Rheumatoid arthritis linked to increased risk of death

Boston, MA– Rheumatoid arthritis (RA) has been associated with increased risk of death in the past, but a new study by investigators from Brigham and Women's Hospital (BWH) brings that risk into sharper focus. Using data from the Nurses' Health Study, which has followed more than 100,000 female registered nurses since 1976, researchers found that rheumatoid arthritis significantly increased participants' overall risk of death, especially risk of death due to respiratory or cardiovascular causes. The new work suggests the importance of vigilance in monitoring respiratory and cardiovascular symptoms among patients with RA, particularly those who are seropositive.

"Previous studies have suggested that RA may be associated with increased mortality, but were not able to control for other variables, such as smoking, that affect both RA and mortality risks," said corresponding author Jeffrey Sparks, MD, MMSc, a physician in BWH's Division of Rheumatology, Immunology and Allergy. "Because the Nurses' Health Study is so large and has been following participants for so long, we were able to gather much more information about our subjects – we could follow them before and after diagnosis, take their health behaviors into account and determine specific causes of death. By doing so, we found strong evidence of increased risk for respiratory, cardiovascular and overall mortality for patients with RA."

Sparks and his colleagues evaluated 964 women in the Nurses' Health Study with RA and compared their mortality rates to women in the study without RA. The team controlled for other risk factors, including smoking, a known cause of worse respiratory and cardiovascular mortality, as well as age, body mass index, physical activity and diet among others. They found that RA was associated with a 40 percent increased risk of death. The research team followed up on each RA case where participants had died of respiratory causes. They found that many patients with RA died of chronic obstructive pulmonary disease (COPD).

"We finely adjusted for smoking in our analyses so what we're seeing appears to be due to something else," said Sparks.

The researchers then evaluated deaths from cancer, cardiovascular and respiratory causes. They found that RA was significantly associated with both cardiovascular and respiratory mortality, but not cancer mortality. The researchers also looked at differences between the two types of RA, "seropositive" and "seronegative." Patients with seropositive RA have auto-antibodies related to RA, and generally have more severe symptoms. The team found that participants with seropositive RA were at nearly three-fold increased risk of respiratory mortality compared to their counterparts who did not have RA. Seronegative RA, on the other hand, was not significantly associated with increased risk of respiratory mortality.

"We found that whether participants with RA were seropositive or seronegative really mattered – those who were seropositive were at higher risk, particularly for respiratory mortality," said Sparks.

Sparks notes that although most clinicians are aware of elevated cardiovascular disease risk among RA patients, the new study suggests the importance of monitoring respiratory symptoms, even among patients who are not smokers or have given up smoking.

"We hope that this study will encourage patients and clinicians to be more aware that patients with RA are at increased risk of both respiratory and cardiovascular mortality, particularly patients with seropositive RA," said Sparks.

Preclinical studies have also suggested a connection between the lungs and RA. Before patients present with joint pain and the classic symptoms of RA, some will present to clinic with anatomical lesions in their lungs without joint findings. Sparks and his colleagues are interested in better understanding how RA develops and if certain preclinical factors may help predict risk of RA and subsequent clinical outcomes, with the goal of improving screening and prevention.

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Other researchers who contributed to this work include Shun-Chiao Chang, Katherine P. Liao, Bing Lu, Alexander R. Fine, Daniel H. Solomon, Karen H. Costenbader and Elizabeth W. Karlson.

This work was supported by the National Institutes of Health (grants CA087969, CA049449, CA050385, and CA067262), the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (AR049880, AR052403, AR047782, AR061362 and AR059073) the Rheumatology Research Foundation Scientist Development Award, the National Institutes of Health Loan Repayment Award (L30 AR066953), Harvard Catalyst, The Harvard Clinical and Translational Science Center, National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award (1UL1 TR001102-01) and Harvard University and its affiliated academic health care centers. The funders had no role in study design, data collection, analysis, decision to publish, or preparation of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University, its affiliated academic health care centers, or the National Institutes of Health.

Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 4.2 million annual patient visits, nearly 46,000 inpatient stays and employs nearly 16,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Brigham Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $600 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH continually pushes the boundaries of medicine, including building on its legacy in transplantation by performing a partial face transplant in 2009 and the nation's first full face transplant in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative as well as the TIMI Study Group, one of the premier cardiovascular clinical trials groups. For more information, resources and to follow us on social media, please visit BWH's online newsroom.