Elevated Lp(a) in severe AS patients is linked to ~20% higher transvalvular gradients and significantly increased valve calcification and fibrosis-related proteins.
Is elevated Lipoprotein(a) associated with increased valvular calcification and proteomic changes in patients with severe aortic stenosis?
In patients with severe aortic stenosis, elevated Lp(a) is associated with more pronounced valve calcification and upregulation of proteins involved in tissue remodeling and inflammation.
Absolute Event Rate: 0% vs 0%
Abstract Background Elevated lipoprotein(a) Lp(a) increases the risk of aortic stenosis (AS); however, the role of Lp(a) in valvular tissue remodeling and fibro-calcification in AS remains unclear. Aims To assess associations between elevated Lp(a) and valvular fibrosis and calcification as well as changes in the valvular proteome in severe AS. Methods We recruited 30 symptomatic AS patients (69±6 years), 11 of whom had Lp(a) levels ≥50mg/dL (high Lp(a) group) and 19 had Lp(a) levels 50mg/dL (normal Lp(a) group). Routine tests measured Lp(a), glucose, creatinine, lipid profile and CRP. Proteomic analysis of calcified and non-calcified valve regions (5 from each Lp(a) group) was performed using mass spectrometry. The structural characteristics of valvular calcification were examined ex vivo using micro-CT, including bone volume (BV), surface volume (SV), and trabecular thickness (TbThmax). Results No intergroup differences were observed in demographics, risk factors, medication use, or laboratory parameters, except for higher total and LDL cholesterol levels in high Lp(a) patients (both p0.05). High Lp(a) patients had 11.6% increased peak transvalvular velocity (Vmax) and about 20% higher both transvalvular gradients (PGmean, PGmax) compared to normal Lp(a) subjects (all p0.05). Among the detected valvular proteins high Lp(a) patients had 11.7-fold higher apolipoprotein(a), 9.8-fold higher calmodulin 1 (CALM1, involved in calcium signaling), 7.8-fold higher calcium-binding protein (S100-B) and 4.7-fold higher Wnt11 (implicated in valve calcification) compared to normal Lp(a) subjects. Calcified valve regions compared to non-calcified regions showed 54.6-fold higher macrophage metalloelastase (MMP-12), 31.6-fold higher CRP, 25.1-fold higher phospholipid transfer protein (PLTP), 20.5-fold higher cholesteryl ester transfer protein (CETP), 19.8-fold higher plasminogen activator inhibitor 1 (PAI-1) and 11.2-fold higher transforming growth factor-β (TGF-β). Micro-CT showed less calcium deposits within leaflets of patients with normal Lp(a) compared to high Lp(a) subjects (Figure 1A-B). Valves from normal Lp(a) patients showed reduced BV (-77.9%), SV (-69.3%) and TbThmax (-17.6%) compared to high Lp(a) (all p0.05). Lp(a) correlated with PGmean (r=0.36, p=0.047) and with micro-CT indices, including BV, SV and TbThmax (Figure 1C-E). Additionally, BV and SV correlated with PGmean (r=0.44, p=0.016 and r=0.38, p=0.038). Conclusions In severe AS patients elevated Lp(a) is associated with more pronounced valve calcification and higher level of proteins involved in different molecular pathways such as tissue remodelling, inflammation, lipid metabolism, fibrinolysis and calcification, expressed mainly within calcified regions.Figure 1
Kopytek et al. (Sat,) reported a other. Elevated Lp(a) in severe AS patients is linked to ~20% higher transvalvular gradients and significantly increased valve calcification and fibrosis-related proteins.