Association of oxidized ApoB and oxidized ApoA-I with high-risk coronary plaque features in cardiovascular disease

BACKGROUND. Oxidized apolipoprotein B (oxLDL) and oxidized ApoA-I (oxHDL) are proatherogenic. Their prognostic value for assessing high-risk plaques by coronary computed tomography angiography (CCTA) is missing. METHODS. In a prospective, observational study, 306 participants with cardiovascular disease (CVD) had extensive lipoprotein profiling. Proteomics analysis was performed on isolated oxHDL, and atherosclerotic plaque assessment was accomplished by quantitative CCTA. RESULTS. Patients were predominantly White, overweight men (58.5%) on statin therapy (43.5%). Increase in LDL-C, ApoB, small dense LDL-C (P < 0.001 for all), triglycerides (P = 0.03), and lower HDL function were observed in the high oxLDL group. High oxLDL associated with necrotic burden (NB; β = 0.20; P < 0.0001) and fibrofatty burden (FFB; β = 0.15; P = 0.001) after multivariate adjustment. Low oxHDL had a significant reverse association with these plaque characteristics. Plasma oxHDL levels better predicted NB and FFB after adjustment (OR, 2.22; 95% CI, 1.27–3.88, and OR, 2.80; 95% CI, 1.71–4.58) compared with oxLDL and HDL-C. Interestingly, oxHDL associated with fibrous burden (FB) change over 3.3 years (β = 0.535; P = 0.033) when compared with oxLDL. Combined Met136 mono-oxidation and Trp132 dioxidation of HDL showed evident association with coronary artery calcium score (r = 0.786; P < 0.001) and FB (r = 0.539; P = 0.012) in high oxHDL, whereas Met136 mono-oxidation significantly associated with vulnerable plaque in low oxHDL. CONCLUSION. Our findings suggest that the investigated oxidized lipids are associated with high-risk coronary plaque features and progression over time in patients with CVD. TRIAL REGISTRATION. ClinicalTrials.gov NCT01621594. FUNDING. National Heart, Lung, and Blood Institute at the NIH Intramural Research Program.