] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 05/12/2021] [Accepted: 07/05/2021] [Indexed: 01/05/2023]
Abstract
AIMS To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions and to evaluate the management and goal attainment of lipids and blood pressure (BP). METHODS AND RESULTS The survey of CVD risk factors in patients with RA was conducted in 14 503 patients from 19 countries during 2014-19. The treatment goal for BP was <140/90 mmHg. CVD risk prediction and lipid goals were according to the 2016 European guidelines. Overall, 21% had a very high estimated risk of CVD, ranging from 5% in Mexico, 15% in Asia, 19% in Northern Europe, to 31% in Central and Eastern Europe and 30% in North America. Of the 52% with indication for lipid-lowering treatment (LLT), 44% were using LLT. The lipid goal attainment was 45% and 18% in the high and very high risk groups, respectively. Use of statins in monotherapy was 24%, while 1% used statins in combination with other LLT. Sixty-two per cent had hypertension and approximately half of these patients were at BP goal. The majority of the patients used antihypertensive treatment in monotherapy (24%), while 10% and 5% as a two- or three-drug combination. CONCLUSION We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures.
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Affiliation(s)
- Silvia Rollefstad
- Preventive Cardio-Rheuma Clinic, Division of Rheumatology and Research, Diakonhjemmet Hospital, Diakonveien 12, 0370 Oslo, Norway
| | - Eirik Ikdahl
- Preventive Cardio-Rheuma Clinic, Division of Rheumatology and Research, Diakonhjemmet Hospital, Diakonveien 12, 0370 Oslo, Norway
| | - Grunde Wibetoe
- Preventive Cardio-Rheuma Clinic, Division of Rheumatology and Research, Diakonhjemmet Hospital, Diakonveien 12, 0370 Oslo, Norway
| | - Joe Sexton
- Preventive Cardio-Rheuma Clinic, Division of Rheumatology and Research, Diakonhjemmet Hospital, Diakonveien 12, 0370 Oslo, Norway
| | - Cynthia S Crowson
- Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
- Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | | | - George D Kitas
- Dudley Group NHS Foundation Trust, Dudley, West Midlands, UK
| | | | | | - George Karpouzas
- The Lundquist Institute, Harbor-UCLA Medical Center, Torrance, CA, USA
| | - Elena Myasoedova
- Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | | | - Petros P Sfikakis
- Joint Rheumatology Program, First Department of Propaedeutic Internal Medicine, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria G Tektonidou
- Joint Rheumatology Program, First Department of Propaedeutic Internal Medicine, Laiko Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Argyro Lazarini
- Joint Rheumatology Program, 2nd Department of Medicine and Laboratory, Hippokration General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Vassilopoulos
- Joint Rheumatology Program, 2nd Department of Medicine and Laboratory, Hippokration General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Bindee Kuriya
- Department of Medicine, Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada
| | - Carol A Hitchon
- Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Maria Simona Stoenoiu
- Rheumatology Department, Cliniques Universitaires Saint Luc, Institut de recherche expérimentale et clinique, Université catholique de Louvain, Brussels, Belgium
| | - Patrick Durez
- Rheumatology Department, Cliniques Universitaires Saint Luc, Institut de recherche expérimentale et clinique, Université catholique de Louvain, Brussels, Belgium
| | - Virginia Pascual-Ramos
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México
| | | | | | - Durga Prasanna Misra
- Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India
| | | | - Rong Mu
- Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing 100044, China
| | | | - Diane Gheta
- Tallagh University Hospital, Dublin, Ireland
| | | | - Lev Krougly
- Center of Cardiology of Russian Ministry of Healthcare, Moscow, Russia
| | - Tatiana Popkova
- V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia
| | - Alena Tuchyňová
- National Institute of Rheumatic Diseases, 92101 Piešťany, Slovensko, Slovakia
| | - Michal Tomcik
- Institute of Rheumatology, Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Michal Vrablik
- Third Department of Internal Medicine, Department of Endocrinology and Metabolism, First Medical Faculty, Charles University and General Faculty Hospital, Prague, Czech Republic
| | - Jiri Lastuvka
- Third Department of Internal Medicine, Department of Endocrinology and Metabolism, First Medical Faculty, Charles University and General Faculty Hospital, Prague, Czech Republic
- First Medical Faculty, Charles University, Prague, Czech Republic
| | - Pavel Horák
- Iii Interna klinika fn Olomouc, Olomouc, Czech Republic
| | - Helena Medková
- Division of Rheumatology, 2nd Department of Internal Medicine-Gastroenterology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Hradec Králové, Czech Republic
| | - Anne Grete Semb
- Preventive Cardio-Rheuma Clinic, Division of Rheumatology and Research, Diakonhjemmet Hospital, Diakonveien 12, 0370 Oslo, Norway
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20
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Al-Ahmari AK. Prevalence of Hypertension and Its Associated Risk Factors Among Patients with Rheumatoid Arthritis in the Kingdom of Saudi Arabia. Int J Gen Med 2022; 15:6507-6517. [PMID: 35966507 PMCID: PMC9374201 DOI: 10.2147/ijgm.s370956] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Accepted: 08/04/2022] [Indexed: 11/26/2022] Open
Abstract
Purpose Data regarding hypertension prevalence among patients with rheumatoid arthritis in Saudi Arabia are scarce. This study was aimed at estimating the prevalence of hypertension and its associated risk factors among patients with rheumatoid arthritis in Saudi Arabia. Patients and Methods This was a cross-sectional study of adult patients with rheumatoid arthritis who presented at the OPD of two major hospitals in Riyadh city. Patient information such as demographic characteristics, comorbidities, drug use, and other clinical data were captured through medical record review and supplemented by patient interviews. Multivariate logistic regression was used to identify the significant factors for hypertension. Results The prevalence of hypertension was found in 32.35% of the 1490 rheumatoid arthritis patients who participated in our study. Logistic regression analyses revealed that advanced age, female sex, low education level, unemployment, smoking, and consulting with physicians less than two times within the past 12 months were risk factors for increased hypertension prevalence among patients with rheumatoid arthritis. A significantly higher risk of hypertension was observed among RA patients with obesity, diabetes, hyperlipidemia, cancer, kidney disease, osteoporosis, and Parkinson’s disease than among patients without these comorbidities. Conclusion Hypertension is highly prevalent among patients with rheumatoid arthritis, and advanced age, sex, low educational level, unemployment, smoking, and comorbidities are risk factors for increased hypertension prevalence.
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Affiliation(s)
- Abdullah K Al-Ahmari
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Riyadh, Saudi Arabia
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21
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Abstract
PURPOSE OF REVIEW The purpose of our review was to evaluate current standards in clinical practice in determining overall cardiac risk in female patients with chronic rheumatologic diseases. We hoped to not only summarize known cardiac manifestations of various chronic rheumatologic diseases but also determine the effectiveness of new risk scores in determining cardiac risk in this patient population. RECENT FINDINGS Chronic rheumatologic diseases have been associated with various cardiac manifestations for some time, with initial studies involving risk of coronary artery disease (CAD) in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, recent studies have shown numerous other cardiac manifestations associated with these and other chronic rheumatologic diseases. Risk scores have been used for several decades to help determine overall cardiac risk in the general population, but these risk scores have notoriously underestimated the risk of cardiac disease in woman and in patients with chronic rheumatologic diseases. These diseases, often with a female predominance, can impact long-term mortality and have devastating consequences if not monitored and treated appropriately. Thus, new risk scores have been developed over the last several years to help improve detection and awareness of cardiac disease in these patients. Novel modified risk scores have found some success at improving the detection of cardiac disease in patients with chronic rheumatologic diseases. Further studies looking at these risk scores need to determine the accuracy of these scores and where they fall short. With the advent of advanced imaging technologies, future risk scores may involve certain imaging-based markers to help guide accurate risk determination.
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Affiliation(s)
- Tyler Schmidt
- Department of Cardiovascular Medicine, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA
| | - Rekha Mankad
- Department of Cardiovascular Medicine, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA.
