Women with rheumatoid arthritis (RA) had a 40% greater risk for mortality than women without RA during 36 years of follow-up in a longitudinal cohort study (Sparks JA, et al. Arthritis Care Res (Hoboken). 2016;68:753-762).
The higher all-cause mortality in women with RA was driven primarily by cardiovascular and respiratory disease, including an approximately 3-fold greater risk for respiratory mortality in women with seropositive RA. Cancer-related mortality did not differ between women with and without RA.
Several previous studies have suggested that patients with RA have an increased mortality risk compared with the general population, a disparity that has persisted despite the emergence of disease-modifying antirheumatic drugs. However, most of the earlier studies compared data from RA-only populations with age- and sex-standardized mortality estimates derived from the population at large.
Cause-specific mortality had not been assessed previously in cohorts including individuals with and without RA. Using data from the Nurses’ Health Study (NHS), Jeffrey A. Sparks, MD, an instructor in medicine at Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, and colleagues sought to determine whether RA was associated with increased mortality, including all-cause, cardiovascular, respiratory, and cancer, compared with NHS participants who did not have RA.
The analysis comprised approximately 120,000 women nurses with a mean age of 42 years at enrollment; follow-up was from 1976 to 2012. The investigators identified 964 diagnoses of RA. Baseline characteristics did not differ significantly between participants with and without the disease.
During follow-up, 307 (31.8%) patients in the RA group died compared with 28,501 (24.1%) participants without RA. Women in the RA group had a significantly higher total mortality after adjustment for age, income, period, smoking pack-years, body mass index, menopausal status and hormone use, and physical activity (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.25-1.57).
Women with seropositive RA accounted for most of the mortality difference, reflected in an HR of 1.51 versus NHS participants without RA. In contrast, women with seronegative RA had an adjusted mortality of 1.15 versus participants without RA (95% CI, 0.95-1.39).
By a Kaplan-Meier analysis, women with RA had significantly worse overall survival after the date of RA diagnosis (P <.001) compared with age- and sex-matched controls in the non-RA group. In addition, study participants with seropositive RA had significantly worse survival after RA diagnosis (P <.001) than their seronegative counterparts (P = .066).
The most common causes of death in the RA group were cancer (26.1%), cardiovascular disease (22.8%), and respiratory disease (14.3%). Dr Sparks and colleagues noted that RA was cited as the cause of death in 8.8% of cases. In the non-RA group, the most common causes of death were cancer (40.6%), cardiovascular disease (21.8%), other (8.5%), respiratory disease (7.2%), and dementia (7.0%).
Analysis of cause-specific mortality showed that patients in the RA group had an approximately 2-fold greater risk for respiratory mortality than NHS participants without RA (HR, 2.06; 95% CI, 1.15-2.80). The HR increased to 2.67 for women with seropositive RA (95% CI, 1.89-3.77). Respiratory mortality did not differ significantly between women with seronegative RA and those in the non-RA group (HR, 0.98; 95% CI, 0.49-1.99).
Women with RA had a 45% increased risk for cardiovascular mortality compared with the non-RA group (HR, 1.45; 95% CI, 1.14-1.83). Women with seropositive RA and seronegative RA had identical HRs of 1.41, although the difference from the non-RA group achieved statistical significance only for the women with seropositive RA (95% CI, 1.03-1.93; 95% CI, 0.98-2.02 for women with seronegative RA).
Cancer-associated mortality did not differ significantly between NHS participants with and without RA (HR, 0.93; 95% CI, 0.74-1.15). Similar results emerged from an analysis of the seropositive and seronegative RA subgroups.
“Clinicians should be aware of the increased mortality risk among RA patients, particularly respiratory disease−related mortality in seropositive RA,” Dr Sparks and colleagues concluded. “Further research is warranted to determine factors that may reduce the excess mortality in RA, particularly from cardiovascular and respiratory causes.”