A comparative study of four independent methods to measure LDL particle concentration.

ABSTRACT

BACKGROUND: Low-density lipoprotein particle concentration (LDL-P) is generally more predictive of clinical cardiovascular endpoints than LDL cholesterol (LDL-C). Few studies have directly compared multiple LDL-P methods, particularly with ultracentrifugation. OBJECTIVE: Examine comparability and precision of 4 LDL-P methods. METHODS: We divided serum from 48 subjects into blinded triplicates and measured LDL-P in 3 separate laboratories by 4 methods: ultracentrifugation (reference method), a novel electrophoretic method, and nuclear magnetic resonance spectroscopy (NMR) by 2 independent methods: a 400 MHz Vantera(®) instrument supplied by Liposcience (LS-NMR) and operated at ARUP Laboratories, and a 600 MHz Bruker instrument (ASCEND 600) operated at Health Diagnostic Laboratory (HD-NMR). RESULTS: Of the 4 methods, ultracentrifugation was the most precise and LS-NMR the least; the latter had a significantly greater CV (p < 0.0001) as compared with all 3 of the other methods, although all CVs were clinically acceptable. The electrophoretic method showed similar precision to ultracentrifugation, while HD-NMR was intermediate. The HD-NMR had the slope closest to 1 (0.90, 95% CI 0.71 to 1.09) and the intercept closest to 0 (-48, -353 to 256) compared to the ultracentrifugation method in Deming regression models. While the two NMR methods correlated well (r = 0.95) with each other and had a slope equivalent to 1 (1.08, 0.98 to 1.19), their intercept in Deming regression excluded 0 (194, 53 to 335) indicating a vertical shift between the two methods. CONCLUSIONS: This LDL-P method comparison may prove useful for future research and clinical applications.