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Randomized Controlled Trial
. 2025 Mar;55(3):e14359.
doi: 10.1111/eci.14359. Epub 2024 Nov 23.

Ceramide and phosphatidylcholine lipids-based risk score predicts major cardiovascular outcomes in patients with heart failure

Angelika Witoslawska  1 , Jennifer M T A Meessen  2 , Mika Hilvo  3   4 , Antti Jylhä  3 , Faiez Zannad  5 , Marianna Cerrato  2 , Patrick Rossignol  5 , Deborah Novelli  2 , Kevin Duarte  5 , Giovanni Targher  6   7 , Roberto Latini  2 , Nicolas Girerd  5 , Reijo Laaksonen  1   3
Affiliations
Randomized Controlled Trial

Ceramide and phosphatidylcholine lipids-based risk score predicts major cardiovascular outcomes in patients with heart failure

Angelika Witoslawska et al. Eur J Clin Invest. 2025 Mar.

Abstract

Background: Ceramide and phosphatidylcholine lipids-based risk score (CERT2) has shown a strong prognostic value in predicting cardiovascular (CV) events in patients with ischemic heart disease. This study aimed to investigate the prognostic value of CERT2 risk score in patients with heart failure (HF).

Methods: The current study combines data for 4234 subjects from the COMMANDER-HF trial and 1227 subjects from the GISSI-HF trial, which enrolled patients with a history of HF. The CERT2 risk score was calculated for all the participants as previously described. The primary outcome was CV death, but all-cause death and major adverse CV events (three-point MACE) were analysed as well.

Results: After adjustment for established CV risk factors and potential confounders, patients with the highest CERT2 risk category remained at almost three-fold higher risk of CV death (COMMANDER-HF: HR 2.80, 95% CI 2.18-3.60, GISSI-HF: 2.84, 95% CI 1.70-4.74), all-cause death (COMMANDER-HF: HR 2.97, 95% CI 2.36-3.75, GISSI-HF: 2.83, 95% CI 1.83-4.38) and MACE (COMMANDER-HF: HR 2.73, 95% CI 2.20-3.38, GISSI-HF: 2.67, 95% CI 1.67-4.26) compared to those with the lowest CERT2 risk category.

Conclusions: The CERT2 risk score is strongly associated with an increased risk of CV death, all-cause death and MACE in patients with HF.

Keywords: cardiovascular event; ceramides; plasma biomarkers; risk score; sphingolipids.

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Conflict of interest statement

Zora Biosciences Oy holds patent disclosures related to the diagnostic and prognostic use of ceramides and phospholipids in CVD. M.H., A.J., and R.L. are employees and R.L. a shareholder of Zora Biosciences Oy. All other authors have nothing to disclose. This work has been supported by Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia), project ERAPERMED2022‐113, GA779282 under the frame of ERA PerMed. The GISSI‐HF clinical trial was funded by Società Prodotti Antibiotici (SPA; Italy), Pfizer, Sigma Tau, and AstraZeneca.

Figures

FIGURE 1
FIGURE 1
Kaplan–Meier curves of the progressively increased risks for CV death, all‐cause death and MACE.
FIGURE 2
FIGURE 2
Kaplan–Meier curves of NT‐proBNP for CV death, all‐cause death and MACE.
See this image and copyright information in PMC

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