Risk of cardiovascular events in people prescribed glucocorticoids with iatrogenic Cushing’s syndrome: cohort study
Cite this as: BMJ 2012;345:e4928
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Fardet and colleagues suggest that iatrogenic corticosteroids are risk factors for cardiovascular disease . I would like to politely disagree with this conclusion. It is highly probable that this analysis reflects the increased cardiovascular risk associated with the disease conditions for which these agents are prescribed. For example, it is well-known that most autoimmune conditions are at an increased risk of cardiovascular disease . Subclinical atherosclerosis is noted in many conditions where chronic inflammation is a patho-physiological factor . On the contrary, short-term corticosteroid prescription does not increase the risk for cardiovascular events, since the prescription is for conditions which do not require chronic suppression of the underlying inflammatory state. This is obvious from the current study which noted that those with iatrogenic Cushing’s syndrome (those who are on long-term treatment) are the individuals who run the higher risk. So the conclusion of the study should have been -- when a decision has been made to prescribe steroids long-term, the cardiovascular risk factors associated with the underlying disease states should be addressed and managed aggressively.
1. Fardet L, Petersen I, Nazareth I. Risk of cardiovascular events in people prescribed glucocorticoids with iatrogenic Cushing's syndrome: cohort study. BMJ. 2012; 345: e4928.
2. Haraoui B, Liu PP, Papp KA. Managing cardiovascular risk in patients with chronic inflammatory diseases. Clin Rheumatol. 2012; 31: 585-94.
3. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352:1685–1695
Competing interests: None declared
Manchester Royal Infirmary, Department of Haematology
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The elegant database analysis by Laurence Fardet et al confirms that patients with iatrogenic Cushing’s syndrome have an increased incidence of cardiovascular complications. This finding can be paralleled with a similar risk increase observed in patients with primary aldosteronism [1,2]. In addition to coronary heart disease and heart failure, patients with primary aldosteronism also have a markedly higher prevalence of atrial fibrillation than otherwise similar patients with essential hypertension. Most of the cardiovascular risk increase in patients with primary aldosteronism, including atrial fibrillation, is probably related to the activation of the mineralocorticoid receptor by aldosterone hypersecretion. Indeed, this risk appears to be reversed by mineralocorticoid receptor blockade or by the normalisation of aldosterone secretion after adrenalectomy .
The mechanism of increased cardiovascular risk certainly differs in patients with iatrogenic Cushing’s syndrome, since synthetic glucocorticoids have a very weak mineralocorticoid activity. However, hypertension and coronary heart disease are two major risk factors of atrial fibrillation  and are more frequent in patients with iatrogenic Cushing’s syndrome, as indicated in the study by Laurence Fardet et al. The risk of atrial fibrillation may therefore be increased in these patients as well, and hypokalemia may also contribute. This would be of importance because atrial fibrillation is associated with a significant morbidity and mortality. It would therefore be interesting to know if the risk of atrial fibrillation is increased in the patients with iatrogenic Cushing's syndrome from the Health Improvement Network. If so, atrial fibrillation may explain part of the observed risk of heart failure and stroke.
1. Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 2005;45:1243-8.
2. Catena C, Colussi G, Nadalini E, Chiuch A, Baroselli S, Lapenna R, et al. Cardiovascular outcomes in patients with primary aldosteronism after treatment. Arch Intern Med 2008;168:80-5.
3. Steichen O, Zinzindohoué F, Plouin PF, Amar L. Outcomes of adrenalectomy in patients with unilateral primary aldosteronism: a review. Horm Metab Res 2012;44:221-7.
4. European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery, Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010;31:2369-429.
Competing interests: None declared
Assistance Publique-Hopitaux de Paris, hôpital Tenon, service de médecine interne, 4 rue de la Chine, F-75020 Paris, France
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