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Abstract
Structural valve degeneration (SVD) is the leading cause of late bioprosthetic valve failure. Lipoprotein(a) [Lp(a)] contributes to native aortic valve calcification, but its role in SVD is unclear. We investigated whether elevated Lp(a) is associated with SVD after bioprosthetic aortic valve replacement (AVR), and whether this differs between stenotic and regurgitant phenotypes. We studied 174 bioprosthetic AVR patients with available Lp(a) levels over a median echocardiographic follow-up of 7.3 years (1,372 studies). SVD was defined by VARC-3 criteria, and associations were analyzed with Fine-Gray competing risk models. Lp(a) was evaluated categorically (≤ or > 125 nmol/L) and continuously using spline modeling. During follow-up, 40 patients developed SVD (22 stenotic, 9 mixed, 9 regurgitant). The 15-year cumulative incidence was 51% with median onset at 14.8 years. Elevated Lp(a) was associated with higher risk of overall SVD (62% vs 47%; SHR 2.06, 95% CI 1.09-3.91; p=0.026) and specifically with stenotic/mixed phenotypes (SHR 2.57, 95% CI 1.26-5.23; p=0.009). No association was observed with regurgitant phenotypes (SHR 0.85, 95% CI 0.19-3.92; p=0.84). After multivariable adjustment, elevated Lp(a) remained an independent predictor of stenotic/mixed SVD (adjusted SHR 3.00, 95% CI 1.48-6.07; p=0.002). Spline modeling showed a linear dose-response, with each 25 nmol/L increase in Lp(a) conferring 13% higher risk. Elevated Lp(a) is independently associated with long-term risk of stenotic/mixed SVD. These findings highlight Lp(a) as a promising biomarker of prosthetic valve vulnerability and support investigation of emerging Lp(a)-lowering therapies to improve valve durability.
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Boute, M., Salembier, P., Pouleur, A.-C., Pasquet, A., Gerber, B., De Azevedo, D., Gruson, D., de Kerchove, L., Kefer, J., Beauloye, C., Horman, S., Maes, F., Pierard, S., & Vancraeynest, D. (2025). Lipoprotein(a) and long-term structural valve degeneration of aortic bioprostheses. European heart journal. Cardiovascular Imaging, 1-10. https://doi.org/10.1093/ehjci/jeaf320 (Original work published 2025)