Exploratory Analysis of the Innate Immune System in Aortic Stenosis Patients With and Without ASCVD

Calcific aortic valve disease (CAVD) leads to aortic stenosis (AS) through inflammation and fibro-calcific remodeling. Although CAVD and atherosclerosis share features, not all patients with AS develop atherosclerotic cardiovascular disease (ASCVD), suggesting mechanistic heterogeneity. This case-control study evaluated inflammatory profiles and valvular remodeling in 128 patients with AS (59.4% with ASCVD) and 105 controls. Immune cell composition and monocyte markers were analyzed by flow cytometry, whereas cytokine production was assessed after peripheral blood mononuclear cell (PBMC) stimulation. Both AS groups had higher interleukin (IL)-6, leukocyte, monocyte, and neutrophil counts than controls, with lower monocyte human leukocyte antigen-DR isotype and higher C-C chemokine receptor (CCR)2 expression. Cytokine responses were also elevated, particularly in AS patients with ASCVD. They also showed higher IL-6 concentrations, higher proportions of classical monocytes, and lower intermediate and non-classical monocytes compared with patients without ASCVD. Overall, AS was associated with a pro-inflammatory monocyte phenotype and function, most prominently in patients with ASCVD. ClinicalTrials.gov ID: NCT04717219.