Low-density lipoprotein 4: a novel predictor of coronary artery disease severity

Background: Hyperlipidemia is a well established risk factor for coronary artery disease (CAD). Severe CAD has been observed in patients with normal levels of total and low-density lipoprotein (LDL) cholesterol. Small dense LDL particle subtypes (LDL₃ and LDL₄) have been observed to be more oxidizable and atherogenic. We aimed to identify the role of cholesterol particle subtypes in predicting CAD severity. Methods: Blood samples were obtained immediately before cardiac catheterization in 179 consecutive patients with suspected CAD. Detailed lipid profiling was performed using a VAP cholesterol test. CAD severity was categorized angiographically as no/minor CAD (<20% luminal diameter stenosis [LDS]), moderate CAD (20% to 74% LDS) and severe CAD (>75% LDS of any major coronary vessel). Results: Patients with severe CAD had significantly higher LDL₄ and triglycerides, and lower total HDL, HDL₂, HDL₃, LDL₂ and LDL₃ compared to patients with no/minor CAD (p <.05 for all). Multivariate analysis showed high LDL₄ as an independent predictive of severe CAD. ROC analysis showed an area under the curve of 0.62 (p <.0001) with a cut-point of >16.9 mg/dL to predict severe CAD with a sensitivity of 53% and specificity of 79%. Conclusion: Elevated LDL₄ levels are associated with severe CAD. Further large-scale investigations are required to evaluate the utility of LDL₄ in predicting CAD severity.