Oral glucocorticoids and incidence of hypertension in people with chronic inflammatory diseases: a population-based cohort study

Teumzghi F Mebrahtu, Ann W Morgan, Robert M West, Paul M Stewart, Mar Pujades-Rodriguez, Teumzghi F Mebrahtu, Ann W Morgan, Robert M West, Paul M Stewart, Mar Pujades-Rodriguez

Abstract

Background: Only a few population-based studies have examined the association between glucocorticoids and hypertension, with inconsistent results. We aimed to investigate the effect of oral glucocorticoids on incidence of hypertension in adults with chronic inflammatory diseases.

Methods: We analyzed electronic health records from 389 practices in England during 1998-2017 of adults diagnosed with any of 6 chronic inflammatory diseases but with no previous diagnosis of hypertension. We used glucocorticoid prescription data to construct time-variant daily and cumulative variables of prednisolone-equivalent dose (cumulated from 1 year before the start of follow-up) and estimated incidence rates and adjusted hazard ratios (HRs) for hypertension using Cox regression analysis.

Results: Among 71 642 patients in the cohort, 24 896 (34.8%) developed hypertension during a median follow-up of 6.6 years. The incidence rate of hypertension was 46.7 (95% confidence interval [CI] 46.0-47.3) per 1000 person-years. Incidence rates increased with higher cumulative glucocorticoid prednisolone-equivalent dose, from 44.4 per 1000 person-years in periods of nonuse to 45.3 per 1000 person-years for periods with between > 0.0 and 959.9 mg (HR 1.14, 95% CI 1.09-1.19), to 49.3 per 1000 person-years for periods with 960-3054.9 mg (HR 1.20, 95% CI 1.14-1.27), and to 55.6 per 1000 person-years for periods with ≥ 3055 mg (HR 1.30, 95% CI 1.25-1.35). Cumulative effects were seen for the 6 diseases studied, but dose-response effects were not found for daily dose.

Interpretation: Cumulative dose of oral glucocorticoids was associated with increased incidence of hypertension, suggesting that blood pressure should be monitored closely in patients routinely treated with these drugs. Given that glucocorticoids are widely prescribed, the associated health burden could be high. Trial registration: ClinicalTrials. gov, no. NCT03760562.

Conflict of interest statement

Competing interests: Ann Morgan reports receiving consulting fees for work in relation to giant cell arteritis for Roche, Chugai, GlaxoSmithKline, Sanofi and Regeneron. No other competing interests were declared.

© 2020 Joule Inc. or its licensors.

Figures

Figure 1:
Figure 1:
Time-variant cumulative prednisolone-equivalent dose of oral glucocorticoids and the risk of hypertension by type of chronic inflammatory disease. Note: estimates adjusted for age, index of multiple deprivation, non-oral glucocorticoids (inhaled, nasal, intramuscular, intra-articular, topical or rectal), comorbidities (cardiovascular disease, chronic kidney disease and scleroderma) and time-variant inflammatory chronic disease. CI = confidence interval, HR = hazard ratio.
Figure 2:
Figure 2:
Time-variant daily prednisolone-equivalent dose of oral glucocorticoids and the risk of hypertension by type of chronic inflammatory disease. Note: estimates adjusted for age, index of multiple deprivation, non-oral glucocorticoid use (inhaled, nasal, intramuscular, intra-articular, topical or rectal), comorbidities (cardiovascular disease, chronic kidney disease and scleroderma) and time-variant chronic inflammatory disease. CI = confidence interval, HR = hazard ratio.

