Polymorphic size of Lipoprotein (a) and structural bioprosthetic valve degeneration

Abstract Background The use of biological heart valves (BHV) is constantly growing for the treatment of patients with aortic stenosis and their durability arises as a main concern in the field. Structural valve deterioration (SVD) of the BHV occurs gradually post-implantation and seems to reiterate, at least in part, the pathophysiological processes described in native valve stenosis. Lipoprotein (a) [Lp(a)] is an important genetically determine cardiovascular risk factors, associated with native valve calcification. The shorter polymorphic sizes of Lp(a), defined as low of apolipoprotein (a) [apo(a)] Kringle-IV copy number, have been associated with more deleterious cardiovascular phenotype. However, the association of Lp(a) plasma levels and/or its polymorphic sizes with SVD remains unclear. Purpose To determine whether Lp(a) plasma levels and/or the Lp(a) polymorphic size were associated with SVD. Methods 332 patients who underwent aortic valve replacement (AVR) with BHV from the Translink trial were included in this study. Clinically significant SVD has been defined as Stage 3 SVD based on the VARC-3 definition. Lp(a) concentration was determine by immunoturbidimetry method and the apo(a) Kringle-IV copy number by liquid chromatography-tandem mass spectrometry. Univariable and multivariable models, adjusted for clinically relevant and statistically significant variables, were used to determine the independent association between Lp(a) concentrations or apo(a) Kringle-IV copy numbers with SVD. Results Among the 332 patients included in this study, the mean age was 78 ±8 years and 71% were males. 76 patients (23%) presented clinically significant SVD. Low apo(a) Kringle-IV copy number was associated with an increased risk of SVD (per log decrease: OR=2.71 [1.34-5.50], p=0.006), but not Lp(a) plasma concentration (OR=0.99 [0.84-1.15], p=0.85). This association remained significant after comprehensive multivariable adjustments, including Lp(a) concentration (OR=3.21 [1.31-7.84], p=0.01). The analysis of the transprosthetic mean gradient, as a surrogate marker of SVD, provided consistent results (all p≤0.03). Conclusion This cross-sectional study from the Translink trial demonstrates the association between Lp(a) polymorphic size and SVD, highlighting a potential therapeutic option to limit the occurrence of SVD in selected patients who underwent AVR with surgical or transcatheter BHV.