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      Cardiovascular outcomes in patients with co-existing coronary artery disease and rheumatoid arthritis : A systematic review and meta-analysis

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          Abstract

          Background:

          Through this analysis, we aimed to systematically compare the cardiovascular outcomes observed in patients with co-existing coronary artery disease (CAD) and rheumatoid arthritis (RA).

          Methods:

          Mendeley, Web of Science (WOS), MEDLINE, Cochrane central, EMBASE, Google scholar, and http://www.ClinicalTrials.gov were searched for English-based publications on CAD and RA. Selective cardiovascular outcomes were the endpoints in this analysis. The statistical software RevMan 5.3 was used for data assessment. Risk ratios (RR) with 95% confidence intervals (CI) were used to represent each subgroup analysis.

          Results:

          One thousand four hundred forty six (1446) participants had co-existing CAD and RA whereas 205,575 participants were in the control group (only CAD without RA). This current analysis showed that the risk of asymptomatic or stable angina was similar in CAD patients with versus without RA (RR: 0.98, 95% CI: 0.84 – 1.14; P = .78). However, all-cause mortality (RR: 1.47, 95% CI: 1.34 – 1.61; P = 0.00001), cardiac death (RR: 1.51, 95% CI: 1.05 – 2.17; P = .03) and congestive heart failure (RR: 1.41, 95% CI: 1.27 – 1.56; P = .00001) were significantly higher in CAD patients with RA. However, multi-vessel disease (RR: 2.03, 95% CI: 0.57 – 7.26; P = .28), positive stress test (RR: 1.69, 95% CI: 0.70 – 4.08; P = .24), and ischemic events (RR: 1.18, 95% CI: 0.81 – 1.71; P = .40) were similar in both groups. The risk for myocardial infarction, repeated revascularization, and the probability of patients undergoing percutaneous coronary intervention (PCI) (RR: 1.20, 95% CI: 0.75 – 1.93; P = .45) were also similar in CAD patients with versus without RA. When we considered outcomes only in those patients who underwent revascularization by PCI, all-cause mortality (RR: 1.43, 95% CI: 1.29 – 1.60; P = .00001) was still significantly higher in CAD patients with RA.

          Conclusions:

          This analysis showed a significantly higher mortality risk in CAD patients with RA when compared to the control group. Congestive heart failure also significantly manifested more in CAD patients with co-existing RA. However, the risks all the other cardiovascular outcomes were similar in both groups. Nevertheless, due to the several limitations of this analysis, this hypothesis should be confirmed in forthcoming trials based on larger numbers of CAD patients with co-existing RA.

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          Most cited references31

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          Endothelial dysfunction: the early predictor of atherosclerosis

          Abstract Since the discovery in the 1980s that nitric oxide (NO) is in fact the elusive endothelium-derived relaxing factor, it has become evident that NO is not only a major cardiovascular signalling molecule, but that changes in its bioavailability are crucial in determining whether atherosclerosis will develop or not. Sustained high levels of harmful circulating stimuli associated with cardiovascular risk factors such as diabetes mellitus elicit responses in endothelial cells that appear sequentially, namely endothelial cell activation and endothelial dysfunction (ED). ED, characterised by reduced NO bioavailability, is now recognised by many as an early, reversible precursor of atherosclerosis. The pathogenesis of ED is multifactorial; however, oxidative stress appears to be the common underlying cellular mechanism in the ensuing loss of vaso-active, inflammatory, haemostatic and redox homeostasis in the body’s vascular system. The role of ED as a pathophysiological link between early endothelial cell changes associated with cardiovascular risk factors and the development of ischaemic heart disease is of importance to basic scientists and clinicians alike.
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            Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial.

