Association of Apolipoprotein B and Nuclear Magnetic Resonance Spectroscopy-Derived LDL Particle Number With Outcomes in 25 Clinical Studies: Assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on Best Practices

Study Questions:

Are either of the new methods for assessing cardiovascular disease risk, of apolipoprotein B (apo B) or indirectly by nuclear magnetic resonance (NMR) spectroscopy of serum low-density lipoprotein particle number (LDL-P), superior for predicting cardiovascular disease (CVD) events?


The number of circulating LDL particles is a strong indicator of future CVD events, and has consistently been shown to be superior to LDL cholesterol. Atherogenic (primarily LDL) particle number is typically determined either directly by the serum concentration of apo B or indirectly by NMR spectroscopy of serum LDL-P. The authors thus assessed the comparability of apo B and LDL-P. A total of 25 clinical studies containing 85 outcomes were reviewed. All studies measured both biomarkers.


In 21 of 25 (84.0%) studies, both apo B and LDL-P were significant for at least one CVD outcome. Neither was significant for any outcome in only one study (4.0%). In 50 of 85 comparisons (58.8%), both apo B and LDL-P had statistically significant associations with the clinical outcome, whereas in 17 comparisons (20.0%), neither was significantly associated with the outcome. In 18 comparisons (21.1%), there was discordance between apo B and LDL-P.


The authors concluded that in most studies, both apo B and LDL-P were comparable for predicting clinical outcomes, with nearly equivalent ability to assess risk for CVD. Currently, in the opinion of this Working Group on Best Practices, apo B appears to be the preferable biomarker for guideline adoption because of its availability, scalability, standardization, and relatively low cost.


This comprehensive and well-done meta-analysis of trials comparing the calculation of LDL with direct measures of particle number by measurement of apoB or NMR, indicated the superiority of these latter methods. Yet to be defined is the optimal way for clinicians to implement this testing. One limitation was the failure to compare with non&endash;high-density lipoprotein cholesterol, which has also been shown to be superior to LDL measurement alone. Nonetheless, this is an important issue that is thought to be one of the reasons for the delays seen in the publication of the Adult Treatment Panel 4 document. This is an issue for which clinicians should become familiar.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Lipid Metabolism, Nonstatins

Keywords: Biological Markers, Cholesterol, LDL, Cholesterol, HDL, Risk Assessment, Magnetic Resonance Spectroscopy

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