Joint Bone Spine 78 (2011) 23–30 Review Cardiovascular risk induced by low-dose corticosteroids in rheumatoid arthritis: A systematic literature review Adeline Ruyssen-Witrand a,∗ , Bruno Fautrel b , Alain Saraux c , Xavier Le Loët d , Thao Pham e a Service de rhumatologie B, hôpital Cochin, AP–HP, université Paris-V René-Descartes, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France b Hôpital Pitié-Salpêtrière, AP–HP, université Paris-VI Pierre-et-Marie-Curie, 47-83, boulevard de l’Hôpital, 75651 Paris cedex 13, France c Hôpital de la Cavale Blanche, CHU de Brest, boulevard Tanguy-Prigent, 29609 Brest, France d Rouen university Hospital and Inserm U905 (IFRMP23), University of Rouen, 1, rue de Germont, 76031 Rouen cedex, France e Hôpital de la Conception, AP–HM, 147, boulevard Baille, 13385 Marseille cedex 05, France article info Article history: Accepted 3 February 2010 Available online 14 May 2010 Keywords: Corticosteroids Cardiovascular disease Rheumatoid arthritis Treatment Epidemiology abstract Objectives: To assess the association between cardiovascular (CV) risk and low-dose corticosteroids (LD- CT, defined as a daily dose < 10 mg/day of prednisone) in rheumatoid arthritis (RA) patients. Methods: Data source: A systematic review of the literature up to June 2009 was performed. Data extrac- tion: (1) cardiovascular risk factors: high blood pressure, glycemia and lipid profile, carotid intima-media thickness, pulse-wave velocity, ventricular function; (2) “hard” outcomes: heart failure (HF), stroke, myocardial infarction (MI) or mortality. Data analysis: descriptive, comparing CV risk between LD-CT- treated RA patients and LD-CT-non-treated RA patients. Results: Of the 1138 screened reports, the literature search identified 37 assessing CV risk in LD-CT treated RA. The analysis showed a protective effect on serum lipid profile, an increase of insulin resistance or glycemia, probably no effect on blood pressure, no effect on atherosclerosis, discrepancies regarding arterial stiffness and no effect on ventricular function or heart rate variability. An association of LD-CT with major CV events was found in 4/6 studies. This included MI (HR = 1.7 [1.2–2.3]), stroke (OR = 4.36 [1.60–11.90] for LDC between 6 and 10 mg/day), mortality (HR = 2.03 [1.25-3.32]) and a composite index of CV events (in the group of rheumatoid factor positive RA, HR = 2.21 [1.22–4.00]). Two studies did not find any significant association between LD-CT exposure and mortality (OR = 2.25 [0.29–102.5]) or a composite index of CV events (OR = 1.3 [0.8–2.0]). Conclusion: Although the literature review showed poor association between LDC exposure and CV risk factors, a trend of increasing major CV events was identified. © 2010 Société franc ¸ aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved. Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to severe joint destruction. Beside structural evolution, patients with RA are at risk of developing cardiovascular (CV) dis- eases including myocardial infarction (MI), heart failure (HF), as well as increased CV mortality [1–3]. Chronic inflammation that occurs in this population is believed to contribute to the increased risk [4–6]. Corticosteroids (CT) are powerful anti-inflammatory agents and have been used since the 1950s in the symptomatic treatment of RA. However, it is known that long-term CT use at high dose have considerable toxicity including effects on blood pressure, insulin resistance, lipid profile, body weight and fat distribution [7,8] that might significantly increase CV risk [9,10]. The risk of CV ∗ Corresponding author. Tel.: +33158412562; fax: +335843549256. E-mail address: adruyssen@hotmail.com (A. Ruyssen-Witrand). events associated with CT has already been demonstrated and is dose-dependant [11]. Therefore, alternative treatment approaches have been developed in RA, using conventional disease-modifying antirheumatic drugs (DMARDs) and more recently biologic agents, which can control RA activity and thus enable dose reduction of CT. CT may also have cardioprotective effects mediated by their anti-inflammatory and antiproliferative actions in the vessel wall [12,13]. However the CV risk with CT use < 10 mg per day has not been clearly demonstrated and based on its beneficial effects of CT in controlling chronic inflammation, low-dose CT (LD-CT) on CV risk is still a subject of contro- versy. The aim of this study is to assess through a systematic literature review the potential association between CV risk and the use of long-term LD-CT defined as an average daily dose below 10 mg per day, in RA. 1297-319X/$ – see front matter © 2010 Société franc ¸ aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved. doi:10.1016/j.jbspin.2010.02.040