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      Adjunctive Chinese Herbal Products Therapy Reduces the Risk of Ischemic Stroke Among Patients With Rheumatoid Arthritis

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          Abstract

          We performed a retrospective cohort study to investigate the association between the risk of ischemic stroke (IS) and the use of Chinese herbal products (CHP) in combination with western medicine (WM) among patients with rheumatoid arthritis (RA). The data were sourced from the registry for beneficiaries, inpatient and ambulatory care claims, and Registry for Catastrophic Illness from the National Health Insurance Research Database (NHIRD) in Taiwan between 1997 and 2011. Patients, who were newly diagnosed with RA between 1997 and 2010, were classified as the CHP group or non-CHP group depending on the presence of absence the adjunctive use of CHP following a diagnosis of RA. A total of 4,148 RA patients were in both the CHP and non-CHP groups after 1:1 matching. Patients in the CHP group had a significantly lower risk of IS compared to patients in the non-CHP group (adjusted hazard ratio [aHR], 0.67; 95% confidence interval [CI], 0.52–0.86). In the CHP group, patients who used CHP for more than 30 days had a lower risk of IS than their counterparts (aHR: 0.61, 95% CI: 0.40–0.91). Gui-Zhi-Shao-Yao-Zhi-Mu-Tang, Shu-Jin-Huo-Xie-Tang, and Du-Huo-Ji-Sheng-Tang might be associated with a lower risk of IS. Finally, the use of CHP in combination with WM was associated with a decreased risk of IS in patients with RA, especially among those who had used CHP for more than 30 days. A further randomized control trial is required to clarify the casual relationship between these results.

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          Most cited references48

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          The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis

          The objective of this systematic literature review was to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso). Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010–2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data. Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR), 0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to 0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been specifically related to the effects of rofecoxib. Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p<0.001). In PsA/Pso, systemic therapy decreased the risk of all CVEs (RR, 0.75; 95% CI 0.63 to 0.91; p=0.003). In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk. Targeting inflammation with tumour necrosis factor inhibitors or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso, limited evidence suggests that systemic therapies are associated with a decrease in all CVE risk.
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            Explaining how "high-grade" systemic inflammation accelerates vascular risk in rheumatoid arthritis.

            There is intense interest in mechanisms whereby low-grade inflammation could interact with conventional and novel vascular risk factors to promote the atheromatous lesion. Patients with rheumatoid arthritis (RA), who by definition manifest persistent high levels of inflammation, are at greater risk of developing cardiovascular disease. Mechanisms mediating this enhanced risk are ill defined. On the basis of available evidence, we argue here that the systemic inflammatory response in RA is critical to accelerated atherogenesis operating via accentuation of established and novel risk factor pathways. By implication, long-term suppression of the systemic inflammatory response in RA should be effective in reducing risk of coronary heart disease. Early epidemiological observational and clinical studies are commensurate with this hypothesis. By contrast, risk factor modulation with conventional agents, such as statins, may provide unpredictable clinical benefit in the context of uncontrolled systemic inflammatory parameters. Unraveling such complex relationships in which exaggerated inflammation-risk factor interactions are prevalent may elicit novel insights to effector mechanisms in vascular disease generally.
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              AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases. American Heart Association Science Advisory and Coordinating Committee.

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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                04 March 2020
                2020
                : 11
                : 169
                Affiliations
                [1] 1 Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation , Hualien, Taiwan
                [2] 2 School of Post-Baccalaureate Chinese Medicine, Tzu Chi University , Hualien, Taiwan
                [3] 3 Management Office for Health Data, China Medical University Hospital , Taichung, Taiwan
                [4] 4 College of Medicine, China Medical University , Taichung, Taiwan
                [5] 5 Department of Nursing, Asia University , Taichung, Taiwan
                Author notes

                Edited by: Per-Johan Jakobsson, Karolinska Institutet, Sweden

                Reviewed by: Runyue Huang, Guangzhou University of Chinese Medicine, China; Javier Echeverria, Universidad de Santiago de Chile, Chile

                *Correspondence: Nai-Huan Hsiung, laineyhsiung@ 123456gmail.com

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2020.00169
                7064546
                4bef5315-1a1c-416d-bfb4-3826d1ae7854
                Copyright © 2020 Shen, Chiang and Hsiung

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 23 March 2019
                : 07 February 2020
                Page count
                Figures: 2, Tables: 5, Equations: 0, References: 62, Pages: 12, Words: 7147
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                rheumatoid arthritis,ischemic stroke,chinese herbal products,national health insurance research database,traditional chinese medicine

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