Introduction Structural valve degeneration (SVD) leads to the failure of aortic valve bioprostheses. It is suspected that lipid-derived factors could play a role in SVD. We hypothesised that oxidised low-density lipoprotein (OxLDL), OxLDL/LDL, OxLDL/high-density lipoprotein (OxLDL/HDL) and proprotein convertase subtilisin/kexin 9 (PCSK9) may be associated with SVD.
Methods We included 199 patients who underwent an aortic valve replacement with a bioprosthesis and had an echocardiography follow-up to evaluate the function of the prosthesis. SVD was defined as an increase in mean transprosthetic gradient (≥10 mm Hg) or a worsening of transprosthetic regurgitation (≥1/3) during the follow-up.
Results After a mean follow-up of 8±3.5 years, 41(21%) patients developed SVD. The univariate predictors of SVD were LDL (p=0.03), apolipoprotein B (p=0.01), OxLDL (p=0.02), OxLDL/HDL (p=0.009) and LDL associated with small, dense particles (LDL-C<255Å) (p=0.02). In a model adjusted for covariates, only OxLDL/HDL (OR 1.49, 95%CI 1.08 to 2.07 per 10 units, p=0.01) remained associated with SVD. There was a significant interaction between OxLDL/HDL and PCSK9 on SVD (p=0.05). After adjustment, compared with patients with low OxLDL/HDL (median, <25.4) and low PCSK9 (median, <298 ng/mL) (referent), patients with both an elevated OxLDL/HDL ratio and PCSK9 had a higher risk of SVD (OR 2.93, 95% CI 1.02 to 9.29, p=0.04).
Conclusions OxLDL/HDL ratio is independently associated with SVD.
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Contributors MJN, AM and PM conceived the experimental plan and conducted analyses. MJN, AM, M-CB and RB measured biomarkers. BJA and J-PD measured the size of LDL. EL performed and analysed CT. PP supervised echo analyses. HM reviewed echo analyses. AD participated to the recruitment of patients. All the authors critically reviewed the manuscript and participated to its intellectual content.
Funding This work was supported in part by CIHR grants to PM MOP114893, MOP245048, MOP341860, the Heart and Stroke Foundation of Canada and the Quebec Heart and Lung Institute Fund. AM was supported by a studentship grant from the Quebec Heart and Lung Institute Fund. YB holds a Canada Research Chair in Genomics of Heart and Lung Diseases. PP holds the Canada research Chair in Heart Valve Disease. BJA is a junior research scholar from the Fonds de Recherche du Québec-Santé (FRQS). PM holds a FRQS Research Chair on the Pathobiology of Calcific Aortic Valve Disease.
Competing interests None declared.
Ethics approval The protocol was approved by the Local Ethical Committee (Quebec Heart and Lung Institute).
Provenance and peer review Not commissioned; externally peer reviewed.
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