Switzerland: Researchers have found in a new study that Junctional protein associated with coronary artery disease (JCAD) has emerged as a promising biomarker for residual cardiovascular risk following acute coronary syndrome (ACS). Elevated JCAD levels were associated with a higher likelihood of adverse cardiovascular outcomes despite standard therapy, indicating their potential role in risk stratification, prognostication, and personalized post-ACS management.In the study published in the European Heart Journal, Simon Kraler from the University of Zurich, Zurich, Switzerland, and colleagues explored whether JCAD could help explain the persistent ischaemic risk seen in many ACS patients even after receiving guideline-recommended lipid-lowering and anti-inflammatory therapies. While cholesterol and inflammation are well-recognized contributors to post-ACS risk, the authors noted that additional pathways, particularly those related to coagulation and fibrinolysis, may play a crucial role in driving recurrent events.The investigators first analysed data from the SPUM-ACS cohort, which included 4,787 patients with ACS. Participants were categorized based on residual lipid risk, defined as on-statin LDL cholesterol levels of at least 70 mg/dL (1.8 mmol/L); residual inflammatory risk, defined as on-statin high-sensitivity C-reactive protein levels of 2.0 mg/L or higher; or the presence of both risk phenotypes. These patients were compared with propensity score–matched controls to assess the contribution of JCAD, LDL cholesterol, and hs-CRP to the occurrence of major adverse cardiovascular events (MACE) within one year. Key Findings:Patients with residual lipid risk, residual inflammatory risk, or both had a significantly higher risk of major adverse cardiovascular events (MACE) compared with matched control patients.JCAD consistently predicted adverse cardiovascular outcomes across all residual risk categories.In patients with residual lipid risk, higher JCAD levels were independently associated with an increased risk of MACE, even after accounting for traditional risk factors and inflammatory markers.Among patients with residual inflammatory risk, rising JCAD concentrations were linked to a meaningful increase in recurrent cardiovascular events.In patients with both residual lipid and inflammatory risk, MACE risk increased almost linearly with higher JCAD levels and remained significant after multivariable adjustment.The association between JCAD and MACE was confirmed in an independent external validation cohort from the RISK-PPCI study involving 496 patients.Higher plasma JCAD levels were correlated with markers of impaired endogenous fibrinolysis in the validation cohort.These findings suggest a mechanistic link between elevated JCAD, reduced clot breakdown, and increased thrombotic risk.Overall, the findings highlight that a substantial proportion of ACS patients remain at high risk of recurrent cardiovascular events despite optimal control of LDL cholesterol and inflammation. By consistently predicting adverse outcomes across different residual risk phenotypes and showing links to impaired fibrinolysis, JCAD stands out as a potential novel biomarker and therapeutic target.The authors emphasize that future studies are needed to determine whether targeting JCAD can effectively reduce ischaemic risk and improve long-term outcomes in this vulnerable post-ACS population.Reference:Kraler, S., Liberale, L., Tirandi, A., Moriero, M., Wang, Y., Farag, M., Carbone, F., Bertolotto, M. B., Pusterla, V., Ramoni, D., Ministrini, S., Puspitasari, Y. M., Bruno, F., Räber, L., Di Vece, D., Templin, C., Muller, O., Mach, F., Crea, F., . . . Lüscher, T. F. The junctional protein associated with coronary artery disease predicts adverse cardiovascular events in patients with acute coronary syndromes at high residual risk. European Heart Journal. https://doi.org/10.1093/eurheartj/ehaf979