BOSTON, Massachusetts—A nested case-control study that compared the risk of stroke in rheumatoid arthritis (RA) patients with the risk in the general population found that RA is an independent risk factor for stroke. The British research team led by Alison L. Endean, MBChB, also found that RA increases that risk nearly as much as having hypertension (HTN). They reported their findings at the 2007 ACR meeting.¹

Co-investigator Christopher J. Edwards, MD, of the department of rheumatology at Southampton General Hospital in the UK, said, "Rheumatoid arthritis is known to be associated with an increased risk of myocardial infarction (MI). These unique data suggest that the disease is associated with an increased risk of stroke as well. Appropriate risk assessment and intervention for this important cause of morbidity and mortality in RA is clearly a critical issue."

Among the factors considered in this analysis, the researchers found significantly elevated incidence rate ratios (IRR) for stroke associated with

• RA 1.65 (P <.001)
• Smoking (current/ex versus never) 1.27 (P <.001)
• HTN 1.72 (P <.001)
• Diabetes (DM) 1.99 (P <.001)

Prednisolone was associated with an IRR of 1.29 (P = .010). There was not significant effect on stroke risk with other DMARDs +/- MTX; with MTX + prednisolone; or with MTX, prednisolone + other DMARDs.

The researchers used the United Kingdom General Practice Research Database, which includes the medical records comprising diagnosis (ICD-9 codes) and prescriptions of >7 million patients. They were able to identify most RA patients in primary, secondary, and tertiary care and each patient was control-matched for factors including age, sex, and medical practice.

The main outcome was stroke defined by ICD-9 codes for cerebrovascular disease; IRRs of stroke in RA patients were compared with controls. Multivariate analysis included the effects of traditional risk factors (age, sex, BMI, smoking, DM, HTN, MI, heart and renal failure, and hyperlipidemia), treatments for traditional risk factors, and use of steroids and DMARDs.

"Excluding cases of stroke diagnosed prior to diagnosis of RA and their controls, there were 33,191 RA cases and 99,570 controls," Dr. Endean wrote. "There were 883 incidences of stroke in cases and 2146 in controls. Traditional risk factors were associated with increases in IRR in both cases and controls. In the multivariate analysis RA continued to be associated with a significantly higher IRR 1.65 (95% CI 1.44-1.88) P <.001."

There was an increasing trend with time from RA diagnosis, but adjusting for age rendered this insignificant.

"In this large nested case control study RA was an independent risk factor for stroke. Prednisolone when used alone was associated with increased risk. DMARDs did not have a statistically significant effect although there was a trend towards increased risk in those on MTX," Dr. Endean concluded.

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