Mortality Trends in Rheumatoid Arthritis: The Role of Rheumatoid Factor

ANGEL GONZALEZ; MURAT ICEN; HILAL MARADIT KREMERS; CYNTHIA S. CROWSON; JOHN M. DAVIS; TERRY M. THERNEAU; VERONIQUE L. ROGER; SHERINE E. GABRIEL

Abstract

Objective

We previously demonstrated a widening in the mortality gap between subjects with rheumatoid arthritis (RA) and the general population. We examined the contribution of rheumatoid factor (RF) positivity on overall mortality trends and cause-specific mortality.

Methods

A population-based RA incidence cohort (1955–1995, and aged ≥18 yrs) was followed longitudinally until death or January 1, 2006. The underlying cause of death as coded from national mortality statistics and grouped according to ICD-9/10 chapters was used to define cause-specific mortality. Expected cause-specific mortality rates were estimated by applying the age-, sex-, and calendar-year-specific mortality rates from the general population to the RA cohort. Poisson regression was used to model the observed overall and cause-specific mortality rates according to RF status, accounting for age, sex, disease duration, and calendar year.

Results

A cohort of 603 subjects (73% female; mean age 58 yrs) with RA was followed for a mean of 16 years, during which 398 died. Estimated survival at 30 years after RA incidence was 26.0% in RF+ RA subjects compared to 36.0% expected (p < 0.001), while in RF– RA subjects, estimated survival was 29.1% compared to 28.3% expected (p = 0.9). The difference between the observed and the expected mortality in the RF+ RA subjects increased over time, resulting in a widening of the mortality gap, while among RF– RA subjects, observed mortality was very similar to the expected mortality over the entire time period. Among RF+ RA subjects, cause-specific mortality was higher than expected for cardiovascular [relative risk (RR) 1.50; 95% confidence interval (CI) 1.22, 1.83] and respiratory diseases [RR 3.49; 95% CI 2.51, 4.72]. Among RF– RA subjects, no significant differences were found between observed and expected cause-specific mortality.

Conclusion

The widening in the mortality gap between RA subjects and the general population is confined to RF+ RA subjects and largely driven by cardiovascular and respiratory deaths.

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Footnotes

A. Gonzalez, MD, Department of Internal Medicine, Caritas St. Elizabeth’s Medical Center; M. Icen, MD; H. Maradit Kremers, MD, MSc, Division of Epidemiology, Department of Health Sciences Research; C.S. Crowson, MS, Division of Biostatistics, Department of Health Sciences Research; J.M. Davis III, MD, Division of Rheumatology, Department of Medicine; T.M. Therneau, PhD, Division Biostatistics, Department of Health Sciences Research; V.L. Roger, MD, MPH, Division of Epidemiology, Department of Health Sciences Research, and Division of Cardiovascular Diseases, Department of Medicine; S.E. Gabriel, MD, MSc, Professor, Division of Epidemiology, Chair, Department of Health Sciences Research, and Division of Rheumatology, Department of Medicine, Mayo Clinic.
Supported in part by a grant from the US National Institutes of Health, NIAMS (R01 AR46849), and the National Institutes of Health (AR-30582) US Public Health Service.
- Accepted for publication January 4, 2008.