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22
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Santos JD, Oliveira Neto JT, Barros PR, Damasceno LEA, Lautherbach N, Assis AP, Silva CAA, Sorgi CA, Faccioli LH, Kettelhut IC, Salgado HC, Carneiro FS, Alves Filho JC, Tostes RC. Th17 cells-linked mechanisms mediate vascular dysfunction induced by testosterone in a mouse model of gender-affirming hormone therapy. Am J Physiol Heart Circ Physiol 2022; 323:H322-H335. [PMID: 35714175 DOI: 10.1152/ajpheart.00182.2022] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Clinical data point to adverse cardiovascular events elicited by testosterone replacement therapy. Testosterone is the main hormone used in gender-affirming hormone therapy (GAHT) by transmasculine people. However, the cardiovascular impact of testosterone in experimental models of GAHT remains unknown. Sex hormones modulate T cells activation, and immune mechanisms contribute to cardiovascular risk. The present study evaluated whether testosterone negatively impacts female cardiovascular function by enhancing Th17 cells-linked effector mechanisms. Female (8 weeks-old) C57BL/6J mice received testosterone (48 mg.Kg-1.week-1) for 8 weeks. Male mice were used for phenotypical comparisons. The hormone-treatment in female mice increased circulating testosterone to levels observed in male mice. Testosterone increased lean body mass and body mass index, and decreased perigonadal fat mass, mimicking clinical findings. After 8 weeks, testosterone decreased endothelium-dependent vasodilation and increased circulating Th17 cells. After 24 weeks, testosterone increased blood pressure in female mice. Ovariectomy did not intensify phenotypical or cardiovascular effects by testosterone. Female mice lacking T and B cells [Rag1 knockout (-/-)], as well as female mice lacking IL-17 receptor (IL-17Ra-/-), did not exhibit vascular dysfunction induced by testosterone. Testosterone impaired endothelium-dependent vasodilation in female mice lacking γδ T cells, similarly to the observed in wild type female mice. Adoptive transfer of CD4+ T cells restored testosterone-induced vascular dysfunction in Rag1-/- female mice. Together, these data suggest that CD4+ T cells, most likely Th17 cells, are central to vascular dysfunction induced by testosterone in female mice, indicating that changes in immune cells balance are important in the GAHT in transmasculine people.
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Affiliation(s)
- Jeimison D Santos
- Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
| | - José T Oliveira Neto
- Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
| | - Paula R Barros
- Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
| | - Luis Eduardo Alves Damasceno
- Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
| | - Natalia Lautherbach
- Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil
| | - Ana P Assis
- Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil
| | - Carlos A A Silva
- Department of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil
| | - Carlos A Sorgi
- Department of Chemistry, Faculty of Philosophy, Sciences and Letters at Ribeira Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
| | - Lucia H Faccioli
- Department of Clinical Analyses, Toxicology and Food Science, Faculty of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
| | - Isis C Kettelhut
- Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, Brazil
| | - Helio C Salgado
- Department of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil
| | - Fernando S Carneiro
- Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
| | - Jose C Alves Filho
- Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
| | - Rita C Tostes
- Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
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Chaudhari S, Pham GS, Brooks CD, Dinh VQ, Young-Stubbs CM, Shimoura CG, Mathis KW. Should Renal Inflammation Be Targeted While Treating Hypertension? Front Physiol 2022; 13:886779. [PMID: 35770194 PMCID: PMC9236225 DOI: 10.3389/fphys.2022.886779] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 05/17/2022] [Indexed: 11/28/2022] Open
Abstract
Despite extensive research and a plethora of therapeutic options, hypertension continues to be a global burden. Understanding of the pathological roles of known and underexplored cellular and molecular pathways in the development and maintenance of hypertension is critical to advance the field. Immune system overactivation and inflammation in the kidneys are proposed alternative mechanisms of hypertension, and resistant hypertension. Consideration of the pathophysiology of hypertension in chronic inflammatory conditions such as autoimmune diseases, in which patients present with autoimmune-mediated kidney inflammation as well as hypertension, may reveal possible contributors and novel therapeutic targets. In this review, we 1) summarize current therapies used to control blood pressure and their known effects on inflammation; 2) provide evidence on the need to target renal inflammation, specifically, and especially when first-line and combinatory treatment efforts fail; and 3) discuss the efficacy of therapies used to treat autoimmune diseases with a hypertension/renal component. We aim to elucidate the potential of targeting renal inflammation in certain subsets of patients resistant to current therapies.
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Affiliation(s)
| | | | | | | | | | | | - Keisa W. Mathis
- Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX, United States
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Ahmed O, Krishnamurthy V, Kaba RA, Tahir H. The Management of Cardiovascular Disease Risk in Patients with Rheumatoid Arthritis. Expert Opin Pharmacother 2022; 23:947-958. [PMID: 35575484 DOI: 10.1080/14656566.2022.2076594] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Rheumatoid Arthritis (RA) is a chronic inflammatory disorder associated with an increased incidence and prevalence of cardiovascular disease (CVD), including myocardial infarction and heart failure. In addition to traditional risk factors, evidence suggests inflammation is critical to the pathophysiology of both conditions. Despite the association being well-recognised, challenges remain in managing cardiovascular risk in RA. AREAS COVERED This manuscript analyses the association between CVD and RA andexplores the limitations in evaluating cardiovascular risk in RA with available risk assessment tools. The authors review and discuss the optimal management of traditional risk factors such as hypertension and dyslipidaemia and contemporary risk factors such as inflammation and analyse the cardiovascular impact of RA medications. EXPERT OPINION Analysis points to the critical role of inflammation in the pathogenesis of RA and CVD. It is well established that conventional disease-modifying anti-rheumatic drugs (DMARDs) improve cardiovascular outcomes; however, underlying risk often remains underappreciated. The authors suggest there remains an opportunity to improve mortality and morbidity with the early recognition and identification of at-risk populations and the timely initiation of appropriate cardiovascular and anti-inflammatory medications. More research is necessary into the role that imaging may play in stratifying risk and in the longer-term cardiovascular impact of biological DMARDs.
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Affiliation(s)
- Omar Ahmed
- Senior Research Fellow in Cardiology & Cardiac Electrophysiology, St George's University Hospitals NHS Foundation Trust, Blackshaw Road, London, London, UK
| | - Vinodh Krishnamurthy
- Research Practitioner, Royal Free London NHS Trust, Barnet Hospital, Wellhouse Lane, Wellhouse Lane EN5 3DJ, UK
| | - Riyaz A Kaba
- Consultant in Cardiac Electrophysiology & Devices, St George's University Hospitals NHS Foundation Trust, Blackshaw Road, London, UK
| | - Hasan Tahir
- Consultant Physician & Rheumatologist, Honorary Clinical Professor, University College London, Royal Free London NHS Trust, Wellhouse Lane EN5 3DJ, UK
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25
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Hill J, Harrison J, Christian D, Reed J, Clegg A, Duffield SJ, Goodson N, Marson T. The prevalence of comorbidity in rheumatoid arthritis: a systematic review and meta-analysis. Br J Community Nurs 2022; 27:232-241. [PMID: 35522453 DOI: 10.12968/bjcn.2022.27.5.232] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
This systematic review and meta-analysis estimates the prevalence of common comorbid health disorders in adults with rheumatoid arthritis (RA). A multi-database search strategy was undertaken. Screening, data extraction and quality assessment were carried out by two independent reviewers. A meta-analysis and meta-regression were used to generate a pooled prevalence estimate and identify relevant moderators. After study selection, 33 studies (74633 participants) were included in the meta-analysis. Some 31 studies were judged to be of low risk of bias, and two studies were judged to be at moderate risk of bias. The three most common comorbidities in RA were anxiety disorders (62.1%, 95% Cl: 43.6%; 80.6%), hypertension (37.7%, 95% Cl: 29.2%; 46.2%) and depression (32.1%, 95% Cl: 21.6%; 42.7%). There was substantial statistically significant heterogeneity for all comorbidities (I2 ≥77%). Meta-regression identified that the covariate of mean age (unit increase) had a statistically significant effect on the prevalence of hypertension (+2.3%, 95% Cl: 0.4%; 4.2%), depression (-0.5%, 95% Cl: -0.6%; -0.4%) and cancer (0.5%, 95% Cl: 0.2%; 0.8%) in adults with RA. A country's income was identified to have a statistically significant effect on the prevalence of depression, with low-to moderate-income countries having 40% (95% Cl: 14.0%; 66.6%) higher prevalence than high-income countries. No studies consider health inequalities. It is concluded that comorbidities are prevalent among people with RA, particularly those associated with mental health and circulatory conditions. Provision of health services should reflect the importance of such multimorbidity and the consequences for quality and length of life.
