Surprise RA link to aortic stenosis

3 minute read


Study data provide an additional argument to treat RA to a target low disease activity level.


A large US cohort study has found an increased risk of aortic stenosis in people with rheumatoid arthritis.

The study, published in JAMA Internal Medicine, reported that people with RA had a 48% increased risk of AS, independent of traditional cardiovascular risk factors, when compared with matched controls.

People with RA were also 34% more likely to have an aortic valve intervention, suggesting a more severe disease course necessitating procedural intervention, and had a 26% increased risk of AS-related death.

The authors said that the findings emphasise the potentially underrecognised contribution of valvular heart disease to the cardiovascular disease-related mortality gap in RA patients.

“We hope that these findings highlight to providers that aortic stenosis and valvular heart disease should be considered in addition to CV diagnoses more often studied, such as coronary artery disease and heart failure when thinking about cardiovascular risk in RA,” lead author Dr Tate Johnson of the University of Nebraska Medical Center told Rheumatology Republic.

“This could be applied, for instance, to an RA patient with exercise intolerance or shortness of breath that might be mistakenly attributed to reduced functional status as a product of their articular disease alone”, said Dr Johnson.

“As part of their evaluation, providers should think about valvular heart disease in this scenario and consider echocardiographic screening.”

Using data from US medical databases, the researchers included around 73,000 patients with RA and 640,000 matched controls without RA and followed them up for an average of 8-9 years.

Primary outcome was incident AS, a composite of AS diagnosis, aortic valve intervention (including surgical aortic valve replacement and transcatheter aortic valve replacement) and AS-related death. Secondary outcomes were these individual components.

Being mainly from the Veterans Health Administration database, the cohort was mostly male (around 87%), and had a mean age of 63.

There were 3.97 AS events per 1000 person-years in the RA group, compared with 2.45 events per 1000 person-years in the controls, representing an absolute increase in risk of 1.52 AS events per 1000 person-years. After adjusting for potential confounders, the adjusted hazard ratio was 1.48.

Age, BMI and hypertension were independently associated with an increased risk of AS, while female patients and Black or Hispanic patients had a lower risk.

There was a modest increase in AS risk among patients with elevated baseline ESR or CRP levels, with the authors suggesting that more severe disease activity might be linked with a higher risk of developing AS.

Patients who received “more aggressive RA treatments”, such as b/tsDMARDs and glucocorticoids, were also more likely to develop AS, adding further support to the association between disease severity and AS, the authors said.

“These data were in line with results of preclinical studies suggesting that higher degrees of systemic inflammation were a risk factor for AS in patients with RA and a factor in AS progression in a prior RA cohort,” wrote the authors.

“Continued research is warranted to elucidate the inflammatory pathways mediating AS risk and severity in RA cohorts.”

The main limitations of the study were the small absolute risk difference and the lack of generalisability to the RA population – as mentioned earlier, the cohort was mainly males, whereas RA is more common in females.

“While additional study is needed to understand whether we can accurately risk stratify patients for aortic stenosis, or if specific RA treatment strategies are more effective in reducing valvular heart disease risk, these data can perhaps be used as an additional argument to treat RA to a target low disease activity level,” Dr Johnson told Rheumatology Republic.

JAMA Internal Medicine 2023, Online 31 July

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