- More than 1.3 million adults in the United States are affected by rheumatoid arthritis (RA), a chronic autoimmune disease that causes inflammation and swelling in the joints.
- Research suggests that inflammation can cause atherosclerosis and may contribute to heart disease, which may explain the higher incidence of heart disease among individuals with RA.
- According to a recent study, medications commonly prescribed to alleviate joint inflammation in RA also appear to decrease the likelihood of developing cardiovascular disease.
A new study, completed by researchers at Columbia University in New York and Brigham and Women’s Hospital in Boston, suggests that some drugs used to treat rheumatoid arthritis (RA) may also help decrease the risk of heart disease.
The research involved 115 participants who had moderate to severe RA and were not responding well to methotrexate treatment.
In RA, the immune system attacks healthy joint tissue, leading to painful and often debilitating symptoms such as joint pain, stiffness, and swelling. Although there is currently no cure, various treatments are available to help manage the symptoms.
When treating moderate to severe rheumatoid arthritis, doctors usually suggest methotrexate as the first treatment. However, most people will also take a tumor necrosis factor inhibitor (TNFi) or a combination of three drugs called triple therapy, which includes methotrexate along with sulfasalazine and hydroxychloroquine, at some point.
Recent research shows that immunomodulatory drugs used to lower inflammation considerably decrease the incidence of heart attacks, strokes, and other cardiovascular events in individuals who have cardiovascular disease.
However, it was uncertain if these medications would have a comparable impact on people who have rheumatoid arthritis, a group that has about a 50% greater chance of experiencing heart disease than the general population.
What did the research involve?
The participants in the new study were randomly assigned to one of two groups.
At the end of six months, both groups experienced comparable reductions in arterial inflammation, which is an indicator of the risk of heart disease, as well as rheumatoid arthritis disease activity.
Dr. Joan Marie Bathon, a professor of medicine at Columbia University College of Physicians and Surgeons and lead author of the study, explained the background to Medical News Today.
“Individuals who have rheumatoid arthritis (RA) are at significantly increased risk for heart attacks and strokes,” she said. “RA is a very inflammatory disease process and the theory is that the increased inflammation in RA is the main risk factor for ‘extra’ cardiovascular risk. [Other risk factors like high blood pressure, diabetes, obesity, etc still play a role as well.]”
Heart attacks are known to occur when atherosclerotic plaques (the fatty areas in the coronary artery walls) -that have the most inflammation- rupture and a clot in the artery ensues. Statins reduce inflammation in the arteries and reduce heart attacks.
Dr. Joan Marie Bathon
Bathon’s key question in this research was to determine whether the anti-inflammatory medications used to treat RA would also reduce inflammation in the arteries.
“If so, could this reduce the ‘excess’ risk for heart attacks and strokes that RA patients have,” Bathon explained.
An imaging scan known as FDG-PET/CT was used to answer this question. FDG lights up arteries that are inflamed and the PET/CT scan detects the inflammation so it can be measured.
The researchers enrolled RA patients who had inflamed joints and needed to add a medication to their existing treatment (which was methotrexate). They randomized the study participants to one of two treatments:
- One was the addition of etanercept or adalimumab to background methotrexate;
- The other was the addition of sulfasalazine and hydroxychloroquine to background methotrexate.
“We did the FDG-PET/CT scans at the beginning of the study and then again after six months of the added treatment,” Bathon said.
We found that RA medications did indeed reduce inflammation in arteries of RA patients, on the order of 8 to 10% (which is about what a moderate dose of a statin would do). We found further that both RA treatment regimens reduced arterial inflammation equivalently. This is the first time that an RA medication has been shown to improve arterial inflammation.
Dr. Joan Marie Bathon
Bathon noted there were limitations to the research.
“Ideally, we would follow patients with arterial inflammation for many years to determine whether they developed a heart attack or stroke, but this would be a mammoth and hugely expensive study requiring thousands of patients. This was not feasible,” she said.
However, she said the research has implications for RA patients and the public.
The implications of this research
If rheumatologists and patients aggressively manage the RA – i.e., get the joint pain and swelling down to very low levels – there is a good chance that that will also result in a reduction of arterial inflammation and that, in turn, will hopefully reduce their risk for future heart attacks and strokes. Of course, individuals with RA should also aggressively work with their doctors to also keep weight, blood pressure, glucose, and cholesterol levels, under good control at the same time.
Dr. Joan Marie Bathon
Dr. Norman B. Gaylis, a master at the American College of Rheumatology who practices in Florida and was not involved in the study, agreed.
He told Medical News Today that “in my opinion, the paper and the topic are extremely important and timely.”
“The correlation between the presence of inflammation being a risk factor for coronary artery inflammation and increased cardiac morbidity has become more understood. This paper actually measures the value of reducing inflammation objectively resulting in reduced inflammation of coronary artery disease,” Gaylis explained.
Using rheumatoid arthritis (RA) as an example of an inflammatory disease and correlating the reduction of inflammation in RA is extremely valuable both for understanding the importance of being proactive in treating RA and inflammation as aggressively as possible and demonstrating how this helps reduce cardiac morbidity.
Dr. Norman B. Gaylis
Gaylis also highlighted that “the unknown danger of not treating inflammation is not necessarily well established or acknowledged by patients and physicians.”
“Whether it’s RA or inflammation of the gums or gastrointestinal tract, there is more evidence that people with chronic inflammation need to be aggressively treated so the inflammation does not remain and cause an increased risk of cardiovascular disease,” he said.
One of the most important things about this paper is it measures a comparison of immune modulators “biologics” versus non-biologic triple DMARD therapy. Both appear to significantly reduce inflammation of the coronary arteries and thereby reduce the morbidity of cardiovascular disease and RA.
Dr. Norman B. Gaylis
“RA or the presence of inflammation presents a need to search for disease activity and inflammation. Overall, physicians and patients must be proactive in trying to reduce and effectively decrease inflammation as much as possible,” Gaylis said.
“This paper is a novel and very important measurement of how reducing inflammation can lower the risk of cardiovascular disease,” he added.
Gaylis concluded by saying “personally, as a rheumatologist who has treated and lectured on the subject of RA for many years, it illustrates the need to aggressively treat and reduce all signs of disease activity and not allow inflammation to smolder in RA patients.“
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