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 >16.9mg/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.