Two recent studies of patients with rheumatoid arthritis (RA) have sent up a red flag for physicians caring for veterans with the disease; such patients appear to be at increased risk for cardiovascular disease due to inflammation and several other risk factors.

One study, published in the journal Arthritis Research & Therapy, indicates that RA sufferers are at an increased risk of dying due to cardiovascular disease. The second study, published in General Hospital Psychiatry, is based on patients drawn from VA national administrative and pharmacy databases and shows that depressed patients with RA are at greater risk for myocardial infarction (MI).

“These two studies, especially the one from the VA database, emphasized once more that the VA clinical database is an immense source of information – and this study in particular is testament to the strength of that database,” says Subhash Banerjee, MD, FACC, FSCAI, chief, Division of Cardiology, and co-director of the Cardiac Catheterization Laboratory in the VA North Texas Health Care System in Dallas and associate professor of medicine at the University of Texas Southwestern Medical Center in Dallas.

The database, he notes, also was used in a study in 2008 that addressed the strong association of men with RA and their cardiovascular events. “The question begs to be asked, what is it that makes these patients so susceptible to adverse cardiovascular outcomes?” Banerjee poses.

Andreas Reimold, MD, chief of the Rheumatology Section at the Dallas VA Medical Center, assistant professor of medicine at the University of Texas Southwestern Medical Center and co-author of the 2008 paper, says that it has been recognized for a while that the risk of MI — and certainly heart failure – are greater in patients with RA. “The interesting part about this is that it’s not just a traditional cardiovascular risk factor – family history, cholesterol and so on; it appears to be something additional,” Reimold says.

The main factor that is speculated in the literature, he adds, is the inflammatory state itself.

“When you have RA, your inflammation is elevated for long periods of time,” he notes, adding that inflammation occurs throughout the body – not just, for example, where the greatest discomfort is felt. The best speculation, he says, is that this adds to more plaques and more instability in coronary arteries.

RA and atherosclerosis are both chronic inflammatory disease states, notes Banerjee; the specific cells involved in the inflammatory process are very much alike —  and so are the drivers. “The inflammatory markers are cytokines —  especially interleukins that are responsible for driving and perpetuating these inflammatory cascades, and are very much alike for RA and for the development and rupture of atherosclerotic plaque, which is ultimately responsible for cardiac events,” he explains.

It’s very important, he continues, to recognize that it is the inflammatory patho-physiology of the arthritic process that relates to heightened risk. “Non-inflammatory arthritis conditions may be less related,” he declares.

Clearly, this is not the whole story, adds Liron Caplan, MD, PhD, staff physician, Denver Veterans Affairs Medical Center, assistant professor of medicine/rheumatology, University of Colorado School of Medicine, and co-author of the General Hospital Psychiatry paper on veterans with depression.

“While cardiovascular risk factors have been traditionally associated with heart attacks and have been identified more commonly with folks with RA and similar inflammatory conditions, it does not appear to entirely explain the increase in heart attacks, so there are non-traditional factors that are presumed to increase this risk and are a very active area of inquiry,” he says. In some cases, he notes, researchers are looking for a specific biomarker that might include a different patho-physiological pathway, while “Others might be behavioral, such as depression.”