Glucocorticoids and cardiovascular events in rheumatoid arthritis: A population‐based cohort study

Abstract

Objective. To determine the relationship between glucocorticoid exposure and cardiovascular (CV) events in patients with rheumatoid arthritis (RA).Methods. A total of 603 adult residents of Rochester, Minnesota with incident RA between 1955 and 1995 were followed up through their medical records for a median of 13 years (total of 9,066 person-years). Glucocorticoid exposure was defined 3 ways: tertiles of cumulative exposure; recent use (<3 months) versus past use (>3 months); and average daily dosage (<7.5 mg/day or >7.5 mg/day). CV events, including myocardial infarction, heart failure, and death from CV causes, were defined according to validated criteria. Cox regression models were adjusted for demographic features, CV risk factors, and RA characteristics.Results. Rheumatoid factor (RF)-negative patients with exposure to glucocorticoids were not at increased risk of CV events, irrespective of the glucocorticoid dosage or timing of use, as compared with the reference group of RF-negative patients who had never been exposed to glucocorticoids. In contrast, RFpositive patients were at increased risk of CV events, particularly with higher cumulative exposure, higher average daily dosage, and recent use of glucocorticoids. RF-positive patients with high cumulative exposure to glucocorticoids had a 3-fold increased risk of CV events (hazard ratio 3.06 [95% confidence interval 1.81-5.18]), whereas RF-negative patients with high cumulative exposure were not at increased risk (hazard ratio 0.85 [95% confidence interval 0.39-1.87]).Conclusion. RF-positive but not RF-negative patients were at increased risk of CV events following exposure to glucocorticoids. These findings suggest that glucocorticoids interact with RF status to modulate the occurrence of CV events in patients with RA. The mechanisms underlying this interaction are unknown and should be the subject of further research.

Glucocorticoids and Cardiovascular Disease

“…In a Canadian cohort of O40 000 subjects, no excess risk of heart failure with glucocorticoid exposure was identified (101). In a smaller US cohort, a dose-dependent risk of cardiovascular disease with glucocorticoid exposure was confirmed, but was only detectable amongst rheumatoid factor-positive patients (102). Studies in other disease groups have probably been too small to be confident of their findings.…”

Balancing benefits and risks of glucocorticoids in rheumatic diseases and other inflammatory joint disorders: new insights from emerging data. An expert consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)

“…Since there was evidence to link GC use with the increased risks for diabetes and hypertension, confounding likely accounted for the observed association between GC use and the overall risk of MI [102]. It remains possible however that some interaction exists between RF-positivity and exposure to glucocorticoids in the risk of CV events [103]. Longer-term GC use in the medium dose range in patients with RA has been linked with hypertension [104] and it may also increase the risk of venous thromboembolism [105].…”

Atherosclerosis: An Extra Articular Manifestation of Rheumatoid Arthritis

“…Glucocorticoids also affect lipid panel [17], hence judicious use of glucocorticoids is warranted in RA patients with traditional risk factors.…”