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Affiliation(s)
- James Hill
- Senior Research Fellow in Evidence Synthesis, Synthesis, Economic Evaluation and Decision Science (SEEDS) Group, University of Central Lancashire
| | - Joanna Harrison
- Research Fellow in Evidence Synthesis & Summary, Synthesis, Economic Evaluation and Decision Science (SEEDS) Group, University of Central Lancashire
| | - Danielle Christian
- Research Associate, Stroke Research Team, University of Central Lancashire
| | - Janet Reed
- Library Customer Services Manager, Heriot-Watt University, Edinburgh
| | - Andrew Clegg
- Professor of Health Services Research, Synthesis, Economic Evaluation and Decision Science (SEEDS) Group, University of Central Lancashire
| | - Stephen J Duffield
- Senior Analyst - Methods and Standards, National Institute for Health and Care Excellence, Manchester
| | - Nicola Goodson
- Consultant Rheumatologist and Senior Lecturer, University Hospital Aintree, Liverpool
| | - Tony Marson
- Professor of Neurology, University of Liverpool
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26
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Ferguson LD, Sattar N, McInnes IB. Managing Cardiovascular Risk in Patients with Rheumatic Disease. Rheum Dis Clin North Am 2022; 48:429-444. [PMID: 35400369 DOI: 10.1016/j.rdc.2022.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Individuals with rheumatoid arthritis, systemic lupus erythematosus, or gout have increased risk of cardiovascular disease (CVD) compared with the general population. This risk relates to a combination of traditional cardiovascular risk factors and disease-specific factors. Screening for CVD is important because CVD contributes to significant morbidity and mortality. Management includes tight control of disease activity to reduce inflammation, but with care to minimize use of nonsteroidal anti-inflammatory drugs and prolonged courses of high-dose corticosteroids. Traditional cardiovascular risk factors should be managed with a combination of lifestyle interventions and pharmacotherapy. The decision to start antihypertensive and lipid-lowering therapy should be based on individual CVD risk.
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Affiliation(s)
- Lyn D Ferguson
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
| | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
| | - Iain B McInnes
- Institute of Infection, Immunity and Inflammation, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
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27
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Almalki ZS, AlOmari BA, Alshammari T, Alshlowi A, Khan MF, Hazazi A, Alruwaily M, Alsubaie S, Alanazi F, Aldossary N, Albahkali R. Uncontrolled blood pressure among hypertensive adults with rheumatoid arthritis in Saudi Arabia: A cross-sectional study. Medicine (Baltimore) 2022; 101:e28763. [PMID: 35089255 PMCID: PMC8797535 DOI: 10.1097/md.0000000000028763] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Revised: 11/04/2021] [Accepted: 01/15/2022] [Indexed: 01/05/2023] Open
Abstract
ABSTRACT Despite the availability and advancement of diagnostic and treatments with demonstrated benefits in minimizing cardiovascular morbidity and mortality, hypertension control rates remain suboptimal. Therefore, this research aimed to determine the prevalence of uncontrolled BP in rheumatoid arthritis (RA) patients and understand all potential risk factors for uncontrolled BP.We conducted a cross-sectional study on RA patients in 2 rheumatology clinics in 2 public hospitals in Riyadh. Patients' information such as demographics, comorbidities, drug use, and other clinical data were captured through a review of medical records and supplemented by patient interviews. Multivariate logistic regression was utilized for the analysis to identify the significant factors of uncontrolled BP (systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg).In total, 834 subjects with RA and concomitant BP were involved in this cross-sectional study. The prevalence of uncontrolled BP was found to be 31.65% among all the study population. Multivariate analysis showed that males, subjects above 60 years of age, and smokers had a distinctly higher occurrence of uncontrolled BP. Among the patients with comorbid conditions, those with obesity, hyperlipidemia, diabetes, anemia, cancer, and reflex or gastroesophageal reflux disease also showed a significantly higher risk of uncontrolled BP (P < .05).The rate of uncontrolled BP was found to be alarmingly high in the study population. Age, gender, smoking, diabetes, obesity, hyperlipidemia, cancer, gastroesophageal reflux disease, and osteoporosis are independently linked with lack of BP control.
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Affiliation(s)
- Ziyad S. Almalki
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Riyadh, Saudi Arabia
| | - Bedor Abdullah AlOmari
- Internal Medicine and Rheumatology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | | | - Areej Alshlowi
- Clinical Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia
| | - Mohd Faiyaz Khan
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Riyadh, Saudi Arabia
| | - Ali Hazazi
- College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Riyadh, Saudi Arabia
| | - Maha Alruwaily
- Clinical Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia
| | - Sarah Alsubaie
- Clinical Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia
| | - Faten Alanazi
- Clinical Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia
| | - Norah Aldossary
- Clinical Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia
| | - Raseel Albahkali
- Clinical Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia
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28
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Dimitroulas T, Anyfanti P, Bekiari E, Angeloudi E, Pagkopoulou E, Kitas G. Arterial stiffness in rheumatoid arthritis: Current knowledge and future perspectivess. INDIAN JOURNAL OF RHEUMATOLOGY 2022. [DOI: 10.4103/injr.injr_254_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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29
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Agca R, Smulders Y, Nurmohamed M. Cardiovascular disease risk in immune-mediated inflammatory diseases: recommendations for clinical practice. Heart 2022; 108:73-79. [PMID: 33674356 PMCID: PMC8666803 DOI: 10.1136/heartjnl-2019-316378] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Affiliation(s)
- Rabia Agca
- Rheumatology, Amsterdam UMC and Reade, Amsterdam, Noord-Holland, The Netherlands
| | - Yvo Smulders
- Internal Medicine, Amsterdam UMC, Amsterdam, Noord-Holland, The Netherlands
| | - Michael Nurmohamed
- Rheumatology, Amsterdam UMC and Reade, Amsterdam, Noord-Holland, The Netherlands
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30
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Perrotta M, Carnevale D. Brain Areas Involved in Modulating the Immune Response Participating in Hypertension and Its Target Organ Damage. Antioxid Redox Signal 2021; 35:1515-1530. [PMID: 34269604 DOI: 10.1089/ars.2021.0142] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Significance: Hypertension is a multifactorial disease ensuing from the continuous challenge imposed by several risk factors on the cardiovascular system. Classically known pathophysiological alterations associated with hypertension comprise neurogenic mechanisms dysregulating the autonomic nervous system (ANS), vascular dysfunction, and excessive activation of the renin angiotensin system. During the past few years, a considerable number of studies indicated that immune activation and inflammation also have an important role in the onset and maintenance of hypertension. Critical Issues: On these premises, it has been necessary to reconsider the pathophysiological mechanisms underlying hypertension development, taking into account the potential interactions established between classically known determinants of high blood pressure and the immune system. Recent Advances: Interestingly, central nervous system areas controlling cardiovascular functions are enriched with Angiotensin II receptors. Observations showing that these brain areas are crucial for mediating peripheral ANS and immune responses were suggestive of a critical role of neuroimmune interactions in hypertension. In fact, the ANS, characterized by an intricate network of afferent and efferent fibers, represents an intermediate between the brain and peripheral responses that are essential for blood pressure regulation. Future Directions: In this review, we will summarize studies showing how specific brain areas can modulate immune responses that are involved in hypertension. Antioxid. Redox Signal. 35, 1515-1530.
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Affiliation(s)
- Marialuisa Perrotta
- Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Daniela Carnevale
- Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy.,Research Unit of Neuro and Cardiovascular Pathophysiology, IRCCS Neuromed, Pozzilli, Italy
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Liew JW, Cannon CA, Ji Y, Littman AJ, Hawes SE. Association of Arthritis and Antihypertensive Medication Use Among Individuals With Hypertension: A Cross-Sectional Analysis of the 2017 Behavioral Risk Factor Surveillance System. J Clin Rheumatol 2021; 27:e357-e361. [PMID: 32541614 PMCID: PMC7736264 DOI: 10.1097/rhu.0000000000001426] [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] [Indexed: 11/26/2022]
Abstract
BACKGROUND The aim of this study was to assess whether arthritis is associated with lower antihypertensive medication (AHM) use among those with hypertension and whether this relationship differs by age or cardiovascular (CV) comorbidity. METHODS The data were from the 2017 Behavioral Risk Factor Surveillance System. We employed survey weights to account for the complex sampling design and nonresponse bias. We used generalized linear models to estimate unadjusted and adjusted prevalence ratios (PRs) and 95% confidence intervals comparing AHM use among those with severe or mild arthritis to those without arthritis, stratified by age, sex, and CV comorbidity. RESULTS Among 173,098 adults with hypertension, 26.0% had severe arthritis and 22.3% had mild arthritis. Compared with those without arthritis, individuals with mild or severe arthritis were older, predominantly female, with lower income and more comorbidities. After adjustment for sex, race, inability to afford medications, and CV comorbidity, the prevalence ratios for AHM use were stronger for younger versus older age groups. Associations did not differ significantly by sex or CV comorbidity. Associations were similar for mild and severe arthritis, compared with no arthritis. CONCLUSIONS Among individuals with hypertension, those with arthritis had significantly higher prevalences of AHM use compared with those without arthritis. Higher prevalences of AHM use were seen with older age categories, although a stronger association of arthritis and AHM use was found in younger age groups. Future studies on hypertension management in arthritis should examine these relationships more closely.
