Abstract Background Patients without standard modifiable cardiovascular risk factors (SMuRFs) who develop coronary artery disease (CAD) challenge conventional diagnostic paradigms, often leading to delayed recognition and treatment. Despite assumptions of a favourable prognosis, SMuRFless myocardial infarction (MI) patients experience disproportionately high early mortality. Emerging evidence implicates inflammation and endothelial dysfunction in CAD progression, even in the absence of traditional risk factors. Lysozyme, a key innate immune protein, has been linked to vascular inflammation and atherosclerosis, positioning it as a potential biomarker for CAD severity. This study evaluates lysozyme’s diagnostic utility in SMuRFless CAD to improve risk stratification and early intervention. Methods A retrospective analysis was conducted on patients with stable angina, stratifying them based on the presence or absence of SMuRFs (hypertension, diabetes, hyperlipidaemia, and smoking). Plasma lysozyme levels were quantified using enzyme-linked immunosorbent assay (ELISA), alongside additional inflammatory markers. CAD severity was classified into No CAD, Minor CAD, and Significant CAD (Single, Double, or Triple Vessel Disease). Statistical analysis included receiver operating characteristic (ROC) curve assessment to determine lysozyme’s discriminative power. Results Among 111 SMuRFless patients (64% male, mean age 63 years), CAD severity was distributed as follows: 22 No CAD, 20 Minor CAD, 22 Single VD, 19 Double VD, and 28 Triple VD. Lysozyme levels showed a progressive increase with CAD severity (p 0.001): No CAD: 1.0 (IQR 0.3), Minor CAD: 1.1 (IQR 0.3), Single VD: 2.0 (IQR 1.2), Double VD: 3.2 (IQR 1.6) and Triple VD: 11.2 (IQR 3.2). Compared to No/Minor CAD, lysozyme was significantly elevated in Single VD (p 0.001), Double VD (p 0.01), and Triple VD (p 0.001). ROC curve analysis demonstrated excellent diagnostic performance (AUC: 94.0% 95% CI: 89.3%–98.7%). A lysozyme threshold of 1.7 yielded 92.9% sensitivity and 89.9% specificity, distinguishing Significant CAD from No/Minor CAD with high accuracy. Conclusion SMuRFless CAD is an under-recognised yet high-risk entity. Lysozyme emerges as a robust biomarker for CAD severity, with high diagnostic accuracy and strong predictive value. Its stepwise elevation with disease burden highlights its potential role in early detection and risk stratification in this overlooked patient group. Integrating lysozyme into clinical workflows could enhance early intervention and improve outcomes for SMuRFless CAD patients.
Fathieh et al. (2025) studied this question.