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Plasmatic PCSK9 Levels Are Associated with Very Fast Progression of Asymptomatic Degenerative Aortic Stenosis


The aim of this work was to study the association of potential biomarkers with fast aortic stenosis (AS) progression. Patients with moderate-to-severe AS were classified as very fast progressors (VFP) if exhibited an annualized change in peak velocity (aΔVmax) ≥0.45m/s/year and/or in aortic valve area (aΔAVA) ≥−0.2cm2/year. Respective cut-off values of ≥0.3m/s/year and ≥−0.1cm2/year defined fast progressors (FP), whereas the remaining patients were non-fast progressors (non-FP). Baseline markers of lipid metabolism, inflammation, and cardiac overload were determined. Two hundred and nine patients (97 non-FP, 38 FP, and 74 VFP) were included. PCSK9 levels were significantly associated with VFP (OR 1.014 [95%CI 1.005-1.024], for every 10 ng/mL), as were active smoking (OR 3.48) and body mass index (BMI, OR 1.09), with an AUC of 0.704 for the model. PCSK9 levels, active smoking, and BMI were associated with very fast AS progression in our series, suggesting that inflammation and calcification participate in disease progression.

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This study was funded by the Fundació La Marató de TV3 (REF 2015-1910).

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Corresponding author

Correspondence to Begoña Benito.

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Ethical Approval

All procedures performed in the present study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Clinical Relevance

• In this prospective study including 209 patients with asymptomatic moderate-to-severe degenerative AS, we found that active smoking, BMI, and levels of PCSK9 are predictors of a particularly fast progression of the disease. Our data suggest, therefore, that inflammation and subsequent calcification could be important mechanisms of AS progression.

• Our results are novel in that they suggest that PCSK9 levels could help in predicting a very rapid AS progression.

• Moreover, our results set the basis to assess the potential benefit of intensive preventive strategies to reduce modifiable risk factors such as smoking and BMI associated with fast AS progression.

Associate Editor Craig M. Stolen oversaw the review of this article

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Cite this article

Mateos, N., Gómez, M., Homar, A. et al. Plasmatic PCSK9 Levels Are Associated with Very Fast Progression of Asymptomatic Degenerative Aortic Stenosis. J. of Cardiovasc. Trans. Res. (2021).

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  • Aortic stenosis
  • Biomarkers
  • Disease progression
  • PCSK9
  • Body mass index
  • Smoking