Patients With RA Are at Increased Risk for Aortic Stenosis, Study Suggests

Patients with rheumatoid arthritis (RA) are more vulnerable to aortic stenosis (AS) and valvular heart disease–related death, according to a study published in JAMA Internal Medicine.

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Valvular heart disease is one of the larger contributors to cardiovascular disease (CVD)–related mortality in patients with RA. In cases of valvular heart disease, AS is responsible for the majority of necessitated valve replacement and mortality in patients. As the authors of the present study note, a wealth of literature supports the associations between the inflammatory nature of RA and CVD risks; however, a connection between AS and RA remains unknown and understudied. To address this gap, researchers investigated the risks for AS and AS-related outcomes associated with RA.

Data were gathered from the national Veterans Health Administration (VHA) and CMS between 2000 and 2019. Patients identified with RA were matched by age, sex, and year of VHA enrollment with up to 10 patients without RA (controls). Individuals were excluded if they underwent any aortic valve intervention prior to the study. All of those included were followed up until the end of the study period, their first AS outcome, or death.

The primary outcomes researchers looked for were incident AS (either diagnosed during an inpatient or outpatient assessment), aortic valve intervention, or death related to AS. Additionally, patient comorbidity burdens were quantified through the Rheumatic Disease Comorbidity Index (RDCI, where higher scores represent higher comorbidity). Risk factors for AS were also evaluated by extracted erythrocyte sedimentation rates (ESR), C-reactive protein levels (CRP), and rheumatoid factor or anti-cyclic citrullinated protein (RF or anti-CCP).

A total of 73,070 patients with RA were included and matched with 639,268 controls. At baseline, 68.9% of patients with RA came back with seropositive results for RF or anti-CCP and 47% exhibited elevated ESR or CRP levels.

In total, 16,109 AS outcomes were identified—2303 of which occurred in patients with RA—over 6,223,150 person-years. Patients’ mean follow-up time was approximately 8 years in those with RA and almost 9 years in controls. The mean onset age between the 2 groups was similar (74.9 vs 75.5 years, respectively). Those affected by RA endured a 1.52 more AS events per 1000 person-years compared to controls (composite, 3.97 vs 2.45). These incidences involved increased rates of AS-related incidences (adjusted HR [AHR], 1.48) and death (AHR, 1.26). The authors note that increased risks for valvular interventions related to AS were linked with RA (AHR, 1.34).

The study’s results confirm previous analyses that suggest valvular carditis risk can be influenced by inflammatory and immune intermediaries. Their findings suggest that valvular heart disease could be a lesser-known influence of CVD-related mortality in patients with RA. The authors conclude by mentioning, “In addition to inflammation due to RA disease activity, patients with RA are disproportionately affected by multimorbidity and metabolic syndrome, which may contribute to higher systemic inflammation and poorer AS-related outcomes.” They encourage future studies be conducted to further understand the role inflammatory pathways play in AS severity and risk in patients with RA.

Reference

Johnson TM, Mahabir CA, Yang Y, et al. Aortic stenosis risk in rheumatoid arthritis. JAMA Intern Med. 2023;183(9):973-981. doi:10.1001/jamainternmed.2023.3087