Autoantibodies could be a warning sign for cardiovascular disease in people with rheumatoid arthritis

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, limitation of motion and loss of function of multiple joints. Though joints are the principal areas 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.

Researchers based at Northwestern University Feinberg School of Medicine in Chicago, Ill., looked at the possible connections between the presence of autoantibodies in people with RA and their higher risk of developing cardiovascular disease. Although scientists have established the higher prevalence of cardiovascular disease in people with RA, the exact mechanism is still unknown, says Darcy S. Majka, MD, lead investigator of the study and assistant professor of medicine and preventive medicine at Northwestern.

"There are still a lot of mysteries as to the etiology of the increased risk of cardiovascular disease in rheumatoid arthritis," says Dr. Majka. "We also know that individuals with rheumatoid arthritis have detectable autoantibodies in their blood prior to the onset of rheumatoid arthritis symptoms. This indicates that the autoimmune process starts before the symptoms of rheumatoid arthritis occur."

Dr. Majka and her colleagues sought to learn more about the connections between autoimmunity, defined in this study by the presence of autoantibodies, and the risk of cardiovascular disease. They examined data collected in the Multi-Ethnic Study of Atherosclerosis, a multi-center (called MESA), population-based study of cardiovascular disease risk factor and outcomes in more than 6,800 people of various racial and ethnic backgrounds. In MESA, levels of the RA-related autoantibodies rheumatoid factor and anti-cyclic citrullinated peptide were measured in the stored serum of 6,557 MESA participants who also had coronary artery calcium measured by CT scanning. These participants were followed by the MESA study for an average of 7.1 years to track their development of coronary heart disease or cardiovascular disease events like heart attacks.

Findings showed that at baseline 12.2 percent of the MESA study participants had coronary artery calcium levels greater than or equal to 300. In addition, after 7.1 years, 3 percent developed serious coronary heart disease outcomes like myocardial infarction, resuscitated cardiac arrest or even death due to coronary heart disease. When stroke or death from stroke were taken into account along with coronary heart disease, 4.8 percent of the MESA participants had events.

Having a positive rheumatoid factor or anti-CCP-2 was associated with twice the odds of having a high coronary artery calcium score in both African-American and Caucasian women. African-American women with positive autoantibodies also had greater than twice the risk of having clinical cardiovascular disease events. There were no associations between autoantibody production and coronary artery score or clinical CVD events in Hispanics or Chinese participants. It is still unclear why these disparities exist, Dr. Majka says.

By analyzing data from such a large, comprehensive population, the researchers believe they taken a significant step in better understanding how autoimmunity may be involved in the development of cardiovascular disease in both individuals with RA and even in the general population.

"This study indicates that autoimmunity might be associated with both clinical and subclinical atherosclerosis in the general population," Dr. Majka concludes. "While it would be far too premature to suggest that we should be checking for RA-related autoantibodies in everyone, they might be one potential novel biomarker for cardiovascular disease development."

Funding sources for this study included the National Heart, Lung and Blood Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and National Institute of Allergy and Infectious Diseases all part of the National Institutes of Health; and the Arthritis Foundation Arthritis Investigator Award.