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32
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Bartoloni E, Angeli F, Marcucci E, Perricone C, Cafaro G, Riccini C, Spighi L, Gildoni B, Cavallini C, Verdecchia P, Gerli R. Unattended compared to traditional blood pressure measurement in patients with rheumatoid arthritis: a randomised cross-over study. Ann Med 2021; 53:2050-2059. [PMID: 34751628 PMCID: PMC8583925 DOI: 10.1080/07853890.2021.1999493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Accepted: 10/25/2021] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Hypertension is characterised by a high prevalence, low awareness and poor control among rheumatoid arthritis (RA) patients. Correct blood pressure (BP) measurement is highly important in these subjects. The "unattended" BP measurement aims to reduce the "white-coat effect," a phenomenon associated with cardiovascular risk. Data on "unattended" BP measurement in RA and its impact on hypertensive organ damage are very limited. METHODS BP was measured in the same patient both traditionally ("attended" BP) and by the "unattended" protocol (3 automated office BP measurements, at 1-min intervals, after 5 min of rest, with patient left alone) by a randomised cross-over design. Patients underwent clinical examination, 12-lead electrocardiography and trans-thoracic echocardiography to evaluate cardiac damage. RESULTS Sixty-two RA patients (mean age 67 ± 9 years, 87% women) were enrolled. Hypertension was diagnosed in 79% and 66% of patients according to ACC/AHA and ESC/ESH criteria, respectively. Concordance correlation coefficients between the two techniques were 0.55 (95%, CI 0.38-0.68) for systolic BP and 0.73 (95%, CI 0.60-0.82) for diastolic BP. "Unattended" (121.7/68.6 mmHg) was lower than "attended" BP (130.5/72.8 mmHg) for systolic and diastolic BP (both p < .0001). Among the two techniques, only "unattended" systolic BP showed a significant association with left ventricular mass (r = 0.11; p = .40 for "attended" BP; r = 0.27; p = .036 for unattended BP; difference between slopes: z = 3.92; p = .0001). CONCLUSIONS In RA patients, "unattended" BP is lower than traditional ("attended") BP and more closely associated with LV mass. In these patients, the "unattended" automated BP measurement is a promising tool which requires further evaluation.KEY MESSAGES"Unattended" automated blood pressure registration, aimed to reduce the "white-coat effect" is lower than "attended" value in rheumatoid arthritis patients."Unattended" blood pressure is more closely associated with left ventricular mass than "attende" registration.
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Affiliation(s)
- Elena Bartoloni
- Rheumatology Unit, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Fabio Angeli
- Department of Medicine and Surgery, University of Insubria and Department of Medicine and Cardiopulmonary Rehabilitation, Maugeri Care and Research Institutes, IRCCS Tradate, Varese, Italy
| | - Elisa Marcucci
- Rheumatology Unit, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Carlo Perricone
- Rheumatology Unit, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Giacomo Cafaro
- Rheumatology Unit, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Clara Riccini
- Department of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy
| | - Lorenzo Spighi
- Department of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy
| | - Benedetta Gildoni
- Rheumatology Unit, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Claudio Cavallini
- Department of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy
| | - Paolo Verdecchia
- Department of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy
- Fondazione Umbra Cuore e Ipertensione, Perugia, Italy
| | - Roberto Gerli
- Rheumatology Unit, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
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Huang YJ, Chen JS, Luo SF, Kuo CF. Comparison of Indexes to Measure Comorbidity Burden and Predict All-Cause Mortality in Rheumatoid Arthritis. J Clin Med 2021; 10:jcm10225460. [PMID: 34830741 PMCID: PMC8618526 DOI: 10.3390/jcm10225460] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 11/04/2021] [Accepted: 11/11/2021] [Indexed: 11/20/2022] Open
Abstract
Objectives: To examine the comorbidity burden in patients with rheumatoid arthritis (RA) patients using a nationwide population-based cohort by assessing the Charlson Comorbidity Index (CCI), Elixhauser Comorbidity Index (ECI), Multimorbidity Index (MMI), and Rheumatic Disease Comorbidity Index (RDCI) scores and to investigate their predictive ability for all-cause mortality. Methods: We identified 24,767 RA patients diagnosed from 1998 to 2008 in Taiwan and followed up until 31 December 2013. The incidence of comorbidities was estimated in three periods (before, during, and after the diagnostic period). The incidence rate ratios were calculated by comparing during vs. before and after vs. before the diagnostic period. One- and 5-year mortality rates were calculated and discriminated by low and high-score groups and modified models for each index. Results: The mean score at diagnosis was 0.8 in CCI, 2.8 in ECI, 0.7 in MMI, and 1.3 in RDCI, and annual percentage changes are 11.0%, 11.3%, 9.7%, and 6.8%, respectively. The incidence of any increase in the comorbidity index was significantly higher in the periods of “during” and “after” the RA diagnosis (incidence rate ratios for different indexes: 1.33–2.77). The mortality rate significantly differed between the high and low-score groups measured by each index (adjusted hazard ratios: 2.5–4.3 for different indexes). CCI was slightly better in the prediction of 1- and 5-year mortality rates. Conclusions: Comorbidities are common before and after RA diagnosis, and the rate of accumulation accelerates after RA diagnosis. All four comorbidity indexes are useful to measure the temporal changes and to predict mortality.
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34
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Argnani L, Zanetti A, Carrara G, Silvagni E, Guerrini G, Zambon A, Scirè CA. Rheumatoid Arthritis and Cardiovascular Risk: Retrospective Matched-Cohort Analysis Based on the RECORD Study of the Italian Society for Rheumatology. Front Med (Lausanne) 2021; 8:745601. [PMID: 34676228 PMCID: PMC8523847 DOI: 10.3389/fmed.2021.745601] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 09/06/2021] [Indexed: 12/28/2022] Open
Abstract
Background: Rheumatoid arthritis (RA) is associated with an increase in cardiovascular (CV) risk. This issue maybe not only explained by a genetic component, as well as by the traditional CV risk factors, but also by an underestimation and undertreatment of concomitant CV comorbidities. Method: This was a retrospective matched-cohort analysis in the Italian RA real-world population based on the healthcare-administrative databases to assess the CV risk factors and incidence of CV events in comparison with the general population. Persistence and adherence to the CV therapy were also evaluated in both groups. Results: In a RA cohort (N = 21,201), there was a greater prevalence of hypertension and diabetes with respect to the non-RA subjects (N = 249,156) (36.9 vs. 33.4% and 10.2 vs. 9.6%, respectively), while dyslipidemia was more frequent in the non-RA group (15.4 vs. 16.5%). Compared with a non-RA cohort, the patients with RA had a higher incidence of atrial fibrillation (incidence rate ratio, IRR 1.28), heart failure (IRR 1.53), stroke (IRR 1.19), and myocardial infarction (IRR 1.48). The patients with RA presented a significantly lower persistence rate to glucose-lowering and lipid-lowering therapies than the controls (odds ratio, OR 0.73 [95% CI 0.6–0.8] and OR 0.82 [0.8–0.9], respectively). The difference in the adherence to glucose-lowering therapy was significant (OR 0.7 [0.6–0.8]), conversely no statistically significant differences emerged regarding the adherence to lipid-lowering therapy (OR 0.89 [95% CI 0.8–1.0]) and anti-hypertensive therapy (OR 0.96 [95% CI 0.9–1.0]). Conclusion: The patients with RA have a higher risk of developing CV events compared with the general population, partially explained by the excess and undertreatment of CV risk factors.
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Affiliation(s)
- Lisa Argnani
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
| | - Anna Zanetti
- Epidemiology Unit, Italian Society for Rheumatology, Milan, Italy.,Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy
| | - Greta Carrara
- Epidemiology Unit, Italian Society for Rheumatology, Milan, Italy
| | - Ettore Silvagni
- Rheumatology Unit, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliero-Universitaria S.Anna, Cona, Italy
| | - Giulio Guerrini
- Biomedical and Biotechnological Science at Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.,Internal Medicine, State Hospital, Borgo Maggiore, San Marino
| | - Antonella Zambon
- Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy
| | - Carlo Alberto Scirè
- Epidemiology Unit, Italian Society for Rheumatology, Milan, Italy.,School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
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35
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El Jamaly H, Eslick GD, Weltman M. Systematic review with meta-analysis: autoimmune hepatitis in pregnancy. Scand J Gastroenterol 2021; 56:1194-1204. [PMID: 34396871 DOI: 10.1080/00365521.2021.1953127] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 06/22/2021] [Accepted: 07/02/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Maternal and fetal outcomes in pregnant patients with autoimmune hepatitis (AIH) has been largely unexplored. AIM This meta-analysis aims to determine the level of evidence associated with both maternal and fetal outcomes in patients with AIH. METHODS We conducted a comprehensive literature search. The studies included AIH patients who had at least one pregnancy with a previously known or index presentation diagnosis of AIH. We used a random-effects model using odds ratios (OR) with 95% confidence intervals (CI). RESULTS Fourteen studies with 1452 AIH patients and with a total of 1556 gestations were included. Analysis revealed statistically significant increased likelihood of diabetes mellitus in the AIH group (OR: 5.73, 95% CI: 2.73-12.02; p < .001, n = 2) compared to controls. Fetal outcomes that indicated a statistically significant association with AIH included premature birth (OR: 2.20, 95% CI:1.66-2.91; p < .001, n = 3), small for gestational age (SGA) births (OR: 2.48, 95% CI:1.37-4.51; p = .003, n = 2) and low birth weight (LBW) (OR: 3.04, 95% CI:1.85-5.01; p < .001, n = 1). AIH pregnancies were significantly less likely to have a full-term birth (OR: 0.32, 95% CI:0.21-0.49; p < .001, n = 2). CONCLUSIONS This meta-analysis provides the first pooled evidence that autoimmune hepatitis is associated with a substantial increase in maternal Pre-pregnancy and gestational diabetes mellitus, and that AIH females are more likely to have premature births, small for gestational age (SGA) births, and low birth weight (LBW) babies and a substantial decrease in full term birth compared to normal controls. This data is important for clinicians managing these patients before, during and after pregnancy.
