Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies

Arthritis Rheum. 2008 Dec 15;59(12):1690-7. doi: 10.1002/art.24092.


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 I(2) 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 indicate that CVD mortality is increased by approximately 50% in RA patients compared with the general population. However, we found that study characteristics may influence the estimate.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / complications*
  • Cardiovascular Diseases / mortality*
  • Confidence Intervals
  • Humans
  • Myocardial Ischemia / mortality
  • Stroke / mortality