Autoantibodies Could Be a Warning Sign for Cardiovascular Disease in People with Rheumatoid Arthritis

Newswise — WASHINGTON – The presence of autoantibodies in the blood may be connected to a higher risk of the development of cardiovascular disease, not just in individuals with diagnosed autoimmune diseases like rheumatoid arthritis, but in the general population, according to new research findings presented this week at the American College of Rheumatology Annual Meeting in Washington, D.C.

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.

The American College of Rheumatology is an international professional medical society that represents more than 9,000 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 www.acrannualmeeting.org or join the conversation on Twitter by using the official hashtag: #ACR2012.

Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care. Also, discover the ACR’s Simple Tasks campaign, which highlights the severity of rheumatic diseases and the importance of early and appropriate referral to a rheumatologist.

Editor’s Note: Darcy Majka, MD, MS will present this research during the ACR Annual Meeting at the Walter E. Washington Convention Center at 4:30 PM on Monday, November 12 in Ballroom B. Dr. Majka will be available for media questions and briefing at 8:30 AM on Tuesday, November 13 in the on-site press conference room, Room 203 A-B.

Presentation Number: 1664

Autoantibodies Are Associated with Subclinical Atherosclerosis and Cardiovascular Endpoints in Caucasian and African American Women in a Prospective Study: the Multi-Ethnic Study of Atherosclerosis (MESA)

Darcy S. Majka (Northwestern University, Chicago, Ill.)Rowland W. Chang (Northwestern University, Chicago, Ill.)Richard M. Pope (Northwestern University Medical School, Chicago, Ill.)Marius C. Teodorescu (TheraTest Laboratories Inc., Lombard, Ill.)Elizabeth W. Karlson (Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.)Thanh Huyen T. Vu (Northwestern University, Feinberg School of Medicine, Chicago, Ill.)Joseph Kang (Northwestern University, Feinberg School of Medicine, Chicago, Ill.)Kiang Liu (Northwestern University, Chicago, Ill.)

Background/Purpose: Although the association between rheumatoid arthritis (RA) and cardiovascular disease (CVD) is established, the exact mechanism is not known. Subjects who later develop RA were shown to have increased risk of myocardial infarction (MI) in the preclinical period prior to RA symptoms indicating that autoimmunity might be a risk factor for CVD. Therefore, we tested the hypothesis that RA-related autoantibodies are independent risk factors for subclinical atherosclerosis and subsequent clinical CVD events.

Methods: MESA is a multicenter population based study cohort prospectively collecting CVD outcome and risk factor data in 6814 middle-aged to elderly multi-ethnic participants since 2000. At MESA baseline, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP-2) by ELISA and coronary artery calcium (CAC) by CT were measured in 6557 AA, Caucasian, Hispanic and Chinese participants who were then followed for 7.1 years for coronary heart disease (CHD) Hard endpoints (MI, resuscitated cardiac arrest, CHD death) and CVD Hard endpoints (MI, cardiac arrest, CHD death, stroke, stroke death). We assessed the associations between baseline RF/anti-CCP and CAC stratified by race/gender using logistic regression adjusting for traditional CVD risk factors. We used Cox regression to determine race/gender-specific associations between RF/anti-CCP and clinical CVD endpoints.

Results: 12.2% had CAC >=300; After 7.1 years, 3.0% had Hard CHD endpoints; 4.8% had Hard CVD endpoints. RF IgM, RF IgA and anti-CCP were positive in 15.9%, 8.7%, and 2.0%, respectively. 4.0% were positive for both and 20.6% were positive for either RF isotype. RA-related autoantibody positivity varied with race and was highest in AA’s (RF: p<0.001, anti-CCP: p<0.003). RF and anti-CCP were associated with CAC in Caucasian and AA women after adjustment for traditional risk factors (Table 1). Table 2 demonstrates strong associations between RA-related autoantibodies and clinical CVD events in AA women. There were no clear associations in Hispanic and Chinese participants.

Conclusion: This study demonstrates that RA-related autoantibodies are associated with subclinical and clinical atherosclerosis in a population based cohort. These findings indicate autoimmune factors may play a role in the pathogenesis of atherosclerosis, even in individuals without RA.