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CC BY 4.0 · Thromb Haemost
DOI: 10.1055/a-2717-3194
Atherosclerosis and Ischaemic Disease

PCSK9 Predicts Adverse Limb Outcomes After Endovascular Revascularization in Diabetic Chronic Limb-threatening Ischemia

Authors

  • Federico Biscetti    ‡

    1   Cardiovascular Internal Medicine Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
    2   Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Roma, Italy

  • Maria Margherita Rando   ‡

    1   Cardiovascular Internal Medicine Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy

  • Maria Anna Nicolazzi

    1   Cardiovascular Internal Medicine Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy

  • Giorgia Polito

    1   Cardiovascular Internal Medicine Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
    2   Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Roma, Italy

  • Giovanni Pecorini

    1   Cardiovascular Internal Medicine Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
    2   Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Roma, Italy

  • Flavia Angelini

    2   Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Roma, Italy

  • Roberto Iezzi

    3   Radiology Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma, Italy

  • Luis H. Eraso

    4   Division of Vascular and Endovascular Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, United States

  • Paul J. Dimuzio

    4   Division of Vascular and Endovascular Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, United States

  • Dario Pitocco

    5   Diabetology Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma, Italy

  • Massimo Massetti

    6   Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy

  • Antonio Gasbarrini

    2   Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Roma, Italy
    7   Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy

  • Andrea Flex

    1   Cardiovascular Internal Medicine Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
    2   Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Roma, Italy
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Abstract

Background and Aims

Proprotein convertase subtilisin/kexin type-9 (PCSK9) plays a crucial role in pathophysiologic processes leading to limb and cardiovascular complications in diabetes, including cholesterol homeostasis, inflammation, and endothelial oxidative stress. This study examined the association between PCSK9 levels and major adverse limb events (MALEs) in patients with type 2 diabetes mellitus (T2DM) and chronic limb-threatening ischemia (CLTI) after endovascular revascularization.

Methods

This prospective cohort study included 147 T2DM patients with peripheral artery disease undergoing endovascular revascularization for CLTI. Clinical assessments, including PCSK9 blood levels, were performed, and patients were followed for 12 months to monitor MALEs. Logistic regression and ROC curve analyses assessed the relationship between PCSK9 and MALEs.

Results

During follow-up, 53 patients experienced MALEs. These patients were younger and had more severe peripheral artery disease. PCSK9 levels were significantly higher in those with MALEs (410.5 ng/mL) versus those without (360.6 ng/mL). ROC analysis showed that adding PCSK9 to cardiovascular risk factors improved MALE prediction. PCSK9 levels and Rutherford 4 category were independent risk factors for MALEs.

Conclusion

Elevated PCSK9 levels are strongly associated with increased MALE risk in T2DM patients and may influence age of presentation and disease severity in CLTI. These findings highlight PCSK9 as a potential predictive biomarker and therapeutic target for vascular complications.

Keywords

peripheral arterial disease (PAD) - chronic limb-threatening ischemia (CLTI) - proprotein convertase subtilisin/kexin type-9 (PCSK9)

Data Availability Statement

The datasets generated during the current study are available from the corresponding author upon reasonable request. A.F. is the guarantor of this work and, as such, has full access to all the data in the study and takes responsibility for data integrity and data analysis accuracy.


Contributors' Statement

F.B. and M.M.R.: conceptualization; M.M.R. and F.B.: methodology; M.A.N. and G.P.: data collection; F.A.: immunoassays; F.B.: data analysis; A.F. and D.P.: resources; R.I.: endovascular procedures; A.F.: data curation; M.M.R.: writing—original draft preparation; F.B., A.F., P.D., and L.E.: review and editing; M.M., A.G., and A.F.: supervision. All authors read and approved the final manuscript.


Ethical Approval

The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy. Informed consent was obtained from all subjects involved in the study.


‡ These authors contributed equally to this work.




Publication History

Received: 10 March 2025

Accepted: 18 May 2025

Accepted Manuscript online:
08 October 2025

Article published online:
17 October 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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