In severe aortic stenosis, Lp(a) does not track with valve calcium and shows only a modest, male-specific link to fibrosis, CT and cytokine study finds (J Transl Med 2025)

Original title: Systemic inflammation and fibrocalcific remodeling in aortic stenosis: the interplay of Lipoprotein(a), sex, and valve morphology

J Transl Med · 8 October 2025 · 5

Myasoedova VA, Valerio V, Rusconi V, Bertolini F, Massaiu I, Pirola S, Gripari P, Mantegazza V, Cannata F, Stankowski K, Mushtaq S, Pontone G et al.

This prospective study enrolled 45 patients with severe aortic stenosis undergoing preoperative echocardiography and contrast-enhanced cardiac CT at Centro Cardiologico Monzino, quantifying valve calcium and fibrosis volumes and measuring Lp(a) alongside a 44-cytokine Luminex panel, stratified by Lp(a) (50 mg/dL or below vs. above), sex, and bicuspid vs. tricuspid morphology. Median Lp(a) was 34.4 mg/dL (12.6-93.4). No significant difference in valvular calcium load was seen between low and high Lp(a) groups, and only a modest increase in fibrotic volume was noted with elevated Lp(a), more evident in men (P = 0.075). Several cytokines correlated with calcium burden in sex-specific patterns (IL-1RA, IL-8 and TGF-alpha in men; EGF, GM-CSF, IP-10 and IL-10 in women), and bicuspid valves showed higher fibrocalcific volume but lower cytokine levels than tricuspid valves. The authors conclude Lp(a) is not linked to valve calcification in this cohort, and that inflammatory cytokine profiling, with attention to sex and valve morphology, may be more informative for understanding aortic stenosis pathophysiology.

Original abstract

Background: Aortic valve stenosis (AS) is a progressive valvular disease characterized by fibrocalcific remodeling of the aortic valve leaflets, contributing to significant cardiovascular morbidity and mortality. While valve calcification has been extensively studied, the relationship between valve fibrosis, lipoprotein(a) [Lp(a)], systemic inflammation, sex differences, and valve morphology remains less explored.

Methods: We prospectively enrolled 45 patients with severe AS undergoing preoperative echocardiography and contrast-enhanced cardiac computed tomography (CT) at Centro Cardiologico Monzino. Aortic valve calcium and fibrosis volumes were quantified using threshold-based segmentation on CT images. Lp(a) was measured by ELISA, while a multiplex Luminex assay measured a panel of 44 cytokines. Patients were stratified by Lp(a) levels (≤ 50 vs. > 50 mg/dL), sex, and valve morphology (bicuspid vs. tricuspid) to explore associations with the fibrocalcific components of stenotic aortic valves.

Results: The median Lp(a) level was 34.4 mg/dL (12.6; 93.4). No significant differences in valvular calcium load were observed between low and high Lp(a) groups. However, a modest increase in fibrotic volume was noted in patients with elevated Lp(a), particularly among men (p = 0.075). Several cytokines, including IL-1RA, IL-8, and TGF-α in men, and EGF, GM-CSF, IP-10, and IL-10 in women, were positively correlated with calcium burden. Fibrotic volume was associated with elevated eotaxin and PDGF-AA levels, with sex-specific patterns. Patients with bicuspid valve exhibited higher fibrocalcific volumes but lower circulating levels of several cytokines compared to patients with tricuspid valve morphology.

Conclusions: In patients with severe AS, circulating cytokine profiles show sex- and valve-morphology-specific associations with the fibrocalcific composition of the valve. However, Lp(a) was not associated with valvular calcification, and any relationship with fibrosis appeared at most modest, more evident in men. These results support the relevance of inflammatory profiling in assessing AS pathophysiology.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.