VIENNA, Austria-Methotrexate (MTX) given concomitantly with folic acid slashes risk of cardiovascular disease (CVD) by 70% in RA patients, according to a new study presented here on Friday at the Annual European Congress of Rheumatology of the European League Against Rheumatism (EULAR). However, when researchers controlled for folic acid, this protective effect disappeared, suggesting that it is largely folate's effect on serum homocysteine that is driving the decreased risk, explains lead researcher Paco MJ Welsing, MSc, of Radboud University Nijmegen Medical Center in The Netherlands. Folic acid is frequently prescribed with MTX to reduce toxicities.

In the study of 544 patients from the Nijmegen inception cohort of early RA who had not used a DMARD prior to the study, MTX was the only drug that decreased CVD risk. Sulfasalazine, hydroxychloroquine, and steroids did not affect the risk, nor did biologics or cyclooxygenase-2 (COX-2) drugs, although Welsing cautions that few patients in the study were taking the latter two.

Disease activity influences heart disease risk in RA patients

The new study also found that increases in disease activity as assessed by the Disease Activity score (DAS-28) are a risk factor for heart disease among RA patients. During the study, which had an average of 11 years of follow-up, DAS-28 scores were assessed every 3 months.

Such increases in disease activity may well be on par with traditional heart disease risk factors such as hyperlipidemia and hypertension. "I would think so, but we did not make a formal comparison," Welsing tells CIAOMed. For every incremental increase on the DAS-28, participants had a 1.7 increased risk of heart attack and stroke.

"We have to treat disease activity," Welsing stresses, and "when we do so with MTX and folic acid, incidence of CVD will likely decrease," he adds.

The session moderator Ted Mikuls, MD, rheumatologist at the University of Nebraska Medical Center in Omaha, called the new findings "good news," telling CIAOMed that "we treat our patients early and aggressively and can potentially prevent the leading cause of death in patients with rheumatoid arthritis."

During the new study, 14% of patients had angina, 11% had a myocardial infarction, 8% had cerebrovascular disease, 10% had peripheral vascular disease, and 26% had hypertension. Welsing et al also measured functional disability every 6 months using the Health Assessment Questionnaire Disability Index (HAQ-DI) and joint damage every 3 years using the modified Sharp score.

Reference:

Welsing PMJ, Kievet W, Fransen J, et al. The relation of disease activity and methotrexate with the risk of cardiovascular disease in patients with rheumatoid arthritis. Presented at: Annual European Congress of Rheumatology of EULAR; June 8-11, 2005; Vienna, Austria. Abstract OP0103.