Decrease in oxidized high-density lipoprotein is associated with slowed progression of coronary artery calcification: Subanalysis of a prospective multicenter study

Background and aims: Oxidized high-density lipoprotein (oxHDL) is characterized by reduced anti-inflammatory properties compared with HDL. However, the role of oxHDL in the pathogenesis of coronary artery calcification (CAC), a marker of subclinical atherosclerosis, remains unclear. We prospectively investigated the association between the change in oxHDL and progression of CAC in a substudy of a multicenter study.

Methods: In the principal study, patients with a CAC score of 1-999 were treated with pitavastatin with/without eicosapentaenoic acid. Measurement of CAC with multidetector-row computed tomography and a blood test were performed at baseline and at the 1-year follow-up. In the principal study, the increase in CAC did not differ among treatment groups. In this substudy, patients were divided into two groups: CAC progression (change in Agatston score of >0) and no CAC progression.

Results: In total, 140 patients were analyzed. The oxHDL level significantly decreased from 167 (132-246) at baseline to 122 (103-149) after treatment (median [25^th-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 high-sensitivity C-reactive protein (r = 0.22, p = 0.01) but was not associated with changes in low-density lipoprotein cholesterol or HDL-cholesterol. Multiple logistic analysis demonstrated that the decrease in oxHDL per 10 U/ml was independently associated with CAC progression (odds ratio, 0.95; 95% confidence interval, 0.90-0.99; p = 0.04).

Conclusions: The decrease in oxHDL is associated with the attenuation of CAC progression, suggesting that oxHDL is a potential target for atherosclerosis prevention.