References

    1. Hypertension in adults: diagnosis and management: clinical guideline [CG127]. London (UK): National institute for Health and Care Excellence (NICE); 2011. Available: (accessed 2018 July 17).
    1. Kearney PM, Whelton M, Reynolds K, et al. Global burden of hypertension: analysis of worldwide data. Lancet 2005;365:217–23.
    1. Rice JB, White AG, Scarpati LM, et al. Long-term systemic corticosteroid exposure: a systematic literature review. Clin Ther 2017;39:2216–29.
    1. Pivonello R, Isidori AM, De Martino MC, et al. Complications of Cushing’s syndrome: state of the art. Lancet Diabetes Endocrinol 2016;4:611–29.
    1. Fardet L, Petersen I, Nazareth I. Prevalence of long-term oral glucocorticoid prescriptions in the UK over the past 20 years. Rheumatology 2011;50:1982–90.
    1. Dasgupta B, Borg FA, Hassan N, et al. BSR and BHPR guidelines for the management of giant cell arteritis. Rheumatology 2010;49:1594–7.
    1. Dejaco C, Singh YP, Perel P, et al. 2015 recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis 2015;74:1799–807.
    1. Gordon C, Amissah-Arthur MB, Gayed M, et al. The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults. Rheumatology (Oxford) 2018;57:e1–45.
    1. Hellmich B, Agueda A, Monti S, et al. 2018 update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis 2020;79:19–30.
    1. Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019;68(Suppl 3):s1–s106.
    1. Ntatsaki E, Carruthers D, Chakravarty K, et al. BSR and BHPR guideline for the management of adults with ANCA-associated vasculitis. Rheumatology (Oxford) 2014;53:2306–9.
    1. Da Silva JA, Jacobs JW, Kirwan JR, et al. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data. Ann Rheum Dis 2006;65:285–93.
    1. Lee MS, Chang CH, Lin RY, et al. Risks of hypertension associated with cyclosporine, nonsteroidal anti-inflammatory drugs, and systemic glucocorticoids in patients with psoriasis: a nationwide population-based nested case-control study in Taiwan. Pharmacoepidemiol Drug Saf 2016;25:133–40.
    1. Bloechliger M, Reinau D, Spoendlin J, et al. Adverse events profile of oral corticosteroids among asthma patients in the UK: cohort study with a nested case-control analysis. Respir Res 2018;19:75.
    1. Zazzali JL, Broder MS, Omachi TA, et al. Risk of corticosteroid-related adverse events in asthma patients with high oral corticosteroid use. Allergy Asthma Proc 2015;36:268–74.
    1. Herrett E, Gallagher AM, Bhaskaran K, et al. Data resource profile: Clinical Practice Research Datalink (CPRD). Int J Epidemiol 2015;44:827–36.
    1. Smith T, Noble M, Noble S, et al. The English indices of deprivation 2015. London (UK): Department for Communities and Local Government; 2015.
    1. Mathur R, Bhaskaran K, Chaturvedi N, et al. Completeness and usability of ethnicity data in UK-based primary care and hospital databases. J Public Health (Oxf) 2014;36:684–92.
    1. Glucocorticoid therapy: glucocorticoid and mineralocorticoid activity. London (UK): National institute for Health and Care Excellence (NICE); 2018. Available: (accessed 2018 May 30).
    1. Suissa S. Immortal time bias in pharmaco-epidemiology. Am J Epidemiol 2008;167:492–9.
    1. Movahedi M, Costello R, Lunt M, et al. Oral glucocorticoid therapy and all-cause and cause-specific mortality in patients with rheumatoid arthritis: a retrospective cohort study. Eur J Epidemiol 2016;31:1045–55.
    1. Mebrahtu TF, Morgan AW, Keeley A, et al. Dose dependency of iatrogenic glucocorticoid excess and adrenal insufficiency and mortality: a cohort study in England. J Clin Endocrinol Metab 2019. April 22 pii: jc.2019–00153. 10.1210/jc.2019-00153 [Epub ahead of print].
    1. Wu J, Keeley A, Mallen C, et al. Incidence of infections associated with oral glucocorticoid dose in people diagnosed with polymyalgia rheumatica or giant cell arteritis: a cohort study in England. CMAJ 2019;191:E680–88.
    1. Textor J, Hardt J, Knuppel S. DAGitty: a graphical tool for analyzing causal diagrams. Epidemiology 2011;22:745.
    1. Ross EJ, Linch DC. Cushing’s syndrome — killing disease: discriminatory value of signs and symptoms aiding early diagnosis. Lancet 1982;320:646–9.
    1. Huscher D, Thiele K, Gromnica-Ihle E, et al. Dose-related patterns of glucocorticoid-induced side effects. Ann Rheum Dis 2009;68:1119–24.

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