New Blood Marker Predicts Coronary Artery Disease with Striking Accuracy

Coronary artery disease remains the leading cause of death worldwide, yet current biomarkers like LDL cholesterol often fail to capture the full picture of individual risk. Identifying new blood-based markers that reflect the biology of plaque formation could transform how clinicians assess and manage cardiovascular risk.

This study focused on the interaction between LL-37, a human cathelicidin antimicrobial peptide known to have roles in inflammation and immunity, and ApoB-100, the structural protein of LDL and other atherogenic lipoproteins. Using surface plasmon resonance and protein docking analysis, the researchers confirmed that LL-37 physically binds to multiple sites on ApoB-100, forming a detectable circulating complex. They then developed a specific antibody to measure this complex in blood plasma.

In a case-control study of 1,103 patients across two independent centers who underwent coronary angiography, plasma LL-37-ApoB-100 levels were significantly elevated in those with obstructive coronary artery disease. Levels correlated strongly with the Gensini score, a measure of disease severity, with a correlation coefficient of 0.60. Receiver operating characteristic analysis yielded an area under the curve of 0.82. Crucially, elevated complex levels remained an independent predictor after adjusting for lipids and clinical variables, with an adjusted odds ratio of 6.51 for the highest quartile. Findings were replicated in a second independent cohort and were supported by mouse model data showing the complex tracks with atherosclerotic plaque area.

If validated in prospective studies, the LL-37-ApoB-100 complex could become a clinically useful tool for identifying patients at elevated cardiovascular risk, particularly those who might be missed by conventional lipid testing. The biological mechanism — linking innate immune activation with lipoprotein-driven plaque formation — also opens new research directions for understanding and potentially targeting atherosclerosis.