PB0522 - The Combination of Lipocalin-2 and Calprotectin Improves Risk Assessment in Advanced and Early Peripheral Arterial Disease

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

GS

Goren Saenz-Pipaon

PhD student
CIma universidad de Navarra
Pamplona, Navarra, Spain
SR

Susana Ravassa

PhD
CIma universidad de Navarra
Pamplona, Navarra, Spain
KL

Katrine Lawaetz-Larsen

MD, PhD
Elite Centre of Medical Treatment of Arterial Diseases
Odense, Syddanmark, Denmark
EM

Esther Martínez-Aguilar

MD, PhD
Complejo Hospitalario de Navarra
Pamplona, Navarra, Spain

Presenting Author(s)

Josune Orbe, PhD

Researcher
Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra
Pamplona, Navarra, Spain

Co-Author(s)

JR

Jose A. Rodriguez

PhD
Cima Universidad de Navarra
Pamplona, Navarra, Spain
LF

Leopoldo Fernandez-Alonso

MD, PhD
Complejo Hospitalario de Navarra
Pamplona, Navarra, Spain
AG

Arantxa Gonzalez

PhD
Cima Universidad de Navarra
Pamplona, Navarra, Spain
JM

Jose Luis Martin-Ventura

Professor
IIS-Fundación Jiménez-Díaz, Universidad Autonoma de Madrid; CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Madrid, Madrid, Spain
JP

Jose Antonio Páramo

Hematology Service
Clínica Universidad de Navarra
Pamplona, Navarra, Spain
JS

Jes Sanddal Lindholt

Professor
Department of Cardiac, Thoracic, and Vascular Surgery, Odense University Hospital, Odense, Denmark
Odense C, Syddanmark, Denmark
Carmen Roncal, PhD

Researcher
Cima Universidad de Navarra
Pamplona, Navarra, Spain

Background: It is important to find reliable markers assessing cardiovascular (CV) risk in peripheral artery disease (PAD). Previous transcriptomic analyses in plasma extracellular vesicles (EVs) revealed increased expression of calprotectin (S100A8/A9) and lipocalin 2 (LCN2) in PAD patients.

Aims: The aim of this study was to determine their prognostic value for CV risk assessment in PAD.

Methods: EVs were isolated from plasma and femoral plaques to determine LCN2 and calprotectin by qPCR and western blot. Their expression was also determined in human femoral plaques by immunohistochemistry. LCN2 and calprotectin were measured by ELISA in advanced PAD (CHN cohort, n=331, serum), and early PAD (VIVA trial, n=413, plasma). Patients were followed up for a mean of four years, recording as combined outcome CV death or amputation (CHN cohort) and CV death or major lower limb events (MALE, VIVA population).

Results: LCN2 and S100A9 were detected in plasma and femoral plaque EVs, and in femoral atherosclerotic tissues in regions rich in inflammatory cells. Increased levels of both proteins were associated with a higher risk of CV death or amputation (5.6-fold after covariate adjustment, p<.001), and CV death or MALE (3-fold, multivariate analysis, p<.001) in the CHN cohort and the VIVA trial respectively. Moreover, the addition of the combined variable to basal models, considering clinically relevant risk factors, improved reclassification for the studied outcome in both cohorts (p≤.024).

Conclusion(s): The transcriptomic analysis of circulating EVs (liquid biopsy) partially reflects both systemic and local changes (molecular signature), and enabled the identification of new prognostic biomarkers in PAD. Moreover, the combined assessment of LCN2 and calprotectin might be useful for risk stratification in advanced and early PAD.

Funding: Ministry of Science and Innovation, Institute of Health Carlos III, co-funded by the European Fund for Economic and Regional Development (FEDER) [PI18/01195 and CB16/11/00371]. Virto Group (Spain).