Elsevier

Atherosclerosis

Volume 192, Issue 2, June 2007, Pages 376-383
Atherosclerosis

Use of oral corticosteroids and the risk of acute myocardial infarction

https://doi.org/10.1016/j.atherosclerosis.2006.05.019Get rights and content

Abstract

Introduction

A few epidemiological studies suggested an increased coronary heart disease (CHD) risk with high doses of oral corticosteroids.

Methods

We performed a cohort study with nested case-control analysis to estimate the risk of acute myocardial infarction (AMI) associated with the use of oral corticosteroids by dose and duration. We followed-up 404,183 persons, 50–84 years old, without cancer from the general UK population. After validation of a random sample (confirmation rate of 96%), we included 4795 hospitalised cases of AMI or CHD deaths. We randomly sampled 20,000 controls, frequency matched by sex, age and calendar year. Relative risks were estimated using unconditional logistic regression.

Results

The adjusted OR for AMI in current users of oral corticosteroids compared to non-users was 1.42 (95% CI: 1.17–1.72). The risk during the first 30 days of use (OR = 2.24; 95% CI: 1.56–3.20) was greater than with longer duration (OR = 1.22; 95% CI 0.98–1.52). The risk was more pronounced (OR = 2.15; 95% CI 1.45–3.14) among users of prednisolone equivalent doses >10 mg/day. The dose effect was observed both among patients with and without CHD or COPD/asthma.

Conclusion

These results suggest a small increased risk of AMI with oral corticosteroid use with a greater risk observed among users of high corticosteroid dose.

Introduction

Acute and chronic inflammation plays a role in the pathophysiology of atherosclerosis. Corticosteroids are considered the gold standard for anti-inflammatory treatment. However, the use of oral corticosteroids is associated with cardiovascular adverse effects including dyslipemia, hypertension and glucose intolerance [1]. These effects might predispose treated patients to coronary heart disease (CHD). Both prolonged administration and high-doses of corticosteroids have been reported to accelerate atherosclerosis, although studies evaluating surrogates markers of atherosclerosis have shown conflicting results [2], [3], [4].

Oral corticosteroids are commonly used in the treatment of chronic obstructive pulmonary disease (COPD), asthma, lupus erythematosus, rheumatoid arthritis and organ transplantation. The impact of oral corticosteroids on the cardiovascular system has been documented in patients with these conditions [5], [6], [7], [8]. Despite their widespread use, few epidemiological studies have examined the risk of cardiovascular diseases (CVD) associated with corticosteroids. These studies suggest an increased risk of CVD associated to the use of high doses of corticosteroids [9], [10].

Therefore, we have estimated the effect of oral corticosteroid use, dose, and duration on the risk of acute myocardial infarction (AMI), and examined if this risk is modified by prior history of CHD, arthritis, COPD or asthma, and other risk factors or selected comedications.

Section snippets

Population

We conducted this study in the general population in the United Kingdom covered through the general practice research database (GPRD). The GPRD contains computerized medical information entered systematically by general practitioners (GPs) in the UK and sent anonymously to the Medicines and Healthcare products Regulatory Agency (MHRA). [11] Recorded information includes demographic data, outpatient clinical diagnoses, consultant referrals and hospital admissions, and prescriptions. More than

Results

We included 4795 cases of AMI and 20,000 controls. A majority (65%) were men, 55% were aged 70 years or older, and 44% were fatal cases (n = 1914). A total of 743 (15%) cases and 2364 (12%) controls had ever used oral corticosteroids, and 198 (4%) and 507 (3%) were current users, respectively. Because cases and controls were frequency matched by age and sex, the distribution of characteristics only in the control population according to exposure status is provided in Table 1. Current-users were

Discussion

Oral corticosteroids are widely used in the UK over a broad range of indications for varying duration of time [18]. The prevalence of use in the overall GPRD population has been reported close to 1% although varies substantially with age.

In our study, current use of oral corticosteroids was associated with a modest increase in the risk of fatal and non-fatal AMI. This increased risk was mainly observed during the first month of treatment and was dose-dependent. Use of daily prednisolone

Acknowledgment

We thank the general practitioners for their excellent collaboration and the Boston Collaborative Drug Surveillance Program for providing access to the General Practice Research Database.

References (36)

  • Y. Asanuma et al.

    Premature coronary.artery atherosclerosis in systemic lupus erythematosus

    N Engl J Med

    (2003)
  • S. Manzi et al.

    Prevalence and risk factors of carotid plaque in women with systemic lupus erythematosus

    Arthritis Rheum

    (1999)
  • E. Svenungsson et al.

    Risk factors for cardiovascular disease in systemic lupus erythematosus

    Circulation

    (2001)
  • K. Kalbak

    Incidence of arteriosclerosis in patients with rheumatoid arthritis receiving long-term corticosteroid therapy

    Ann Rheum Dis

    (1972)
  • P.C. Souverein et al.

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

    Heart

    (2004)
  • L. Wei et al.

    Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease

    Ann Intern Med

    (2004)
  • L.A. García Rodríguez et al.

    Use of the UK General Practice Research Database for pharmacoepidemiology

    Br J Clin Pharmacol

    (1998)
  • H. Jick et al.

    Validation of information recorded on general practitioner based computerised data resource in the United Kingdom

    BMJ

    (1991)
  • Cited by (0)

    View full text