Making an impact on mortality in rheumatoid arthritis: targeting cardiovascular comorbidity.

Since the first report in 1953 (1), several studies have confirmed the observation of excess mortality rates in various rheumatoid arthritis (RA) prevalence and incidence cohorts. On review, there appears to be little doubt that people with RA have a lower life expectancy (2–4). These reports, along with data from observational studies demonstrating that most patients eventually experience severe functional decline (5), work disability (6), and joint destruction (7), have led to considerable changes in treatment strategies. Rheumatologists have abandoned the traditional pyramid paradigm (“go low; go slow”) and are treating their patients earlier and more aggressively (8). Introduction of new diseasemodifying antirheumatic drugs (DMARDs), more aggressive use of “old” drugs both singly and in combination, as well as reintroduction of corticosteroids in the treatment of early disease have fundamentally changed the approach to treating patients with RA (9). Along with the therapeutic changes, there have been important advances in the standardization and adoption of outcome measures of disease activity, severity, and quality of life (10). Fortunately, these measures are now widely used in almost all trials and observational studies, and we know that therapeutic changes have been successful in improving the quality of life and functioning of RA patients. These changes in the approach to RA have led to improved morbidity rates, but evidence of improved mortality rates in RA remains relatively scant. For instance, recent cohort studies have documented similar mortality rates in patients with RA and the general population (11,12), and improved survival associated with response to methotrexate has been reported, but from only 2 treatment centers, albeit with important databases (13,14). Other studies, however, concluded that survival in RA has not improved in recent decades (15,16), and one study suggested increased mortality in methotrexate-treated RA patients who have cardiovascular disease (17). Several explanations have been offered for these conflicting signals. First, apparent improvement in survival in certain studies could be due to the more frequent use of population-based cohorts rather than clinic-based or referral cohorts in recent years (18,19). Second, since the excess mortality in RA does not become apparent until approximately 8–10 years after disease onset, inception cohorts followed too briefly will fail to capture this excess, and any improvement in mortality rates can only be identified after a long lag time (16,19). Furthermore, there may be hidden problems in retrospective cohort studies that could potentially bias the results (20). Finally, traditional measures of RA disease activity may not necessarily be the best predictors of mortality. This commentary suggests an additional explanation that rheumatologists should be able to address in the clinic: the undertreatment of—mostly cardiovascular— comorbidity. In very recent work, Navarro-Cano et al (21) confirmed the independent contributions of RA and comorbidity to mortality. Most of this contribution comes from the widespread cardiovascular comorbidity (22). Perhaps excess mortality in RA is primarily linked to etiologies such as the effects of systemic inflammation on vascular integrity (23), and the treatments, although Maarten Boers, MSc, MD, PhD, Ben Dijkmans, MD, PhD: VU University Medical Center, Amsterdam, The Netherlands; Sherine Gabriel, MD, MSc, Hilal Maradit-Kremers, MD, MSc: Mayo Clinic, Rochester, Minnesota; James O’Dell, MD: University of Nebraska Medical Center, Omaha; Theodore Pincus, MD: Vanderbilt University Medical Center, Nashville, Tennessee. Address correspondence and reprint requests to Maarten Boers, MSc, MD, PhD, Professor of Clinical Epidemiology, Department of Clinical Epidemiology and Biostatistics, 9B-116, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: keb.info@vumc.nl. Submitted for publication October 23, 2003; accepted in revised form February 28, 2004.