CARDIOVASCULAR MEDICINE

Use of oral glucocorticoids and risk of cardiovascular and cerebrovascular disease in a population based case–control study

P C Souverein¹, A Berard², T P Van Staa^1,3, C Cooper³, A C G Egberts¹, H G M Leufkens¹, B R Walker⁴

¹ Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht, the Netherlands
² Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada
³ Medical Research Council, Environmental Epidemiology Unit, Southampton University Hospital, Southampton, UK
⁴ Department of Medical Sciences, Endocrinology Unit, University of Edinburgh, Edinburgh, UK

Correspondence to:
Correspondence to:
Dr P C Souverein
Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, PO Box 80082, 3508 TB Utrecht, Netherlands; P.C.Souverein{at}pharm.uu.nl

Objective: To assess whether use of oral glucocorticoids is associated with cardiovascular and cerebrovascular morbidity.

Design and setting: Nested case–control study within a cohort of patients ( 50 years old) with at least one prescription for oral or non-systemic glucocorticoids. Data were from the general practice research database.

Patients: 50 656 patients were identified with a first record for ischaemic heart disease (International classification of diseases, ninth revision (ICD-9) codes 410, 411, 413, and 414), ischaemic stroke or transient ischaemic attack (ICD-9 codes 430–436), or heart failure (ICD-9 code 428) between 1988 and 1998. One control was matched to each case by sex, age, general practice, underlying disease, and calendar time.

Main outcome measure: Odds ratio (OR) of cardiovascular or cerebrovascular events in patients using oral glucocorticoids compared with non-users.

Results: There was a significant association between ever use of oral glucocorticoids and any cardiovascular or cerebrovascular outcome (adjusted OR 1.25, 95% confidence interval (CI) 1.21 to 1.29). The association was stronger for current use of oral glucocorticoids than for recent or past use. Among current users, the highest ORs were observed in the group with the highest average daily dose, although the dose–response relation was not continuous. Current use was associated with an increased risk of heart failure (adjusted OR 2.66, 95% CI 2.46 to 2.87), which was consistent between patients with rheumatoid arthritis, patients with chronic obstructive pulmonary disease, and patients without either of the two conditions. Also, current use was associated with a smaller increased risk of ischaemic heart disease (OR 1.20, 95% CI 1.11 to 1.29).

Conclusions: Oral glucocorticoid use was identified as a risk factor for heart failure. However, the evidence remains observational and only a randomised controlled trial of glucocorticoid treatment versus other disease modifying agents is likely to distinguish the importance of the underlying disease activity from its treatment in predicting cardiovascular outcomes.

Abbreviations: BMI, body mass index; CI, confidence interval; COPD, chronic obstructive pulmonary disease; GPRD, general practice research database; ICD-9, International classification of diseases, ninth revision; NSAIDs, non-steroidal anti-inflammatory drugs; OR, odds ratio; RA, rheumatoid arthritis

Keywords: cardiovascular disease; case–control study; oral glucocorticoids; pharmacoepidemiology

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Oral glucocorticoid treatment, heart failure and atherosclerotic cardiovascular disease

Paul G Cohen

Online, 20 Dec 2004 [Full text]