Cardio Risk in RA: Not Just Heart Attacks and Strokes

Rates of aortic stenosis were almost 50% higher in U.S. veterans with rheumatoid arthritis (RA) relative to other individuals in the Veterans Affairs health system, researchers found.

Incidence rates for aortic stenosis were 3.97 per 1,000 patient-years of observation among RA patients versus 2.45 per 1,000 patient-years in non-RA controls, according to Bryant England, MD, PhD, of the University of Nebraska Medical Center in Omaha, and colleagues.

Writing in JAMA Internal Medicine, the researchers reported a hazard ratio of 1.48 (95% CI 1.41-1.55) for aortic stenosis risk with an RA diagnosis, after adjusting for variables including race/ethnicity, BMI, smoking, healthcare utilization, and comorbidity burden.

That RA patients face increased risk for cardiovascular disease is well known. However, clinical studies to date have mostly examined arterial atherosclerosis and adverse cardiovascular events such as myocardial infarction and heart failure, England and colleagues noted. But some research has also pointed to valvular disease as another contributor to cardiovascular death in RA patients. Conceivably this could help explain why standard cardiovascular risk models are relatively inaccurate in RA patients.

“Aortic stenosis is the most common reason for valve replacement and the most frequent cause of valvular heart disease-related death in the U.S.,” the group observed.

As such, they argued, aortic stenosis “may be an overlooked cardiovascular disease complication in RA.”

To examine the issue quantitatively, England and colleagues turned to VA health system data, identifying some 73,000 patients with RA. Each was matched with up to 10 non-RA patients in the VA system according to age, sex, and VA enrollment year, for a total of almost 640,000 controls.

Since VA patients are mostly military veterans, most in this study were men (87.6% in the RA group, to be exact). Mean ages was 63 and 62 for RA and control patients, respectively, and just under three-quarters were white. Follow-up averaged about 9 years, such that it totalled 6.2 million patient-years in total. More of the RA patients had smoking histories (81% vs 68% for controls), and also had more comorbidities on average, with mean Rheumatic Disease Comorbidity Index values of 1.7 versus 1.2.

Some 16,000 aortic stenosis cases were diagnosed during follow-up, and roughly one-quarter underwent interventions including surgical or transcatheter valve replacements.

Deaths related to aortic stenosis (i.e., an ICD-10 code for the condition was listed as the underlying cause) occurred at rates of 0.17 and 0.11 in the RA and control groups, respectively. This equated to a hazard ratio of 1.26 (95% CI 1.04-1.54) — “a mortality risk similar to that of ischemic heart disease in previous RA cohorts,” England and colleagues observed.

The researchers also identified several markers of increased risk for aortic stenosis in the RA group. These included elevated C-reactive protein and erythrocyte sedimentation rate and use of common RA medications such as corticosteroids and biologic or other targeted anti-rheumatic drugs. However, while achieving statistical significance, these associations were not especially strong, with adjusted hazard ratios in the range of only 1.11-1.22. Also, aortic stenosis appeared more common in white patients than in others, less so in women than in men, and more so with increasing age. No associations were seen, however, between aortic stenosis risk and overweight/obesity or with the presence of RA-specific biomarkers such as rheumatoid factor.

Among the study’s limitations, the most prominent was its use of VA data and thus the overwhelming dominance of male patients. In the general population, roughly 70%-80% of RA cases occur in women; thus, the generalizability outside the VA population could be questioned. Also, the study relied on administrative records that could contain errors, and not all possible confounding variables (such as smoking intensity, blood lipid levels, or genetics) were captured.

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