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Affiliation(s)
- Hydar El Jamaly
- Department of Gastroenterology and Hepatology, Nepean Hospital, Penrith, Australia
- Nepean Clinical School, The University of Sydney, Penrith, Australia
| | - Guy D Eslick
- NHMRC Centre for Digestive Health, Hunter Medical Research Institute, The University of Newcastle, Newcastle, Australia
| | - Martin Weltman
- Department of Gastroenterology and Hepatology, Nepean Hospital, Penrith, Australia
- Nepean Clinical School, The University of Sydney, Penrith, Australia
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Autoimmune Rheumatic Diseases and Vascular Function: The Concept of Autoimmune Atherosclerosis. J Clin Med 2021; 10:jcm10194427. [PMID: 34640445 PMCID: PMC8509415 DOI: 10.3390/jcm10194427] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 09/20/2021] [Accepted: 09/22/2021] [Indexed: 12/18/2022] Open
Abstract
Autoimmune rheumatic diseases (AIRDs) with unknown etiology are increasing in incidence and prevalence. Up to 5% of the population is affected. AIRDs include rheumatoid arthritis, system lupus erythematosus, systemic sclerosis, and Sjögren's syndrome. In patients with autoimmune diseases, the immune system attacks structures of its own body, leading to widespread tissue and organ damage, which, in turn, is associated with increased morbidity and mortality. One third of the mortality associated with autoimmune diseases is due to cardiovascular diseases. Atherosclerosis is considered the main underlying cause of cardiovascular diseases. Currently, because of finding macrophages and lymphocytes at the atheroma, atherosclerosis is considered a chronic immune-inflammatory disease. In active inflammation, the liberation of inflammatory mediators such as tumor necrotic factor alpha (TNFa), interleukine-6 (IL-6), IL-1 and other factors like T and B cells, play a major role in the atheroma formation. In addition, antioxidized, low-density lipoprotein (LDL) antibodies, antinuclear antibodies (ANA), and rheumatoid factor (RF) are higher in the atherosclerotic patients. Traditional risk factors like gender, age, hypercholesterolemia, smoking, diabetes mellitus, and hypertension, however, do not alone explain the risk of atherosclerosis present in autoimmune diseases. This review examines the role of chronic inflammation in the etiology-and progression-of atherosclerosis in autoimmune rheumatic diseases. In addition, discussed here in detail are the possible effects of autoimmune rheumatic diseases that can affect vascular function. We present here the current findings from studies that assessed vascular function changes using state-of-the-art techniques and innovative endothelial function biomarkers.
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A Pilot Study: Hypertension, Endothelial Dysfunction and Retinal Microvasculature in Rheumatic Autoimmune Diseases. J Clin Med 2021; 10:jcm10184067. [PMID: 34575178 PMCID: PMC8467719 DOI: 10.3390/jcm10184067] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Revised: 08/26/2021] [Accepted: 09/07/2021] [Indexed: 12/14/2022] Open
Abstract
Background: The etiology of autoimmune rheumatic diseases is unknown. Endothelial dysfunction and premature atherosclerosis are commonly seen in these patients. Atherosclerosis is considered one of the main causes of cardiovascular diseases. Hypertension is considered the most important traditional cardiovascular risk. This case-control study aimed to investigate the relationship between autoimmune diseases and cardiovascular risk. Methods: This study was carried out in patients with rheumatoid arthritis, RA (n = 10), primary Sjögren syndrome, PSS (n = 10), and healthy controls (n = 10). Mean blood pressure (MBP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse wave velocity (PWV, an indicator of arterial stiffness) were assessed via a Vicorder device. Asymmetric dimethylarginine (ADMA) was measured via ELISA. Retinal photos were taken via a CR-2 retinal camera, and retinal microvasculature analysis was carried out. T-tests were conducted to compare the disease and control groups. ANOVA and ANOVA—ANCOVA were also used for the correction of covariates. Results: A high prevalence of hypertension was seen in RA (80% of cases) and PSS (40% of cases) compared to controls (only 20% of cases). Significant changes were seen in MBP (RA 101 ± 11 mmHg; PSS 93 ± 10 mm Hg vs. controls 88 ± 7 mmHg, p = 0.010), SBP (148 ± 16 mmHg in RA vs. 135 ± 16 mmHg in PSS vs. 128 ± 11 mmHg in control group; p = 0.007), DBP (77 ± 8 mmHg in RA, 72 ± 8 mmHg in PSS vs. 67 ± 6 mmHg in control; p = 0.010 in RA compared to the controls). Patients with PSS showed no significant difference as compared to controls (MBP: p = 0.240, SBP: p = 0.340, DBP: p = 0.190). Increased plasma ADMA was seen in RA (0.45 ± 0.069 ng/mL) and PSS (0.43 ± 0.060 ng/mL) patients as compared to controls (0.38 ± 0.059 ng/mL). ADMA in RA vs. control was statistically significant (p = 0.022). However, no differences were seen in ADMA in PSS vs. controls. PWV and retinal microvasculature did not differ across the three groups. Conclusions: The prevalence of hypertension in our cohort was very high. Similarly, signs of endothelial dysfunction were seen in autoimmune rheumatic diseases. As hypertension and endothelial dysfunction are important contributing risk factors for cardiovascular diseases, the association of hypertension and endothelial dysfunction should be monitored closely in autoimmune diseases.
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Liang GC, Duan WG, Chen SY, Fang JK. Analysis of the Composition and Anti-Rheumatoid Arthritis Mechanism of Qintengtongbi Decoction Based on Network Pharmacology. Nat Prod Commun 2021. [DOI: 10.1177/1934578x211041421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Qintengtongbi Decoction (QTTBD) is a traditional prescription for rheumatoid arthritis (RA) treatment in Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, southern China's Guangxi Zhuang Autonomous Region. However, there is not yet any analysis on its active compounds or action mechanism for treating RA. Moreover, the prescription has not been investigated from the perspective of network pharmacology. Therefore, this study aimed to analyze the compounds QTTBD and their potential pharmacological effects and the mechanism by which they treat RA via an integrated network pharmacology approach. With the aid of the relevant database tools and research indices, 188 compounds and 272 related drug targets genes/proteins were collected from QTTBD through the compound-target network, and 175 common gene targets between the QTTBD and RA were obtained by Venn 2.1. Finally, the top 10 gene targets and pathways were identified through the protein–protein interaction network, gene ontology, and KEGG pathway analysis: the gene targets include AKT1, IL6, TP53, VEGFA, MAPK3, TNF, CASP3, JUN, EGF, and EGFR; the pathways include oxytocin signaling pathway, amphetamine addiction, graft-versus-host disease, ovarian steroidogenesis, cGMP-PKG signaling pathway, Rap1 signaling pathway, allograft rejection, cytokine–cytokine receptor interaction, regulation of lipolysis in adipocytes and inflammatory mediator regulation of transient receptor potential channels. Therefore, it is concluded that a network pharmacology-based approach can help reveal and clarify the anti-RA role of QTTBD, and provide a scientific basis for further research into the mechanism.
