Taking Glucocorticoids by Prescription Is Associated with Subsequent Cardiovascular Disease

  1. Li Wei, MB, MSc;
  2. Thomas M. MacDonald, MD, FRCPE; and
  3. Brian R. Walker, MD, FRCPE
  1. From Ninewells Hospital and Medical School, Dundee, Scotland, and University of Edinburgh School of Molecular and Clinical Medicine and Western General Hospital, Edinburgh, Scotland, United Kingdom.

    Abstract

    Background: Glucocorticoids have adverse systemic effects, including obesity, hypertension, and hyperglycemia, that may predispose to cardiovascular disease. The effect of glucocorticoid use on cardiovascular disease has not been quantified.

    Objective: To test the hypothesis that users of exogenous glucocorticoids have an increased risk for cardiovascular disease.

    Design: A cohort study using a record linkage database.

    Setting: Tayside, Scotland, United Kingdom.

    Patients: 68 781 glucocorticoid users and 82 202 nonusers without previous hospitalization for cardiovascular disease who were studied between 1993 and 1996.

    Measurements: The average daily dose of glucocorticoid exposure during follow-up was categorized as low (inhaled, nasal, and topical only), medium (oral, rectal, or parenteral <7.5 mg of prednisolone equivalent), or high (≥7.5 mg of prednisolone equivalent). Poisson regression model, sensitivity analysis, and propensity score methods were used to investigate the asso- ciation between glucocorticoid exposure and cardiovascular outcome.

    Results: 4383 cardiovascular events occurred in 257 487 person-years of follow-up for a rate of 17.0 (95% CI, 16.5 to 17.5) per 1000 person-years in the comparator group, and 5068 events occurred in 212 287 person-years for a rate of 23.9 (CI, 23.2 to 24.5) per 1000 person-years in the group exposed to glucocorticoids (22.1, 27.2, and 76.5 in low, medium, and high groups, respectively). The absolute risk difference was 6.9 (CI, 6.0 to 7.7) per 1000 person-years (5.1, 10.1, and 59.4, respectively). After adjustment for known covariates, the relative risk for a cardiovascular event in patients receiving high-dose glucocorticoids was 2.56 (CI, 2.18 to 2.99).

    Limitations: Because the data were observational, residual confounding cannot be excluded.

    Conclusion: Treatment with high-dose glucocorticoids seemed to be associated with increased risk for cardiovascular disease.

    Article and Author Information

    • Acknowledgments: The MEMO database is part of the U.K. Medical Research Council Health Services Research Collaboration.

    • Grant Support: By the Chief Scientist Office of the Scottish Executive (research grant CZG/4/1/36). Dr. Walker is a British Heart Foundation Senior Research Fellow.

    • Potential Financial Conflicts of Interest: Expert testimony: T.M. MacDonald (U.K. Committee on Safety of Medicines).

    • Requests for Single Reprints: Thomas M. MacDonald, MD, FRCPE, Medicines Monitoring Unit, Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, Scotland DD1 9SY, United Kingdom; e-mail, t.m.macdonald{at}dundee.ac.uk.

    • Current Author Addresses: Drs. Wei and MacDonald: Medicines Monitoring Unit, Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, Scotland DD1 9SY, United Kingdom.

    • Dr. Walker: University of Edinburgh, Endocrinology Unit, School of Molecular and Clinical Medicine, Western General Hospital, Edinburgh, Scotland EH4 2XU, United Kingdom.

    • Author Contributions: Conception and design: L. Wei, T.M. MacDonald, B.R. Walker.

    • Analysis and interpretation of the data: L. Wei, T.M. MacDonald, B.R. Walker.

    • Drafting of the article: L. Wei, T.M. MacDonald, B.R. Walker.

    • Critical revision of the article for important intellectual content: L. Wei, T.M. MacDonald, B.R. Walker.

    • Final approval of the article: L. Wei, T.M. MacDonald, B.R. Walker.

    • Provision of study materials or patients: L. Wei, T.M. MacDonald.

    • Statistical expertise: L. Wei, T.M. MacDonald.

    • Obtaining of funding: L. Wei, T.M. MacDonald, B.R. Walker.

    • Administrative, technical, or logistic support: L. Wei, T.M. MacDonald.

    • Collection and assembly of data: L. Wei, T.M. MacDonald.

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    Summary for Patients

    • Summaries for Patients:Glucocorticoid Medications and the Risk for Cardiovascular Disease Ann Intern Med November 16, 2004 141:I-58
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    1. Ann Intern Med November 16, 2004 vol. 141 no. 10 764-770
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