Identification and Assessment of Plasma Lysozyme as a Putative Biomarker of Atherosclerosis

OBJECTIVE: To identify a plasma biomarker of atheromatous disease. METHODS AND RESULTS: Surface-enhanced laser desorption ionization-time-of-flight mass spectrometry was used to identify possible plasma protein biomarkers of atheromatous disease in patients presenting with chronic stable angina pectoris by comparing those with 3-vessel disease with those without any evidence of coronary artery disease. The level of a 14.7-kDa protein was elevated; this protein was isolated and identified as a lysozyme. Arterial plasma lysozyme levels, measured by immunoassay, confirmed this observation in separate cohorts of patients. The application of arterial plasma lysozyme levels to 197 patients with varying degrees of coronary artery disease, using a cutoff value of 1.5 microg/mL, was able to distinguish patients with 1 or more occluded coronary arteries, with 86% sensitivity and 93% specificity. Of 20 patients with carotid atheroma, 19 had increased arterial plasma levels. In contrast, C-reactive protein levels showed no association with disease severity. Venous lysozyme levels in patients with carotid atheroma were shown to decrease after intensive atorvastatin treatment. CONCLUSION: Raised plasma lysozyme levels may be a useful biomarker of atherosclerotic cardiovascular disease and response to therapy. Additional studies to investigate this are warranted.