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Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein
Published on: October 12, 2017
Association of oxidized ApoB and oxidized ApoA-I with high-risk coronary plaque features in cardiovascular disease
Alexander V Sorokin1, Christin G Hong1, Angel M Aponte2
1Section of Inflammation and Cardiometabolic Diseases, Cardiovascular Branch.
Insights
Oxidized low-density lipoprotein (oxLDL) and oxidized high-density lipoprotein (oxHDL) are linked to high-risk coronary plaque features. OxHDL levels better predict plaque characteristics and progression over time in cardiovascular disease patients.
Area of Science:
- Cardiovascular Research
- Lipidomics
- Biomarker Discovery
Background:
- Oxidized apolipoprotein B (oxLDL) and oxidized ApoA-I (oxHDL) are proatherogenic, but their prognostic value in assessing high-risk coronary plaques via CCTA is not well-established.
- Understanding the role of these oxidized lipoproteins is crucial for improving cardiovascular risk stratification.
Purpose of the Study:
- To investigate the prognostic value of oxLDL and oxHDL in assessing high-risk coronary plaques.
- To correlate oxidized lipoprotein levels with specific plaque characteristics and progression using quantitative CCTA.
Main Methods:
- A prospective, observational study involving 306 participants with cardiovascular disease (CVD).
- Extensive lipoprotein profiling, proteomics analysis of isolated oxHDL, and quantitative CCTA for atherosclerotic plaque assessment.
- Multivariate regression analysis to adjust for clinical confounders.
Main Results:
- High oxLDL was associated with increased necrotic and fibrofatty plaque burden.
- Low oxHDL showed a significant inverse association with these plaque characteristics.
- Plasma oxHDL levels demonstrated superior predictive value for necrotic and fibrofatty burden compared to oxLDL and HDL-C.
- OxHDL levels correlated with fibrous plaque progression over 3.3 years and with coronary artery calcium score.
Conclusions:
- Investigated oxidized lipids, particularly oxHDL, are significantly associated with high-risk coronary plaque features.
- Oxidized lipoproteins are linked to plaque progression over time in CVD patients.
- OxHDL shows promise as a biomarker for assessing coronary plaque vulnerability and progression.
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.
Clinicaltrials:
gov NCT01621594.
Funding:
National Heart, Lung, and Blood Institute at the NIH Intramural Research Program.
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