Serum myeloperoxidase/paraoxonase 1 ratio as potential indicator of dysfunctional high-density lipoprotein and risk stratification in coronary artery disease.

OBJECTIVE: Granular leukocyte-derived myeloperoxidase (MPO) promotes oxidation of lipoproteins, while paraoxonase 1 (PON1) has antioxidant properties for high-density lipoprotein (HDL). We evaluated their effects on coronary risk stratification and function of lipoproteins.

METHODS AND RESULTS: A total 158 patients who had previously undergone percutaneous coronary intervention and who had been hospitalized for coronary re-angiography were enrolled. Coronary lesions (restenosis or de novo lesion) were observed in 84 patients but not associated with conventional lipid profile. In contrast, serum MPO levels and PON1 activities were significantly associated with the prevalence of coronary lesions. The high MPO/PON1 ratio, when cutoff values were set at 1.59, was independently correlated with restenosis (odds ratio 6.4, 95% CI 2.2-19.3, P = 0.001) and de novo lesions (odds ratio 3.5, 95% CI 1.3-9.4, P = 0.014). We isolated HDL from patients with high or low MPO/PON1 ratio, and compared anti-inflammatory properties of HDL. Human umbilical vein endothelial cells were stimulated with inflammatory cytokine, and the expression of vascular cell adhesion molecule-1 (VCAM-1) was evaluated. HDL isolated from patients with low serum MPO/PON1 ratio inhibited VCAM-1 expression significantly greater than that with high MPO/PON1 ratio. We also demonstrated that the cholesterol efflux capacity of apolipoprotein B-depleted serum from patients with high MPO/PON1 ratio was significantly decreased than that with low MPO/PON1 ratio.

CONCLUSIONS: MPO/PON1 ratio could be a useful marker for secondary prevention of coronary artery disease through modulation of HDL function.