            Rheumatoid arthritis is characterised by inflammatory synovitis, articular destruction, and accelerated atherogenesis. HMG-CoA (3-hydroxy-3-methylglutarylcoenzyme A) reductase inhibitors (statins) mediate clinically significant vascular risk reduction in patients without inflammatory disease and might have immunomodulatory function. We postulated that statins might reduce inflammatory factors in rheumatoid arthritis and modify surrogates for vascular risk. 116 patients with rheumatoid arthritis were randomised in a double-blind placebo-controlled trial to receive 40 mg atorvastatin or placebo as an adjunct to existing disease-modifying antirheumatic drug therapy. Patients were followed up over 6 months and disease activity variables and circulating vascular risk factors were measured. Coprimary outcomes were change in disease activity score (DAS28) and proportion meeting EULAR (European League Against Rheumatism) response criteria. Analysis was by intention to treat. At 6 months, DAS28 improved significantly on atorvastatin (-0.5, 95% CI -0.75 to -0.25) compared with placebo (0.03, -0.23 to 0.28; difference between groups -0.52, 95% CI -0.87 to -0.17, p=0.004). DAS28 EULAR response was achieved in 18 of 58 (31%) patients allocated atorvastatin compared with six of 58 (10%) allocated placebo (odds ratio 3.9, 95% CI 1.42-10.72, p=0.006). C-reactive protein and erythrocyte sedimentation rate declined by 50% and 28%, respectively, relative to placebo (p<0.0001, p=0.005, respectively). Swollen joint count also fell (-2.69 vs -0.53; mean difference -2.16, 95% CI -3.67 to -0.64, p=0.0058). Adverse events occurred with similar frequency in patients allocated atorvastatin and placebo. These data show that statins can mediate modest but clinically apparent anti-inflammatory effects with modification of vascular risk factors in the context of high-grade autoimmune inflammation.
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              Systematic review and meta-analysis: anti-tumor necrosis factor α therapy and cardiovascular events in rheumatoid arthritis.

              Control of rheumatoid arthritis (RA) may reduce the risk of cardiovascular events. We sought to systematically assess the association between anti-tumor necrosis factor α (anti-TNFα) therapy in RA and cardiovascular event rates. Observational cohorts and randomized controlled trials (RCTs) reporting on cardiovascular events (all events, myocardial infarction [MI], congestive heart failure, and cerebrovascular accident [CVA]) in RA patients treated with anti-TNFα therapy compared to traditional disease-modifying antirheumatic drugs were identified from a search of PubMed (1950 to November 2009), EMBase (1980 to November 2009), and conference abstracts. Relative risks (RRs) or hazard ratios and 95% confidence intervals (95% CIs) were extracted. If the incidence was reported, additional data were extracted to calculate an incidence density ratio and its variance. The systematic review and meta-analysis include 16 and 11 publications, respectively. In cohort studies, anti-TNFα therapy was associated with a reduced risk for all cardiovascular events (pooled adjusted RR 0.46; 95% CI 0.28, 0.77), MI (pooled adjusted RR 0.81; 95% CI 0.68, 0.96), and CVA (pooled adjusted RR 0.69; 95% CI 0.53, 0.89). Meta-analysis of RCTs also produced a point estimate indicating lower risk of cardiovascular events, but this was not statistically significant (pooled RR 0.85; 95% CI 0.28, 2.59). Anti-TNFα therapy is associated with a reduced risk of all cardiovascular events, MI, and CVA in observational cohorts. There was heterogeneity among cohort studies and possible publication bias. The point estimate of the effect from RCTs is underpowered with wide 95% CIs, and cardiovascular events were secondary outcomes, but RCTs also demonstrated a trend toward decreased risk. Copyright © 2011 by the American College of Rheumatology.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                April 2020
                03 April 2020
                : 99
                : 14
                : e19658
                Affiliations
                Department of Cardiology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, P. R. China.
                Author notes
                []Correspondence: Hong Wang, Department of Cardiology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, P. R. China (e-mail: iriswh2014@ 123456163.com ).
                Article
                MD-D-19-07466 19658
                10.1097/MD.0000000000019658
                7440102
                32243398
                6414f967-a463-49fb-bc86-740a0b59122f
                Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0.

                History
                : 22 September 2019
                : 17 February 2020
                : 17 February 2020
                Categories
                3400
                Research Article
                Systematic Review and Meta-Analysis
                Custom metadata
                TRUE

                cardiovascular outcomes,coronary artery disease,mortality,percutaneous coronary intervention,revascularization,rheumatoid arthritis

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