Higher Stroke, AF Risk in Rheumatoid Arthritis

Pauline Anderson

March 13, 2012

March 13, 2012 — Patients with rheumatoid arthritis (RA) have a 40% increased risk of atrial fibrillation (AF) and a 30% increased risk of stroke compared with those without RA, a new Danish study has found.

The study shows what its authors called a "remarkable" 3-fold increase in the relative risk for both AF and stroke in patients with RA who are younger than 50 years, though the absolute differences in rates were highest in the oldest patients.

The results suggest that the annual examination of patients with RA should include screening for AF, said lead author Jesper Lindhardsen, MD, research fellow at the department of cardiology, Copenhagen University Hospital Gentofte, Hellerup, Denmark.

Dr. Jesper Lindhardsen

There have been discrepancies in reports about stroke risk in patients with RA and, although previous research showed that these patients are at increased risk for myocardial infarction, this study is the first to assess their AF risk, Dr. Lindhardsen told Medscape Medical News.

The study was published online March 8 in the British Medical Journal.

Registry Data

Researchers used several national registries to access information on medical diagnoses and drug treatments for all Danish citizens. From a total population of 4.3 million, 18,247 people were identified as having RA with a female predominance of about 70%, and a mean age at disease onset of 59.2 years.

During a span of 13 years, 165,343 people, including 718 with RA, had a stroke and 156,484, including 774 with RA, were diagnosed with AF.

The age- and sex-matched event rates for AF were 8.2 per 1000 person years for patients with RA and 6.0 per 1000 person years for the general population, resulting in an AF incidence that was about 40% higher in patients with RA. Women were at slightly higher relative risk than men. The absolute risk attributable to RA ranged from 25% in the oldest to 70% in the youngest patients.

The results correspond to 1 new case of AF for every 12 patients with RA followed for 10 years after diagnosis.

For stroke, the rates were 7.6 per 1000 person years in patients with RA and 5.7 per 1000 person years in the general population, for an overall increased risk of 30%. Again, the relative risk was highest in the younger age groups but with absolute differences in incidence rates increasing with age.

The finding that the risk of AF and stroke is higher among younger patients with RA, who tend not to have other diseases, suggests that AF and RA are closely connected, said Dr. Lindhardsen. "The finding hints that it is indeed RA disease that can cause an increased risk of AF."

It also confirms the role that inflammation likely plays in AF, he said. If this is the case, controlling inflammation could be key not only to managing joint symptoms in patients with RA, but also to reducing the need for drugs that may have adverse cardiovascular effects.

However, Dr. Lindhardsen noted that the absolute numbers of patients with RA who had AF in the study are "very low" among those younger than age 50 years.

The study should serve as a reminder to clinicians that all patients with RA are at increased overall cardiovascular risk, said Dr. Lindhardsen. He stressed that because the stroke risk associated with AF can be reduced significantly with appropriate treatment, diagnosing AF is very important to reduce the burden of cerebrovascular disease.

Current Screening

Current guidelines recommend annual screening for cardiovascular risk factors, which include blood pressure, cholesterol, smoking, age, and gender, in patients with RA. "AF has not been considered in the current screening programs," said Dr. Lindhardsen. "We suggest that it might be a good idea to consider including it."

Dr. Lindhardsen pointed out that screening for AF is easy, inexpensive, and noninvasive. "The simple addition of a pulse check, checking to see if the pulse is irregular, and of course asking patients if this is a problem, could extend the value of the annual screening," he said. It could also lead to follow-up with electrocardiography if needed.

The increased incidence of AF in patients with RA may not be that surprising. Heart failure is strongly associated with AF (and vice versa) and may explain some of this increased risk.

Patients with RA show increased atrial stiffness which is a risk factor for both heart failure and AF. Glucocorticoids and nonsteroidal anti-inflammatory drugs used by many RA patients also are a risk factor for AF.

Reports on the RA-related risk of stroke are conflicting. One recent meta-analysis concluded that the risk for myocardial infarction, but not stroke, was significantly increased in patients with RA, but another study found a 2-fold increased risk for both stroke and MI.

Among the strengths of the study were its large size and the fact that the cohort was "unselected" in that it included all residents of Denmark, said Dr. Lindhardsen.

"Much Ado About Little"

However, asked to comment on the study, Nortin M. Hadler, MD, professor of medicine and attending rheumatologist, University of North Carolina at Chapel Hill, said the study results would not influence the clinical management of his own patients with RA.

That is because Dr. Hadler believes that large administrative data sets such as those used in this study are "seductive for statisticians who enjoy mining data," but are likely to include "irrelevant and irreproducible" and possibly "fallacious" associations.

"That is particularly true when the magnitude of the association is as slight as in this example," Dr. Hadler told Medscape Medical News. "If you follow 1000 patients with RA for a year and 1000 without, only 2 extra cases of AF might occur in the RA group, so I tend to place studies such as this in the 'much ado about very little' category."

His examination of patients with RA already includes a cardiovascular assessment, Dr. Hadler added.

The authors have disclosed no relevant financial relationships.

BMJ. Published online March 8, 2012. Abstract


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