Rheumatoid Arthritis and Mortality Among Women During 36 Years of Prospective Follow-Up: Results From the Nurses' Health Study

Abstract

Objective: To evaluate rheumatoid arthritis (RA) and mortality risk among women followed prospectively in the Nurses' Health Study (NHS).

Methods: We analyzed 119,209 women in the NHS who reported no connective tissue disease at enrollment in 1976. Comorbidity and lifestyle data were collected through biennial questionnaires. Incident RA cases were validated by medical records review. Cause of death was determined by death certificate and medical records review. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause, cardiovascular disease (CVD), cancer, and respiratory disease mortality for women with RA compared to those without RA.

Results: We validated 964 incident RA cases and identified 28,808 deaths during 36 years of prospective follow-up. Of 307 deaths among women with RA, 80 (26%) were from cancer, 70 (23%) were from CVD, and 44 (14%) were from respiratory causes. Women with RA had increased total mortality (HR 1.40, 95% CI 1.25-1.57) compared to those without RA, independent of mortality risk factors, including smoking. RA was associated with significantly increased respiratory disease mortality (HR 2.06, 95% CI 1.51-2.80) and cardiovascular disease mortality (HR 1.45, 95% CI 1.14-1.83), but not cancer mortality (HR 0.93, 95% CI 0.74-1.15). For women with seropositive RA, respiratory disease mortality was nearly 3-fold higher than among non-RA women (HR 2.67, 95% CI 1.89-3.77).

Conclusion: Women with RA had significantly increased mortality compared to those without RA. Respiratory disease and cardiovascular disease mortality were both significantly elevated for women with RA. The nearly 3-fold increased relative risk of respiratory disease mortality was observed only for those with seropositive RA.

Figure 1

Standardized mortality rates during 36 years of follow-up in the Nurses’ Health Study (NHS) for women with all rheumatoid arthritis (RA; all-RA), seropositive RA (sero + RA), seronegative RA (sero– RA), and no RA (non-RA). Mortality rates were standardized to the age-specific US female population mortality rate by calendar year. There were too few deaths among women with RA diagnosed in the first 16 years of NHS follow-up to provide stable estimates of mortality rates during this period. py = person-years.

Figure 2

Kaplan-Meier curves for survival after incident rheumatoid arthritis (RA) diagnosis and age- and period-matched controls at index date of RA diagnosis for women in the Nurses’ Health Study comparing (A) all RA and controls (P < 0.001 by log rank test), (B) seropositive RA and controls (P < 0.001 by log rank test), and (C) seronegative RA and controls (P = 0.066 by log rank test).