PHILADELPHIA — The increased atherosclerotic disease that generally accompanies rheumatoid arthritis may not consistently involve carotid artery stenosis, according to two reports at the annual meeting of the American College of Rheumatology.

In a study with 195 RA patients and a nearly equal number of controls, carotid atherosclerosis was not clearly linked with coronary atherosclerosis in RA patients, although the link existed in controls, said Dr. Jon T. Giles, a rheumatologist at Johns Hopkins Medical Center in Baltimore.

Results from a second study, a meta-analysis of 22 prior reports in a total of 1,384 RA patients, showed that the average extent of carotid intima-media thickness was “far less than expected.” Patients' average carotid stenosis corresponded to about a 10%–15% increase in cardiovascular risk, compared with similar people without RA, said Dr. Michael T. Nurmohamed, a rheumatologist at the Free University Medical Center in Amsterdam.

But the relationship between RA and carotid disease is more complex, according to a second set of results reported by Dr. Nurmohamed. Preliminary results from measurement of carotid intima-media thickness in 100 patients with RA showed a mean thickness of 0.83 mm, which is “comparable” to the carotid thickness in patients with type 2 diabetes—and enough stenosis to produce “a significantly increased cardiovascular risk,” Dr. Nurmohamed said.

“For now, there is no recommendation on how to measure” subclinical cardiovascular disease, Dr. Giles said in an interview. No one can say whether measuring coronary disease is better or worse than measuring carotid atherosclerosis. If an RA patient “does not have carotid atherosclerosis, you can't be comfortable that nothing is going on,” he said.

The study he reported included 195 RA patients who were seen at the arthritis center at Johns Hopkins during October 2004–May 2008 and were enrolled in the ESCAPE-RA (Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis) study. Patients were 45–84 years old at enrollment and met the 1987 ACR classification criteria for RA.

Enrollment excluded patients with clinically apparent cardiovascular disease, including those with a history of MI, heart failure, stroke, and peripheral vascular disease. For this analysis, RA patients were matched by age, sex, and ethnicity with 198 controls who did not have RA and who had been enrolled in the Baltimore cohort of MESA (Multi-Ethnic Study of Atherosclerosis). Carotid intima-media thickness was measured by B-mode ultrasound, and coronary calcium was measured by multidetector row CT. The results showed that carotid stenosis was linked to a high level of coronary calcium in both RA patients and controls. But many RA patients without carotid atherosclerosis nonetheless had an increased prevalence of coronary calcium, an incongruous combination that was not seen in the controls.

“The absence of carotid atherosclerosis cannot rule out coronary atherosclerosis in RA patients in the same way that it does in the general population,” Dr. Giles said. The implication is that “using subclinical carotid atherosclerosis as a surrogate for coronary atherosclerosis in studies of RA patients may be inaccurate.”

The meta-analysis of 22 studies by Dr. Nurmohamed and his associates involved a total of 1,147 controls and more than 1,300 RA patients. In 17 of the studies, the carotid intima-media thickness was greater in the RA patients than in the controls. But the average intima-media thickness in the RA patients was 0.71 mm, an average of 0.09 mm larger than in the controls, a difference that corresponds to a modest 10%–15% higher rate of cardiovascular risk. The low risk level may have occurred because the studies excluded people with cardiovascular disease or risk factors at baseline, a step that may have led to an underestimate of the difference in carotid intima-media thickness between the RA patients and controls.

The carotid data collected directly by Dr. Nurmohamed and his associates came from the CARRÉ (Cardiovascular Research and Rheumatoid Arthritis) study. A report from CARRÉ showed the substantially higher level of cardiovascular disease events in 294 patients with RA (13%), compared with 258 controls (5%) (Ann. Rheum. Dis. 2009;68:1395–400). So far, Dr. Nurmohamed and his associates have measured the carotid intima-media thickness in 100 of these RA patients. In this preliminary assessment, the average intima-media thickness in RA patients was 0.83 mm, a level high enough to produce a significant risk for cardiovascular events. The carotid atherosclerosis in RA patients showed no link with inflammatory parameters or with disease duration, Dr. Nurmohamed said. Additional prospective, controlled studies are needed to further define the cardiovascular disease risk in RA patients, he added.

Neither Dr. Giles nor Dr. Nurmohamed has any disclosures relevant to their research to report.

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RA patients' carotid stenosis corresponded with 'a significantly increased cardiovascular risk.'

Source DR. NURMOHAMED

Doubts Cast on Tight Link Between RA and Carotid Disease