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

Abstract

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.

Keywords:

• Coronary artery disease
• LDL subtypes
• LDL4
• cholesterol

Transparency

Declaration of funding

This manuscript did not receive any funding.

Declaration of financial/other relationships

P.A.G. has disclosed that he has served as a consultant for Daiichi Sankyo/Lilly, Bayer, AstraZeneca, Accumetrics, Merck, Medtronic, Janssen, CSL, and Haemonetics; received grants from the National Institutes of Health, Daiichi Sankyo, Lilly, CSL, AstraZeneca, Haemonetics, Harvard Clinical Research Institute, and Duke Clinical Research Institute; received payment for lectures, including service on speakers’ bureaus, from Lilly, Daiichi Sankyo, and Merck; received payment for development of educational presentations from Merck, the Discovery Channel, and Pri-Med; holds stock or stock options in Merck, Medtronic, and Pfizer; and holds patents in the area of personalized antiplatelet therapy and interventional cardiology. P.P.T. has disclosed that he has served in speakers’ bureaus for Amarin, Amgen, Kowa, Merck, Regeneron, Sanofi-Aventis; and serves as a consultant for Amgen, AstraZeneca, Kowa, Merck and Regeneron. R.C., D.M., K.B., U.S.T., T.S., M.G.G., C.J.F. and S.P. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

The authors wish to acknowledge our research coordinators, Tania Gesheff RN MSN, Kiran Kalra MBBS, and Cescelle Barbour RN MSN, for their contributions to the study. The authors also acknowledge Ms. Abby Jones for her skillful technical assistance in testing the samples.