Systemic inflammation and other activity around rheumatoid arthritis may lead to the progression of atherosclerosis in people with RA, claims new data.
This study presented at the American College of Rheumatology Annual Scientific Meeting in Atlanta also show that this progression may be modified favorably by TNF inhibitors and detrimentally by glucocorticoids.
"These data suggest that by limiting inflammation in RA patients, you can potentially limit the rapidity of accumulation of-at least-carotid atherosclerosis, which is what our study looked at," says Jon T. Giles, MD, MPH; assistant professor of medicine in the Division of Rheumatology at Johns Hopkins and lead investigator in the study. "And because carotid atherosclerosis tends to be correlated with coronary atherosclerosis, then potentially you would have fewer cardiovascular events like myocardial infarction and stroke in RA patients. These links with subclinical atherosclerosis make intuitive sense, but they haven''t [previously] been shown in prospective studies."
Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts 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.
Coronary and extra-coronary atherosclerosis-the buildup of plaque in the artery walls-are increased in people with RA, when compared to people without the disease. However, few studies have explored predictors of change in atherosclerosis in RA patients. In a study funded in part by the ACR Research and Education Foundation, researchers recently addressed this by following 158 people with RA who were already enrolled in a study of cardiovascular disease in RA.
They focused on monitoring intima-medial thickness - the thickness of artery walls that is used in diagnosing atherosclerosis. Participants underwent an ultrasound of their common and internal carotid arteries (arteries that provide blood to the head and neck) at the first and third study visits, which were an average of 3.2 years apart. Through this, researchers found that the thickness of the common carotid artery walls increased over time in 82 percent of the participants and the thickness in the internal carotid artery walls increased in 70 percent of the participants.
When the researchers adjusted their data to consider demographics, cardiovascular risk factors, and the thickness of the carotid artery walls at the beginning of the study, they found that those participants who used anti-TNF treatment at the beginning of the study had a 37 percent lower rate of progression of the thickness of the common carotid artery walls than those who did not use anti-TNF treatment. They also noted that the adjusted average yearly change in the thickness of the common carotid artery walls was significantly higher for patients earlier in their RA when compared to those who had the disease longer.
When looking at thickness in the internal carotid artery walls, prednisone exposure was the only RA feature researchers associated with progression of atherosclerosis after adjusting the data to consider demographics, cardiovascular risk factors and thickness of the internal carotid artery walls at the beginning of the study. And, this rate was significantly lower in participants who were prescribed statins at the beginning of the study.
"There seem to be some medications used in RA that can either be protective or can promote atherosclerosis," Dr. Giles says. "Prednisone may be more associated with progression of atherosclerosis in some vascular beds, but medications like TNF inhibitors and statins that are taken to lower cholesterol may limit atherosclerosis in these patients."
Finally, researchers noted that those participants with a higher than average number of swollen joints and a higher than average c-reactive protein were independently and significantly associated with incidence of plaque.
The next step for researchers is to conduct interventional studies that randomize patients to receive one medication or another and determine the direct cause-and-effect relationship between the medications and the progression of atherosclerosis, either in coronary artery circulation or the carotid artery circulation.
"Those studies are in the planning stages," Dr. Giles says. "They are big studies and hard to organize, but they''re really required to determine what the role of the medications are in terms of protection."