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Affiliation(s)
- Guo-Cheng Liang
- School of Chemistry and Chemical Engineering, Guangxi University, Nanning, China
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
| | - Wen-Gui Duan
- School of Chemistry and Chemical Engineering, Guangxi University, Nanning, China
| | - Shu-Yin Chen
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
| | - Jian-Kang Fang
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, China
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Kessler J, Totoson P, Devaux S, Moretto J, Wendling D, Demougeot C. Animal models to study pathogenesis and treatments of cardiac disorders in rheumatoid arthritis: Advances and challenges for clinical translation. Pharmacol Res 2021; 170:105494. [PMID: 34139344 DOI: 10.1016/j.phrs.2021.105494] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 02/08/2021] [Accepted: 02/11/2021] [Indexed: 11/15/2022]
Abstract
Although cardiac diseases such as acute myocardial infarction, heart failure and arrhythmias are the leading cause of cardiovascular complications in rheumatoid arthritis (RA), their pathogenesis is far from being understood and optimal therapeutic options to treat specifically these disorders in RA are lacking. Preclinical studies on animal models of arthritis can help to decipher the complex link between arthritis and the heart, and to identify critical pathways and novel therapeutic targets. This review presented the available data on cardiac disorders in animal models of RA, as well as the current knowledge on pathophysiology and pharmacology of these disorders. Future directions for translational studies in a cardiorheumatic perspective are proposed.
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Affiliation(s)
- Julie Kessler
- PEPITE EA 4267, FHU INCREASE, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France; Service de Rhumatologie, CHU Minjoz, 25000 Besançon, France
| | - Perle Totoson
- PEPITE EA 4267, FHU INCREASE, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France
| | - Sylvie Devaux
- PEPITE EA 4267, FHU INCREASE, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France
| | - Johnny Moretto
- PEPITE EA 4267, FHU INCREASE, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France
| | - Daniel Wendling
- Service de Rhumatologie, CHU Minjoz, 25000 Besançon, France; EA 4266 " Agents Pathogènes et Inflammation ", EPILAB, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France
| | - Céline Demougeot
- PEPITE EA 4267, FHU INCREASE, Univ. Bourgogne Franche-Comté, F-25000 Besançon, France.
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40
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Kong CY, Wang CL, Niu KJ, Qi W. Prevalence of metabolic syndrome in patients with rheumatoid arthritis in eastern China-A hospital based study. Int J Rheum Dis 2021; 24:1121-1126. [PMID: 34080783 DOI: 10.1111/1756-185x.14148] [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: 12/31/2020] [Revised: 05/07/2021] [Accepted: 05/09/2021] [Indexed: 10/21/2022]
Abstract
OBJECTIVE The purpose of this hospital clinic based study was to evaluate the potential risk factors associated with the prevalence of MetS in RA population. METHODS From January 2015 to October 2018, 717 patients with RA and 717 healthy controls who were treated or performed physical examination in Tianjin First Central Hospital were enrolled in this study. The basic disease diagnoses were recorded. A questionnaire was performed on all participants to assess the demographic details of the RA cohort. Moreover, laboratory indicators related to glucose and lipid metabolism in patients with RA were also detected. The potential risk factors for MetS were also analyzed. RESULTS The prevalence of MetS were 31.2% and 34.2% in case and control groups, respectively (P = .22). There were lower levels of HDL-C, obesity, TG, LDL-C and TC in case group than control group (all P < .05). The hypertension levels in healthy controls was decreased in compared with patients with RA (P < .05). Nevertheless, in patients with RA, complement 3 (OR: 1.02; 95% CI: 1.01-1.03, P = .007) and less glucocorticoids use (OR: 0.63, 95% CI: 0.39-0.99, P = .046) were associated with MetS. CONCLUSION The prevalence of MetS was not associated with RA. Complement 3 may be associated with the higher prevalence of MetS in patients with RA. Glucocorticoids treatment may be associated with MetS.
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Affiliation(s)
| | - Chang-Lei Wang
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Kai-Jun Niu
- Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China.,Health Management Centre, Tianjin Medical University General Hospital, Tianjin, China
| | - Wufang Qi
- Tianjin First Center Hospital, Tianjin, China
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Verhoeven F, Prati C, Chouk M, Demougeot C, Wendling D. Methotrexate and cardiovascular risk in rheumatic diseases:A comprehensive review. Expert Rev Clin Pharmacol 2021; 14:1105-1112. [PMID: 34006152 DOI: 10.1080/17512433.2021.1932461] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Introduction: Management of inflammatory rheumatic diseases has evolved based on improved treatment strategies and better management of comorbidities, specifically cardiovascular risk. Methotrexate is one of the first-line treatments in the management of inflammatory rheumatic diseases, but its cardiovascular effects are poorly understood. The purpose of this review is to assess the cardiovascular impact of methotrexate in inflammatory rheumatic disease.Areas covered: Current knowledge about the mechanism of action of methotrexate on cardiovascular tissue is presented. A review of the literature in the Medline, Cochrane and Embase databases was performed. Current data about the cardiovascular effects of methotrexate in rheumatoid arthritis, psoriatic arthritis, and psoriasis are presented.Expert opinion: Mechanism of action of methotrexate is based on the antagonism of purines. It reduces systemic inflammation and oxidative stress and improves the major cardiovascular risk factors. Methotrexate improves cardiovascular risk in rheumatoid arthritis, psoriasis and psoriatic arthritis, but the mechanisms involved are partially identified. Data are controversial regarding its effects on endothelial function and atherosclerosis. Conversely, in the general population and in patients with HIV infection, methotrexate does not modify cardiovascular outcomes. Thus, methotrexate only improves cardiovascular risk by reducing systemic inflammation, and should not be used to prevent cardiovascular events.
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Affiliation(s)
- Frank Verhoeven
- Department of Rheumatology, Service De Rhumatologie, CHRU De Besançon, Besancon, France.,EA 4267 : "PEPITE", FHU Increase, Université Bourgogne - Franche Comte, UFR Santé, Besancon, France
| | - Clément Prati
- Department of Rheumatology, Service De Rhumatologie, CHRU De Besançon, Besancon, France.,EA 4267 : "PEPITE", FHU Increase, Université Bourgogne - Franche Comte, UFR Santé, Besancon, France
| | - Mickaël Chouk
- Department of Rheumatology, Service De Rhumatologie, CHRU De Besançon, Besancon, France
| | - Céline Demougeot
- EA 4267 : "PEPITE", FHU Increase, Université Bourgogne - Franche Comte, UFR Santé, Besancon, France
| | - Daniel Wendling
- Department of Rheumatology, Service De Rhumatologie, CHRU De Besançon, Besancon, France.,EA 4266 : « EPILAB », Université Bourgogne - Franche Comte, UFR Santé, Besancon, France
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Costello RE, Yimer BB, Roads P, Jani M, Dixon WG. Glucocorticoid use is associated with an increased risk of hypertension. Rheumatology (Oxford) 2021; 60:132-139. [PMID: 32596721 PMCID: PMC7785301 DOI: 10.1093/rheumatology/keaa209] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 03/31/2020] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVES Patients with RA are frequently treated with glucocorticoids (GCs), but evidence is conflicting about whether GCs are associated with hypertension. The aim of this study was to determine whether GCs are associated with incident hypertension in patients with RA. METHODS A retrospective cohort of patients with incident RA and without hypertension was identified from UK primary care electronic medical records (Clinical Practice Research Datalink). GC prescriptions were used to determine time-varying GC use, dose and cumulative dose, with a 3 month attribution window. Hypertension was identified through either: blood pressure measurements >140/90 mmHg, or antihypertensive prescriptions and a Read code for hypertension. Unadjusted and adjusted Cox proportional hazards regression models were fitted to determine whether there was an association between GC use and incident hypertension. RESULTS There were 17 760 patients in the cohort. A total of 7421 (42%) were prescribed GCs during follow-up. The incident rate of hypertension was 64.1 per 1000 person years (95% CI: 62.5, 65.7). The Cox proportional hazards model indicated that recent GC use was associated with a 17% increased hazard of hypertension (hazard ratio 1.17; 95% CI: 1.10, 1.24). When categorized by dose, only doses above 7.5 mg were significantly associated with hypertension. Cumulative dose did not indicate a clear pattern. CONCLUSION Recent GC use was associated with incident hypertension in patients with RA, in particular doses ≥7.5 mg were associated with hypertension. Clinicians need to consider cardiovascular risk when prescribing GCs, and ensure blood pressure is regularly monitored and treated where necessary.
