The junctional protein associated with coronary artery disease predicts adverse cardiovascular events in patients with acute coronary syndromes at high residual risk

Despite major advances in early revascularization and secondary prevention, a substantial proportion of patients with a recent acute coronary syndromes (ACS) remain at high residual ischaemic risk to which cholesterol, inflammation, and yet-to-be-identified pathways jointly contribute.
In this study, published in the European Heart Journal, patients with a recent ACS at residual lipid risk (on-statin LDL cholesterol (LDL-c)≥70 mg/dL or ≥1.8 mmol/L), residual inflammatory risk (on-statin high-sensitivity C-reactive protein (hs-CRP) ≥2.0 mg/L), or combined risk (on-statin LDL-c ≥70 mg/dL and hs-CRP ≥2.0 mg/L) experienced a significantly higher incidence of recurrent major adverse cardiovascular events at 1 year as compared to matched controls, underscoring the persistent unmet need beyond guideline-recommended LDL-c and hs-CRP lowering.

Initially identified by genome-wide association studies (GWAS), the junctional protein associated with coronary artery disease (JCAD) is causally involved in atherosclerosis and consistently predicted adverse outcomes across all residual risk phenotypes, whereas LDL-c and hs-CRP showed limited or no independent prognostic value within these high-risk groups. Mechanistically, aligning with previous work, JCAD correlated strongly with prothrombotic mediators, impaired endogenous fibrinolysis, and recurrent events in the RISK-PPCI study, suggesting a central role for thrombotic vulnerability across residual risk strata.
These findings support the concept that residual risk after ACS is driven not only by cholesterol and inflammation, but also by additional pathobiological pathways that are likely insufficiently targeted by currently available therapies. By linking endothelial dysfunction to downstream coagulation and fibrinolytic imbalance, JCAD appears to integrate key processes underlying atherothrombosis.

Collectively, these data position JCAD as a novel biomarker of residual cardiovascular risk and a potential therapeutic target beyond lipid- and inflammation-centred strategies in patients with a recent ACS. Targeting JCAD-related pathways may therefore represent a complementary approach to further reduce ischaemic events in patients with ACS receiving contemporary care.