Higher mortality in postmenopausal women with RA and anti-CCP antibodies

New research shows mortality rates are two times higher in postmenopausal women with rheumatoid arthritis (RA) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Findings published in the American College of Rheumatology (ACR) journal Arthritis & Rheumatism, soon to be called Arthritis & Rheumatology, indicate the higher mortality rates persisted after adjusting for age, positive rheumatoid factor, positive antinuclear antibodies (ANA) and disease modifying anti-rheumatic drug (DMARD) use.

According to the ACR, RA affects 1.3 million adults in the U.S. with 75% of those being women. Previous studies report that RA patients have mortality rates 1.5-fold higher than healthy controls. Medical evidence suggests that excess mortality is mainly caused by cardiovascular disease and is greater in groups with existing RA compared to those newly diagnosed.

However, observational data indicate that methotrexate may reduce cardiovascular disease and mortality.

For the present study researchers from the University of Pittsburgh, led by Drs. Lewis Kuller and Larry Moreland, measured anti-CCP, rheumatoid factor and ANA in close to 10,000 women who self-reported RA as part of the Women's Health Initiative (WHI)—clinical trials and observational study of postmenopausal women, conducted by the National Institutes of Health (NIH). Participants included in the present research had a mean age of 64 years with 65% white, 25% black and 10% Hispanic.

Results show that anti-CCP was prevalent in 8.1% of the group, of whom 58% reported DMARD use during follow-up. Only 7.3% of the remaining 9,179 women with self-report RA, but negative anti-CCP, were using DMARDs. During the 10-year study period, 13% of women died—14% who self-reported RA at the start of the study and follow-up; 16% who reported RA at baseline; and 11% who reported RA at follow-up.

Further analysis determined that cardiovascular disease, including coronary heart disease and stroke, and cancer were the main cause of death among women with RA. Women with positive anti-CCP had a substantially higher mortality risk that was independent of DMARD use, including methotrexate, and modifiable risk factors (obesity, smoking) associated with mortality.

"Our study is the first large longitudinal study to evaluate anti-CCP, RF, risk factors and mortality," said Dr. Kuller. "Further investigation to determine specific causes of excess mortality, particularly among RA patients with positive anti-CCP, are needed."