Women with Rheumatoid Arthritis Have Significantly Higher Risk of Mortality

Newswise — BOSTON — Women with rheumatoid arthritis are at significantly higher risk of all-cause mortality, particularly respiratory causes, compared to women without the disease, according to new research findings presented this week at the American College of Rheumatology Annual Meeting in Boston.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

Using data from the Nurses’ Health Study conducted on 121,700 women gathered from 1976 to 2012, researchers at Brigham and Women’s Hospital and Harvard Medical School in Boston validated 964 incident RA cases and identified 28,808 deaths in the entire cohort with 36 years of follow-up. Of the 307 deaths among women with RA, 26 percent were from cancer, 23 percent from cardiovascular disease, and 16 percent from respiratory causes. In contrast, women without RA died from the following causes: 41 percent from cancer, 22 percent from cardiovascular disease, and 7 percent from respiratory causes.

Compared to women without RA, the researchers determined that women with RA had 40 percent increased mortality from all causes, after adjusting for age and other mortality risk factors. This was likely driven by cardiovascular and respiratory causes, but cancer did not appear to be increased. Women with seropositive RA had significantly 51 percent higher risk of death compared to women without RA, whereas the mortality risk in seronegative RA was not statistically different from non-RA women.

“We aimed to study deaths and causes of death in a cohort in which women have been followed very closely before and after development of RA and directly compared to women without RA. All the participants in this study had repeated assessment of behavioral factors, such as cigarette smoking, comorbid diseases such as cardiovascular disease, and other mortality risk factors, enabling us to study the independent effect of having RA on the risk of death,” said Dr. Jeffrey Sparks, from Brigham and Women’s Hospital in Boston and a lead author of the study. In the study, the researchers found that each five years of having RA increased the women’s mortality by 11 percent compared to women without the disease. Women with seropositive RA had almost three times the respiratory mortality risk compared to women without RA, but women with seronegative RA had no such increased risk. For women with RA, respiratory deaths were due to chronic obstructive pulmonary disease, pneumonia, chronic interstitial lung disease, asthma and other respiratory diseases.

The researchers concluded that women diagnosed with RA have a 1.4 fold increased risk of death from any cause compared to women without RA. Death from respiratory causes appears to be an important but understudied cause of death in RA patients, especially in seropositive RA patients. The study provided evidence of high RA mortality risks that are unexplained by traditional factors such as cigarette smoking.

“This study highlights the clinical necessity of recognizing and addressing complications of RA, such as respiratory disease and cardiovascular disease, which associated with early mortality,” Dr. Sparks said.

Funding sources for this study included the National Institutes of Health and the Rheumatology Research Foundation.

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The American College of Rheumatology is an international professional medical society that represents more than 9,500 rheumatologists and rheumatology health professionals around the world. Its mission is to Advance Rheumatology! The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. For more information about the meeting, visit http://www.acrannualmeeting.org/ or join the conversation on Twitter by using the official #ACR14 hashtag.

Paper Number: 818

Incident Rheumatoid Arthritis and Risk of Mortality Among Women Followed Prospectively from 1976 to 2010 in the Nurses’ Health Study

Jeffrey A. Sparks, Shun-Chiao Chang, Katherine P. Liao, Bing Lu, Daniel H. Solomon, Karen H. Costenbader and Elizabeth W. Karlson, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

Background/Purpose RA has been associated with increased mortality compared to general population estimates. Previous studies were limited due to the inability to directly compare RA patients to controls, short follow-up, and lack of detailed data on clinical, lifestyle, and serologic factors. We evaluated mortality among women followed prospectively prior to RA diagnosis, directly comparing to women without RA.

Methods We conducted a study of RA and mortality among 121,700 women followed from 1976 to 2010 in the Nurses’ Health Study (NHS). Incident RA was validated by medical record review according to the 1987 ACR RA criteria and classified by serostatus. Women who reported RA or other connective tissue diseases before the start of NHS were excluded. Women were followed from cohort entry to death or end of follow-up and were censored for loss to follow-up. Deaths were validated by the National Death Index; death certificate and medical record review determined cause of death. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease (CVD), cancer, and respiratory mortality for women with RA compared to women without RA. We obtained HRs for mortality by RA duration and serologic RA phenotype. Models were adjusted for age, demographics and other mortality factors, including physical activity, smoking, obesity, comorbidities, and family history of cancer, CVD, and diabetes.

Results We validated 960 incident RA cases and identified 25,699 deaths in 34 years of NHS follow-up. Of the 261 deaths among women with RA, 75 (29%) were from cancer, 58 (22%) were from CVD, and 43 (16%) were from respiratory causes. Compared to women without RA, women with RA had increased all-cause mortality that remained significant after adjusting for age and other mortality factors (HR 2.07, 95% CI 1.83-2.35, Table). Mortality was significantly increased for seropositive (HR 2.33, 95% CI 2.00-2.71) and seronegative RA (HR 1.60, 95% CI 1.30-1.98) compared to non-RA women. Each five years of RA duration conferred a 32% (95% CI 27-36%) increased mortality compared to non-RA. Women with RA had significantly increased risk for mortality from CVD (HR 1.87, 95% CI 1.44-2.43), cancer (HR 1.35, 95% CI 1.07-1.69) and respiratory (HR 4.50, 95% CI 3.28-6.17) causes compared to women without RA. Respiratory mortality for women with seropositive RA was six-fold higher than non-RA women (HR 6.23, 95% CI 4.38-8.85).

Conclusion In 34 years of prospective follow-up, women diagnosed with RA had a two-fold increased risk of death from any cause compared to women without RA. Respiratory mortality was six-fold higher in seropositive RA and women with RA were significantly more likely to die from CVD and cancer than women without RA. Respiratory mortality appears to be an important but understudied cause of death in RA. These findings provide evidence of high RA mortality burden that is unexplained by traditional mortality predictors.

Disclosures: J. A. Sparks, None.S. C. Chang, None.K. P. Liao, None.B. Lu, None.D. H. Solomon, None.K. H. Costenbader, None.E. W. Karlson, None.