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Arthritis & Rheumatism (Arthritis Care & Research) Vol. 59, No. 12, December 15, 2008, pp 1690 –1697 DOI 10.1002/art.24092 © 2008, American College of Rheumatology

ORIGINAL ARTICLE

Risk of Cardiovascular Mortality in Patients With Rheumatoid Arthritis: A Meta-Analysis of Observational Studies
˜ J. ANTONIO AVINA-ZUBIETA,1 HYON K. CHOI,1 MOHSEN SADATSAFAVI,2 MAHYAR ETMINAN,2 JOHN M. ESDAILE,1 AND DIANE LACAILLE1

Objective. To determine the magnitude of risk of cardiovascular mortality in patients with rheumatoid arthritis (RA) compared with the general population through a meta-analysis of observational studies. Methods. We searched Medline, EMBase, and Lilacs databases from their inception to July 2005. Observational studies that met the following criteria were assessed by 2 researchers: 1) prespecified RA definition, 2) clearly defined cardiovascular disease (CVD) outcome, including ischemic heart disease (IHD) and cerebrovascular accidents (CVAs), and 3) reported standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs). We calculated weighted–pooled summary estimates of SMRs (meta-SMRs) for CVD, IHD, and CVAs using the random-effects model, and tested for heterogeneity using the I2 statistic. Results. Twenty-four studies met the inclusion criteria, comprising 111,758 patients with 22,927 cardiovascular events. Overall, there was a 50% increased risk of CVD death in patients with RA (meta-SMR 1.50, 95% CI 1.39 –1.61). Mortality risks for IHD and CVA were increased by 59% and 52%, respectively (meta-SMR 1.59, 95% CI 1.46 –1.73 and meta-SMR 1.52, 95% CI 1.40 –1.67, respectively). We identified asymmetry in the funnel plot (Egger’s test P 0.002), as well as significant heterogeneity in all main analyses (P < 0.0001). Subgroup analyses showed that inception cohort studies (n 4, comprising 2,175 RA cases) were the only group that did not show a significantly increased risk for CVD (meta-SMR 1.19, 95% CI 0.86 –1.68). Conclusion. Published data

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