P5305Oxidized high-density lipoprotein is associated with progression of coronary artery calcification

Introduction As a residual cardiovascular risk, high-density lipoprotein (HDL) is of great interest in lipid management. Native HDL has an anti-atherogenic role, while oxidized HDL (oxHDL) has atherogenic property because of reduced anti-inflammatory properties compared with native HDL. Meanwhile, recent studies showed that rapid progression of coronary artery calcification (CAC), a marker of subclinical atherosclerosis, was associated with greater incidence of cardiovascular events. However, the role of oxHDL in the pathogenesis of CAC remains unclear. Purpose The purpose of this study was to examine the association between the annual change in oxHDL and the progression of CAC (Agatston score) in a substudy of prospective multicenter randomized study. Methods In the principal study, patients with a CAC score of 1 to 999 were treated with pitavastatin with/without eicosapentaenoic acid. Measurement of CAC with MDCT and a blood test were performed at baseline and at the 1-year follow-up. The principal study showed 30–40% of annual change in CAC in all patients and no difference in the progression of CAC among treatment groups. In this substudy (n=140), patients were divided into 2 groups: CAC progression (change in Agatston score of >0, n=103) and no CAC progression (n=37). The serum concentration of oxHDL was measured using an antibody against oxidized human apoA-I with ELISA. The difference in oxHDL between patients with hypercholesterolemia and healthy subjects (n=30) was also evaluated. Results OxHDL levels were significantly lower in healthy subjects than in patients with hypercholesterolemia (150 [107–176] and 167 [132–246], respectively; median [25th-75th percentile], U/ml) (p=0.006). The baseline log-transformed oxHDL level was correlated with total cholesterol (r=0.21, p=0.01), HDL-cholesterol (r=0.33, p<0.01), and triglycerides (r=−0.21, p=0.01), but not correlated with age, body mass index, hemoglobinA1c, LDL-cholesterol, serum creatinine, or high-sensitivity C-reactive protein. After treatment, the oxHDL level significantly decreased from 167 (132–246) at baseline to 122 (103–149) (median [25th–75th percentile], U/ml) (p<0.001). The annual change in CAC was significantly positively associated with changes in oxHDL (r=0.17, p=0.04), triglycerides (r=0.17, p=0.04), and hsCRP (r=0.22, p=0.01) but not associated with changes in LDL-C or HDL-C. Multiple logistic analysis demonstrated that the decrease in oxHDL per 10 U/ml was independently associated with CAC progression after adjusting for variables including baseline oxHDL, LDL-cholesterol, Agatston score and current smoking (odds ratio, 0.95; 95% confidence interval, 0.90–0.99; p=0.04). Conclusion The decrease in oxHDL is associated with the attenuation of CAC progression, suggesting that oxHDL is a potential target for preventing atherosclerosis.