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Affiliation(s)
- Ruth E Costello
- Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, University of Manchester, Manchester
| | - Belay B Yimer
- Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, University of Manchester, Manchester
| | - Polly Roads
- Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, University of Manchester, Manchester
| | - Meghna Jani
- Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, University of Manchester, Manchester.,Department of Rheumatology, Salford Royal NHS Foundation Trust, Salford, UK
| | - William G Dixon
- Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, University of Manchester, Manchester.,Department of Rheumatology, Salford Royal NHS Foundation Trust, Salford, UK
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Madhur MS, Elijovich F, Alexander MR, Pitzer A, Ishimwe J, Van Beusecum JP, Patrick DM, Smart CD, Kleyman TR, Kingery J, Peck RN, Laffer CL, Kirabo A. Hypertension: Do Inflammation and Immunity Hold the Key to Solving this Epidemic? Circ Res 2021; 128:908-933. [PMID: 33793336 PMCID: PMC8023750 DOI: 10.1161/circresaha.121.318052] [Citation(s) in RCA: 124] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Elevated cardiovascular risk including stroke, heart failure, and heart attack is present even after normalization of blood pressure in patients with hypertension. Underlying immune cell activation is a likely culprit. Although immune cells are important for protection against invading pathogens, their chronic overactivation may lead to tissue damage and high blood pressure. Triggers that may initiate immune activation include viral infections, autoimmunity, and lifestyle factors such as excess dietary salt. These conditions activate the immune system either directly or through their impact on the gut microbiome, which ultimately produces chronic inflammation and hypertension. T cells are central to the immune responses contributing to hypertension. They are activated in part by binding specific antigens that are presented in major histocompatibility complex molecules on professional antigen-presenting cells, and they generate repertoires of rearranged T-cell receptors. Activated T cells infiltrate tissues and produce cytokines including interleukin 17A, which promote renal and vascular dysfunction and end-organ damage leading to hypertension. In this comprehensive review, we highlight environmental, genetic, and microbial associated mechanisms contributing to both innate and adaptive immune cell activation leading to hypertension. Targeting the underlying chronic immune cell activation in hypertension has the potential to mitigate the excess cardiovascular risk associated with this common and deadly disease.
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Affiliation(s)
- Meena S. Madhur
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center
- Department of Molecular Physiology and Biophysics, Vanderbilt University
| | - Fernando Elijovich
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Matthew R. Alexander
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center
| | - Ashley Pitzer
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Jeanne Ishimwe
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Justin P. Van Beusecum
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - David M. Patrick
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center
| | - Charles D. Smart
- Department of Molecular Physiology and Biophysics, Vanderbilt University
| | - Thomas R. Kleyman
- Departments of Medicine, Cell Biology, Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Justin Kingery
- Center for Global Health, Weill Cornell Medical College, New York, NY, USA
- Department of Medicine, Weill Bugando School of Medicine, Mwanza, Tanzania
| | - Robert N. Peck
- Center for Global Health, Weill Cornell Medical College, New York, NY, USA
- Department of Medicine, Weill Bugando School of Medicine, Mwanza, Tanzania
- Mwanza Intervention Trials Unit (MITU), Mwanza, Tanzania
| | - Cheryl L. Laffer
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Annet Kirabo
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Department of Molecular Physiology and Biophysics, Vanderbilt University
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Jung R, Wild J, Ringen J, Karbach S, Wenzel P. Innate Immune Mechanisms of Arterial Hypertension and Autoimmune Disease. Am J Hypertens 2021; 34:143-153. [PMID: 32930786 DOI: 10.1093/ajh/hpaa145] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 08/15/2020] [Accepted: 09/14/2020] [Indexed: 12/16/2022] Open
Abstract
The immune system is indispensable in the development of vascular dysfunction and hypertension. The interplay between immune cells and the vasculature, kidneys, heart, and blood pressure regulating nuclei in the central nervous system results in a complex and closely interwoven relationship of the immune system with arterial hypertension. A better understanding of this interplay is necessary for optimized and individualized antihypertensive therapy. Our review article focuses on innate cells in hypertension and to what extent they impact on development and preservation of elevated blood pressure. Moreover, we address the association of hypertension with chronic autoimmune diseases. The latter are ideally suited to learn about immune-mediated mechanisms in cardiovascular disease leading to high blood pressure.
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Affiliation(s)
- Rebecca Jung
- Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany
| | - Johannes Wild
- Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany
- Department of Cardiology, University Medical Center Mainz, Mainz, Germany
| | - Julia Ringen
- Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany
| | - Susanne Karbach
- Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany
- Department of Cardiology, University Medical Center Mainz, Mainz, Germany
- German Center for Cardiovascular Research (DZHK), partner site Rhine-Main, Germany
| | - Philip Wenzel
- Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany
- Department of Cardiology, University Medical Center Mainz, Mainz, Germany
- German Center for Cardiovascular Research (DZHK), partner site Rhine-Main, Germany
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45
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Ferguson LD, Sattar N, McInnes IB. Managing Cardiovascular Risk in Patients with Rheumatic Disease. Med Clin North Am 2021; 105:247-262. [PMID: 33589100 DOI: 10.1016/j.mcna.2020.09.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Individuals with rheumatoid arthritis, systemic lupus erythematosus, or gout have increased risk of cardiovascular disease (CVD) compared with the general population. This risk relates to a combination of traditional cardiovascular risk factors and disease-specific factors. Screening for CVD is important because CVD contributes to significant morbidity and mortality. Management includes tight control of disease activity to reduce inflammation, but with care to minimize use of nonsteroidal anti-inflammatory drugs and prolonged courses of high-dose corticosteroids. Traditional cardiovascular risk factors should be managed with a combination of lifestyle interventions and pharmacotherapy. The decision to start antihypertensive and lipid-lowering therapy should be based on individual CVD risk.
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Affiliation(s)
- Lyn D Ferguson
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
| | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
| | - Iain B McInnes
- Institute of Infection, Immunity and Inflammation, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK
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46
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Figus FA, Piga M, Azzolin I, McConnell R, Iagnocco A. Rheumatoid arthritis: Extra-articular manifestations and comorbidities. Autoimmun Rev 2021; 20:102776. [PMID: 33609792 DOI: 10.1016/j.autrev.2021.102776] [Citation(s) in RCA: 247] [Impact Index Per Article: 61.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 12/27/2020] [Indexed: 12/20/2022]
Abstract
Although synovitis is the pathological hallmark of rheumatoid arthritis (RA), many extra-articular manifestations (EMs) and comorbidities likely occur due to the complex, chronic, inflammatory, and autoimmune features of RA. Cardiovascular (CV) disease is the most common cause of death in patients with RA. Compared to the general population, patients with RA have twice the risk of myocardial infarction and up to 50% increased CV mortality risk. Severe and prolonged disease activity, genetics, and inflammation (e.g. CRP, ACPA, cytokines, matrix-degrading enzymes) play important roles in CV disease and atheroscleroticdamage. The second major cause of death in patients with RA is respiratory disease, which occurs in 30-40% of patients. RA may affect the lung interstitium, airways, and pleurae, while pulmonary vascular involvement is less frequent. Central and peripheral nervous system involvement is usually due to small vessel vasculitis, joint damage, or drug toxicity. There is also evidence that microvascular cerebral damage caused by systemic inflammation is associated with the development of Alzheimer's disease and vascular dementia. Some observational studies have hinted how Disease Modified Anti-Rheumatic Drugs and biologics could reduce the incidence of dementia. Primary gastrointestinal and renal involvements are rare and often relate to drug therapy. To minimize morbidity and mortality, physicians must manage RA disease activity (treat-to-target) and monitor risk factors and concomitant conditions (e.g. smoking cessation; weight regulation; monitoring blood pressure, lipids, thyroid hormone, folic acid and homocysteine; screening for depression, anxiety, atlantoaxial instability, and atherosclerosis). This article aims to provide an overview of the most prevalent and important EMs and comorbidities associated with RA.
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Affiliation(s)
- Fabiana Assunta Figus
- Academic Rheumatology Centre, MFRU and Dipartimento Scienze Cliniche e Biologiche, Università degli Studi di Torino, Torino, Italy
| | - Matteo Piga
- Rheumatology Unit, University Clinic and AOU of Cagliari, Monserrato, Italy
| | - Irene Azzolin
- Academic Rheumatology Centre, MFRU and Dipartimento Scienze Cliniche e Biologiche, Università degli Studi di Torino, Torino, Italy
| | | | - Annamaria Iagnocco
- Academic Rheumatology Centre, MFRU and Dipartimento Scienze Cliniche e Biologiche, Università degli Studi di Torino, Torino, Italy.
