Rheumatoid factor-positive arthritis patients may have an increased risk of cardiovascular events associated with steroid use, according to a study from the Mayo Clinic.
Findings from the study, in which 575 individuals were followed for a median of 13 years, also suggest that 7,000 mg prednisone equivalents is the specific cumulative dose beyond which the risk appears, Dr. John M. Davis III said at the annual meeting of the American College of Rheumatology.
A rheumatoid factor-positive patient with that cumulative dose had 3.2 times the risk for a cardiovascular event compared with a rheumatoid factor-positive patient never exposed to steroids.
That increased risk appeared to be present regardless of the patient's demographic status, cardiovascular risk factors such as hypertension or serum lipid level, and disease severity characteristics, said Dr. Davis of the division of rheumatology at the Mayo Clinic, Rochester, Minn.
“This interaction with rheumatoid factor was highly significant,” said Dr. Davis. The possibility that what was observed in the study might have occurred by chance was only 0.6%, he noted.
Increased risk was not found for rheumatoid factor-negative patients, or for rheumatoid factor-positive patients exposed to a lower cumulative dose.
The study subjects were individuals in Rochester who received a diagnosis of rheumatoid arthritis according to American College of Rheumatology criteria between 1955 and 1995. Their complete medical records were reviewed until death, until their last follow-up, or until the end of 2003.
The study excluded patients with heart failure or a myocardial infarction before their diagnosis with rheumatoid arthritis. Cumulative steroid exposure was estimated based on the start and stop dates and doses noted in the records, and did not include any of the times they may have used inhaled steroids. The cardiovascular events considered were myocardial infarction with hospitalization, heart failure, and cardiovascular death.
The investigators used a number of statistical methods on their data to control for the other factors besides steroid exposure that can influence risk.
The study may have missed accurately accounting for disease severity, which might itself be the most important risk factor and which might be reflected by a high use of steroids, Dr. Davis cautioned.
The steroid-use patterns of the rheumatoid factor-positive individuals suggest that they had more severe disease. The percent of rheumatoid factor-positive patients who had used a steroid at 20 years was 68%, compared with 44% of the rheumatoid factor-negative patients. Rheumatoid factor-positive patients' mean duration of steroid use was 2.4 years, versus 1 year in the negative patients.
On the other hand, the rheumatoid arthritis characteristics the study used to gauge severity—and therefore control for it—were many, and included joint swelling, joint surgery, rheumatoid factor, radiographic damage, sedimentation rate, nodules, and vasculitis.
“We cannot rule out the possibility of an interaction, such that glucocorticoids have detrimental effects that are limited to rheumatoid factor-positive patients,” Dr. Davis said in his concluding remarks.
A 7,000-mg, prednisone-equivalent, cumulative dose is equal to taking 7.5 mg of prednisone daily for 3 years, he noted.