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      Glucocorticoid use is associated with an increased risk of hypertension

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          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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          Most cited references30

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          Data Resource Profile: Clinical Practice Research Datalink (CPRD)

          The Clinical Practice Research Datalink (CPRD) is an ongoing primary care database of anonymised medical records from general practitioners, with coverage of over 11.3 million patients from 674 practices in the UK. With 4.4 million active (alive, currently registered) patients meeting quality criteria, approximately 6.9% of the UK population are included and patients are broadly representative of the UK general population in terms of age, sex and ethnicity. General practitioners are the gatekeepers of primary care and specialist referrals in the UK. The CPRD primary care database is therefore a rich source of health data for research, including data on demographics, symptoms, tests, diagnoses, therapies, health-related behaviours and referrals to secondary care. For over half of patients, linkage with datasets from secondary care, disease-specific cohorts and mortality records enhance the range of data available for research. The CPRD is very widely used internationally for epidemiological research and has been used to produce over 1000 research studies, published in peer-reviewed journals across a broad range of health outcomes. However, researchers must be aware of the complexity of routinely collected electronic health records, including ways to manage variable completeness, misclassification and development of disease definitions for research.
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            The table 2 fallacy: presenting and interpreting confounder and modifier coefficients.

            It is common to present multiple adjusted effect estimates from a single model in a single table. For example, a table might show odds ratios for one or more exposures and also for several confounders from a single logistic regression. This can lead to mistaken interpretations of these estimates. We use causal diagrams to display the sources of the problems. Presentation of exposure and confounder effect estimates from a single model may lead to several interpretative difficulties, inviting confusion of direct-effect estimates with total-effect estimates for covariates in the model. These effect estimates may also be confounded even though the effect estimate for the main exposure is not confounded. Interpretation of these effect estimates is further complicated by heterogeneity (variation, modification) of the exposure effect measure across covariate levels. We offer suggestions to limit potential misunderstandings when multiple effect estimates are presented, including precise distinction between total and direct effect measures from a single model, and use of multiple models tailored to yield total-effect estimates for covariates.
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              EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update.

              Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.
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                Author and article information

                Journal
                Rheumatology (Oxford)
                Rheumatology (Oxford)
                brheum
                Rheumatology (Oxford, England)
                Oxford University Press
                1462-0324
                1462-0332
                January 2021
                27 June 2020
                27 June 2020
                : 60
                : 1
                : 132-139
                Affiliations
                [1 ] Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, University of Manchester , Manchester
                [2 ] Department of Rheumatology, Salford Royal NHS Foundation Trust , Salford, UK
                Author notes
                Correspondence to: Ruth Costello, Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, Manchester M13 9PT, UK. E-mail: ruth.costello@ 123456manchester.ac.uk
                Author information
                http://orcid.org/0000-0003-2709-6666
                http://orcid.org/0000-0002-1487-277X
                http://orcid.org/0000-0001-5881-4857
                Article
                keaa209
                10.1093/rheumatology/keaa209
                7785301
                32596721
                db2f3c99-d501-4a57-8c66-2f3403cbd49e
                © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.

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

                History
                : 13 December 2019
                : 31 March 2020
                Page count
                Pages: 8
                Funding
                Funded by: Centre for Epidemiology Versus Arthritis;
                Award ID: 21755
                Funded by: National Institute for Health Research Manchester Biomedical Research Centre;
                Categories
                Clinical Science
                AcademicSubjects/MED00360

                Rheumatology
                rheumatoid arthritis,cardiovascular,epidemiology,immunosuppressants,primary care rheumatology

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