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47
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Hansildaar R, Vedder D, Baniaamam M, Tausche AK, Gerritsen M, Nurmohamed MT. Cardiovascular risk in inflammatory arthritis: rheumatoid arthritis and gout. THE LANCET. RHEUMATOLOGY 2021; 3:e58-e70. [PMID: 32904897 PMCID: PMC7462628 DOI: 10.1016/s2665-9913(20)30221-6] [Citation(s) in RCA: 139] [Impact Index Per Article: 34.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The increased risk of cardiovascular morbidity and mortality in rheumatoid arthritis and gout has been increasingly acknowledged in past decades, with accumulating evidence that gout, just as with rheumatoid arthritis, is an independent cardiovascular risk factor. Although both diseases have a completely different pathogenesis, the underlying pathophysiological mechanisms in systemic inflammation overlap to some extent. Following the recognition that systemic inflammation has an important causative role in cardiovascular disease, anti-inflammatory therapy in both conditions and urate-lowering therapies in gout are expected to lower the cardiovascular burden of patients. Unfortunately, much of the existing data showing that urate-lowering therapy has consistent beneficial effects on cardiovascular outcomes in patients with gout are of low quality and contradictory. We will discuss the latest evidence in this respect. Cardiovascular disease risk management for patients with rheumatoid arthritis and gout is essential. Clinical guidelines and implementation of cardiovascular risk management in daily clinical practice, as well as unmet needs and areas for further investigation, will be discussed.
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Affiliation(s)
- Romy Hansildaar
- Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center, Vrije Universiteit Amsterdam and Reade, Amsterdam, Netherlands.,Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands
| | - Daisy Vedder
- Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center, Vrije Universiteit Amsterdam and Reade, Amsterdam, Netherlands.,Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands
| | - Milad Baniaamam
- Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center, Vrije Universiteit Amsterdam and Reade, Amsterdam, Netherlands.,Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands
| | - Anne-Kathrin Tausche
- Department of Rheumatology, University Clinic Carl Gustav Carus at TU Dresden, Dresden, Germany
| | - Martijn Gerritsen
- Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center, Vrije Universiteit Amsterdam and Reade, Amsterdam, Netherlands
| | - Michael T Nurmohamed
- Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center, Vrije Universiteit Amsterdam and Reade, Amsterdam, Netherlands.,Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands
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48
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Atzeni F, Nucera V, Gerratana E, Fiorenza A, Gianturco L, Corda M, Sarzi-Puttini P. Cardiovascular Consequences of Autoimmune Rheumatic Diseases. Curr Vasc Pharmacol 2020; 18:566-579. [PMID: 31985379 DOI: 10.2174/1570161118666200127142936] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Revised: 12/23/2019] [Accepted: 12/28/2019] [Indexed: 12/23/2022]
Abstract
The increased risk of cardiovascular disease (CVD) among patients with autoimmune rheumatic diseases such as rheumatoid arthritis, spondyloarthritis and systemic lupus erythematosus has been extensively documented. Sub-clinical atherosclerosis can be assessed using various non-invasive imaging techniques. However, the mechanisms underlying the higher risk of atherosclerotic CVD in patients with autoimmune rheumatic diseases are not fully known, although they seem to include chronic low-grade systemic inflammation leading to prolonged endothelial activation, accompanied by a pro-thrombotic/pro-coagulant and autoantibody state. Furthermore, sub-clinical atherosclerosis is also influenced by other traditional risk factors for CVD. Including the individual components of the metabolic syndrome (MetS: obesity, impaired glucose metabolism, dyslipidemia and high blood pressure), the degree of which is higher in these patients than in controls. The aim of this narrative review is to discuss the CV manifestations and risk factors involved in the increased risk of CVD among patients with autoimmune rheumatic diseases.
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Affiliation(s)
- Fabiola Atzeni
- Rheumatology Unit, University of Messina, Messina, Italy
| | - Valeria Nucera
- Rheumatology Unit, University of Messina, Messina, Italy
| | | | | | - Luigi Gianturco
- Cardiology Unit, Beato Matteo Hospital, GSD Hospitals, Vigevano, Pavia, Italy
| | - Marco Corda
- Cardiology Unit, Brotzu Hospital, Cagliari, Italy
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49
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Papagoras C, Voulgari PV, Drosos AA. Cardiovascular Disease in Spondyloarthritides. Curr Vasc Pharmacol 2020; 18:473-487. [PMID: 31330576 DOI: 10.2174/1570161117666190426164306] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 04/13/2019] [Accepted: 04/13/2019] [Indexed: 12/15/2022]
Abstract
The spondyloarthritides are a group of chronic systemic inflammatory joint diseases, the main types being ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Evidence accumulating during the last decades suggests that patients with AS or PsA carry an increased risk for cardiovascular disease and cardiovascular death. This risk appears to be mediated by systemic inflammation over and above classical cardiovascular risk factors. The excess cardiovascular risk in those patients has been formally acknowledged by scientific organizations, which have called physicians' attention to the matter. The application by Rheumatologists of new effective anti-rheumatic treatments and treat-to-target strategies seems to benefit patients from a cardiovascular point of view, as well. However, more data are needed in order to verify whether anti-rheumatic treatments do have an effect on cardiovascular risk and whether there are differences among them in this regard. Most importantly, a higher level of awareness of the cardiovascular risk is needed among patients and healthcare providers, better tools to recognize at-risk patients and, ultimately, commitment to address in parallel both the musculoskeletal and the cardiovascular aspect of the disease.
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Affiliation(s)
- Charalampos Papagoras
- 1st Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - Paraskevi V Voulgari
- Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece
| | - Alexandros A Drosos
- Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece
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Peçanha T, Meireles K, Pinto AJ, Rezende DAN, Iraha AY, Mazzolani BC, Smaira FI, Sales ARK, Bonfiglioli K, Sá-Pinto ALD, Lima FR, Irigoyen MC, Gualano B, Roschel H. Increased sympathetic and haemodynamic responses to exercise and muscle metaboreflex activation in post-menopausal women with rheumatoid arthritis. J Physiol 2020; 599:927-941. [PMID: 33180998 DOI: 10.1113/jp280892] [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: 09/30/2020] [Accepted: 11/05/2020] [Indexed: 12/20/2022] Open
Abstract
KEY POINTS Rheumatoid arthritis (RA) patients present exacerbated blood pressure responses to exercise, but little is known regarding the underlying mechanisms involved. This study assessed autonomic and haemodynamic responses to exercise and to the isolated activation of muscle metaboreflex in post-menopausal women with RA. Participants with RA showed augmented pressor and sympathetic responses to exercise and to the activation of muscle metaboreflex. These responses were associated with multiple pro- and anti-inflammatory cytokines and with pain. The results of the present study support the suggestion that an abnormal reflex control of circulation is an important mechanism underlying the exacerbated cardiovascular response to exercise and increased cardiovascular risk in RA. ABSTRACT Studies have reported abnormal cardiovascular responses to exercise in rheumatoid arthritis (RA) patients, but little is known regarding the underlying mechanisms involved. This study assessed haemodynamic and sympathetic responses to exercise and to the isolated activation of muscle metaboreflex in women diagnosed with RA. Thirty-three post-menopausal women diagnosed with RA and 10 matched controls (CON) participated in this study. Mean arterial pressure (MAP), heart rate (HR) and muscle sympathetic nerve activity (MSNA frequency and incidence) were measured during a protocol of isometric knee extension exercise (3 min, 30% of maximal voluntary contraction), followed by post-exercise ischaemia (PEI). Participants with RA showed greater increases in MAP and MSNA during exercise and PEI than CON (ΔMAPexercise = 16 ± 11 vs. 9 ± 6 mmHg, P = 0.03; ΔMAPPEI = 15 ± 10 vs. 5 ± 5 mmHg, P = 0.001; ΔMSNAexercise = 17 ± 14 vs. 7 ± 9 bursts min-1 , P = 0.04; ΔMSNAPEI = 14 ± 10 vs. 6 ± 4 bursts min-1 , P = 0.04). Autonomic responses to exercise showed significant (P < 0.05) association with pro- (i.e. IFN-γ, IL-8, MCP-1 and TNFα) and anti-inflammatory (i.e. IL-1ra and IL-10) cytokines and with pain. In conclusion, post-menopausal women with RA showed augmented pressor and sympathetic responses to exercise and to the activation of muscle metaboreflex. These findings provide mechanistic insights that may explain the abnormal cardiovascular responses to exercise in RA.
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Affiliation(s)
- Tiago Peçanha
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Kamila Meireles
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Ana Jéssica Pinto
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Diego Augusto Nunes Rezende
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Amanda Yuri Iraha
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Bruna Caruso Mazzolani
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Fabiana Infante Smaira
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Allan Robson Kluser Sales
- Heart Institute, Hospital das Clínicas, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil.,D'Or Institute for Research and Education (IDOR), São Paulo, Brazil
| | - Karina Bonfiglioli
- Rheumatology Division, Hospital das Clínicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Ana Lúcia de Sá-Pinto
- Rheumatology Division, Hospital das Clínicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Fernanda Rodrigues Lima
- Rheumatology Division, Hospital das Clínicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Maria Cláudia Irigoyen
- Heart Institute, Hospital das Clínicas, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Bruno Gualano
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil.,Rheumatology Division, Hospital das Clínicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Hamilton Roschel
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil.,Rheumatology Division, Hospital das Clínicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
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