RA stroke risk nearly rivals that seen with hypertension

Skin & Allergy News, Feb, 2008 by Diana Mahoney

BOSTON -- Rheumatoid arthritis patients' well-known increased risk for stroke is greater than previously appreciated. The autoimmune condition confers nearly as much risk for the cerebrovascular outcome as does hypertension, according to findings from a large trial reported at the annual meeting of the American College of Rheumatology.

Patients with rheumatoid arthritis have a well-documented increased risk for coronary artery disease and myocardial infarction (MI). In an interview, investigator Dr. Christopher Edwards said it is difficult to be certain if the same processes are involved in MI and stroke. "They are likely similar, but subtle and important differences may be present. More work is needed to establish this," he said.

In a nested case-control study using the United Kingdom General Practice Research Database, which comprises the medical records of more than 7 million patients, Dr. Edwards, along with lead investigator Dr. Alison Endean and colleagues at the University of Southampton (England), looked at the incidence of stroke and its important risk factors in rheumatoid arthritis patients, compared with the general population.

The investigators identified 33,191 adults with a diagnosis of rheumatoid arthritis who were enrolled in the database between June 1987 and April 2002, as well as 99,570 age-, sex-, and medical practice--matched controls. Patients who had a stroke before being diagnosed with rheumatoid arthritis were not included in the analysis.

The main outcome was stroke defined by the International Classification of Diseases, Ninth Revision codes for cerebrovascular disease, including diagnoses of intracerehral hemorrhage, other intracranial hemorrhage, occlusion and stenosis of precerebral arteries, occlusion of precerebral arteries, and acute but ill-defined cerebrovascular disease.

The investigators conducted person-year and Poisson regression analyses to analyze the incidence rate ratios of stroke and the effects of traditional risk factors (including age, sex, body mass index, smoking, diabetes, hypertension, myocardial infarction, heart failure, renal failure, and hyperlipidemia); treatment with steroids; and treatment with disease-modifying antirheumatic drugs (DMARDs).

With respect to baseline characteristics, patients with rheumatoid arthritis were significantly more likely to be smokers and to have cardiac failure, compared with the controls, noted Dr. Edwards.

In the rheumatoid arthritis group, there were 883 stroke diagnoses, compared with 2,146 in the control group. "The incidence of stroke was almost 3 [per 1,000 patients per year] in the general population and around 5.7 in individuals with rheumatoid arthritis," said Dr. Edwards. "The [rheumatoid arthritis] patients had a 67% higher risk for stroke than healthy controls."

In both groups, the traditional risk factors were associated with increases in the incidence rate ratios for stroke.

In the multivariate analysis, rheumatoid arthritis continued to be associated with a significantly increased incidence rate ratio, said Dr. Edwards. "The incidence rate ratio for stroke in rheumatoid arthritis patients was 1.65, which is only slightly lower than the incidence rate ratio for hypertension at time of stroke, which was 1.72."

In terms of treatment effect, the use of prednisolone was associated with a nearly 30% increase in stroke risk, compared with nonuse, and there was a nonsignificant trend toward higher stroke risk associated with methotrexate, Dr. Edwards noted. No significant effects were associated with DMARD therapy, either alone or in combination with other drugs, he said. About 50% of patients were treated with DMARDs, the most common being sulfasalazine.

Dr. Edwards noted in the interview that because the data were gathered on patients treated between 1987 and 2002, there is inadequate information regarding whether use of anti-tumor necrosis factor-[alpha] agents affects the risk.

The findings provide additional insight into the disease burden facing rheumatoid arthritis patients, said Dr. Edwards.

BY DIANA MAHONEY

New England Bureau