| Title: |
The junctional protein associated with coronary artery disease predicts adverse cardiovascular events in patients with acute coronary syndromes at high residual risk |
| Authors: |
Kraler, Simon; Liberale, Luca; Tirandi, Amedeo; Moriero, Margherita; Wang, Yifan; Farag, Mohamed; Carbone, Federico; Bertolotto, Maria B; Pusterla, Valentina; Ramoni, Davide; Ministrini, Stefano; Puspitasari, Yustina M; Bruno, Francesco; Räber, Lorenz; Di Vece, Davide; Templin, Christian; Muller, Olivier; Mach, François; Crea, Filippo; Camici, Giovanni G; Lapikova-Bryhinska, Tetiana; Akhmedov, Alexander; von Eckardstein, Arnold; Gorog, Diana A; Montecucco, Fabrizio; Lüscher, Thomas F |
| Contributors: |
Kraler, Simon; Liberale, Luca; Tirandi, Amedeo; Moriero, Margherita; Wang, Yifan; Farag, Mohamed; Carbone, Federico; Bertolotto, Maria B; Pusterla, Valentina; Ramoni, Davide; Ministrini, Stefano; Puspitasari, Yustina M; Bruno, Francesco; Räber, Lorenz; Di Vece, Davide; Templin, Christian; Muller, Olivier; Mach, Françoi; Crea, Filippo; Camici, Giovanni G; Lapikova-Bryhinska, Tetiana; Akhmedov, Alexander; Von Eckardstein, Arnold; Gorog, Diana A; Montecucco, Fabrizio; Lüscher, Thomas F |
| Publication Year: |
2025 |
| Collection: |
Università degli Studi di Genova: CINECA IRIS |
| Subject Terms: |
Acute coronary syndrome; Atherosclerosi; Inflammation; JCAD; Junctional protein associated with coronary artery disease; KIAA1462; LDL-c; Lipid; Residual risk; hs-CRP |
| Description: |
Background and aims: Patients with acute coronary syndromes (ACS) are at high ischaemic risk to which cholesterol, inflammation, and yet-to-be-identified pathways jointly contribute. The junctional protein associated with coronary artery disease (JCAD) drives incident cardiovascular events by acting on coagulation and fibrinolysis. This study aimed to assess whether JCAD serves as a novel marker of or target to address residual risk. Methods: In the discovery cohort (SPUM-ACS; n = 4787), ACS patients at residual lipid risk [RLR; on-statin LDL cholesterol (LDL-c) ≥70 mg/dL or ≥1.8 mmol/L], residual inflammatory risk [RIR; on-statin high-sensitivity C-reactive protein (hs-CRP) ≥2.0 mg/L], or both (RILR; on-statin LDL-c ≥70 mg/dL and hs-CRP ≥2.0 mg/L) were identified and compared with propensity-score matched controls. Contributions of hs-CRP, LDL-c and JCAD to recurrent major adverse cardiovascular events (MACE) were analysed. In an independent cohort (RISK-PPCI study; n = 496), effects of JCAD on endogenous coagulation and fibrinolysis were gauged, and JCAD-MACE associations were externally validated. Results: At 1 year, patients at RLR, RIR, or RILR were at higher MACE risk as compared to controls [hazard ratio (HR), 1.55, 95% confidence interval (CI) 1.08-2.23; HR 1.80, 95% CI 1.24-2.61; and HR 1.75, 95% CI 1.12-2.75, respectively]. In those at RLR, MACE risk rose with increasing hs-CRP and JCAD, respectively, in uni- (HR per log2 increase, 1.17, 95% CI 1.06-1.30; HR 1.29, 95% CI 1.03-1.62) and multivariable-adjusted models [adjusted (a)HR 1.16, 95% CI 1.03-1.30; aHR 1.27, 95% CI 1.01-1.60]. In those at RIR, MACE risk increased 1.28-fold per log2 increase in JCAD (HR 1.28, 95% CI 1.03-1.59), which prevailed in multivariable-adjusted models (aHR 1.31, 95% CI 1.04-1.65). Similarly, in patients at RILR, MACE risk increased almost linearly with increasing JCAD (HR 1.45, 95% CI 1.09-1.92), independently of potential confounders (aHR 1.47, 95% CI 1.11-1.97). Plasma levels of JCAD correlated positively with proxies of ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
ELETTRONICO |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41430589; info:eu-repo/semantics/altIdentifier/wos/WOS:001644408400001; firstpage:1; lastpage:16; numberofpages:16; journal:EUROPEAN HEART JOURNAL; https://hdl.handle.net/11567/1281536 |
| DOI: |
10.1093/eurheartj/ehaf979 |
| Availability: |
https://hdl.handle.net/11567/1281536; https://doi.org/10.1093/eurheartj/ehaf979 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.A51346C5 |
| Database: |
BASE |