scholarly journals 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

2013 ◽  
Vol 59 (5) ◽  
pp. 752-770 ◽  
Author(s):  
Thomas G Cole ◽  
John H Contois ◽  
Gyorgy Csako ◽  
Joseph P McConnell ◽  
Alan T Remaley ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Best Practices ◽  
Clinical Studies ◽  
Apolipoprotein B ◽  
Working Group ◽  
Particle Number ◽  
Apo B ◽  
Ldl Particles ◽  
Nuclear Magnetic

BACKGROUND The number of circulating LDL particles is a strong indicator of future cardiovascular disease (CVD) events, even superior to the concentration of LDL cholesterol. Atherogenic (primarily LDL) particle number is typically determined either directly by the serum concentration of apolipoprotein B (apo B) or indirectly by nuclear magnetic resonance (NMR) spectroscopy of serum to obtain NMR-derived LDL particle number (LDL-P). CONTENT To assess the comparability of apo B and LDL-P, we reviewed 25 clinical studies containing 85 outcomes for which both biomarkers were determined. In 21 of 25 (84.0%) studies, both apo B and LDL-P were significant for at least 1 outcome. Neither was significant for any outcome in only 1 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. CONCLUSIONS In most studies, both apo B and LDL-P were comparable in association with clinical outcomes. The biomarkers were nearly equivalent in their ability to assess risk for CVD and both have consistently been shown to be stronger risk factors than LDL-C. We support the adoption of apo B and/or LDL-P as indicators of atherogenic particle numbers into CVD risk screening and treatment guidelines. 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.

scholarly journals The extended lipid panel assay: a clinically-deployed high-throughput nuclear magnetic resonance method for the simultaneous measurement of lipids and Apolipoprotein B

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Erwin Garcia ◽  
Dennis W. Bennett ◽  
Margery A. Connelly ◽  
Elias J. Jeyarajah ◽  
Franklin C. Warf ◽  
...  
Keyword(s):  
Decision Making ◽  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
High Throughput ◽  
Apolipoprotein B ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Panel ◽  
Compositional Diversity ◽  
Nuclear Magnetic

Abstract Background Standard lipid panel assays employing chemical/enzymatic methods measure total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C), from which are calculated estimates of low-density lipoprotein cholesterol (LDL-C). These lipid measures are used universally to guide management of atherosclerotic cardiovascular disease risk. Apolipoprotein B (apoB) is generally acknowledged to be superior to LDL-C for lipid-lowering therapeutic decision-making, but apoB immunoassays are performed relatively infrequently due to the added analytic cost. The aim of this study was to develop and validate the performance of a rapid, high-throughput, reagent-less assay producing an “Extended Lipid Panel” (ELP) that includes apoB, using the Vantera® nuclear magnetic resonance (NMR) analyzer platform already deployed clinically for lipoprotein particle and other testing. Methods Partial least squares regression models, using as input a defined region of proton NMR spectra of plasma or serum, were created to simultaneously quantify TC, TG, HDL-C, and apoB. Large training sets (n > ~ 1000) of patient sera analyzed independently for lipids and apoB by chemical methods were employed to ensure prediction models reflect the wide lipid compositional diversity of the population. The analytical performance of the NMR ELP assay was comprehensively evaluated. Results Excellent agreement was demonstrated between chemically-measured and ELP assay values of TC, TG, HDL-C and apoB with correlation coefficients ranging from 0.980 to 0.997. Within-run precision studies measured using low, medium, and high level serum pools gave coefficients of variation for the 4 analytes ranging from 1.0 to 3.8% for the low, 1.0 to 1.7% for the medium, and 0.9 to 1.3% for the high pools. Corresponding values for within-lab precision over 20 days were 1.4 to 3.6%, 1.2 to 2.3%, and 1.0 to 1.9%, respectively. Independent testing at three sites over 5 days produced highly consistent assay results. No major interference was observed from 38 endogenous or exogenous substances tested. Conclusions Extensive assay performance evaluations validate that the NMR ELP assay is efficient, robust, and substantially equivalent to standard chemistry assays for the clinical measurement of lipids and apoB. Routine reporting of apoB alongside standard lipid measures could facilitate more widespread utilization of apoB for clinical decision-making.

scholarly journals Estimation of LDL-Associated Apolipoprotein B from Measurements of Triglycerides and Total Apolipoprotein B

2008 ◽  
Vol 54 (5) ◽  
pp. 907-910 ◽  
Author(s):  
Arthur M Baca ◽  
G Russell Warnick
Keyword(s):  
Apolipoprotein B ◽  
Particle Number ◽  
Strongly Correlated ◽  
Apo B ◽  
B Values ◽  
Ldl Particles ◽  
Convenient Means ◽  
Subsequent Measurement ◽  
Simple Linear Equation ◽  
Fraction Density

Abstract Background: VLDL and chylomicrons may interfere with measurements of apolipoprotein B (apo B) on LDL particles. Ultracentrifugation of samples enriched in chylomicrons and VLDL and subsequent measurement of apo B in the infranate fraction [density (d) = 1.006] removes this interference. This apo B fraction is called “LDL–apo B.” Methods: We retrospectively analyzed 64 895 measurements of triglycerides, total apo B, and LDL–apo B. Samples were ultracentrifuged, and 3 commercially available immunoassays that use different antibodies were used to measure LDL–apo B in the 1.006 infranate fraction. Results: After adjusting for triglyceride concentration, we found total apo B and LDL–apo B measurements to be strongly correlated. We derived a simple linear equation for calculating LDL–apo B concentration (in milligrams per deciliter) from measurements of total apo B and triglycerides: LDL–apo B = apo B − 10 mg/dL − triglycerides/32. This equation accurately predicts LDL–apo B values within ±12% of the measured value in 75% of cases. Conclusions: Our equation provides a convenient means of estimating LDL–apo B from commonly available measurements of total apo B and triglycerides without the need for ultracentrifugation. LDL–apo B measurements were also independent of the different apo B antibodies in the 3 assays used in this study. An equation that predicts LDL–apo B particle number may be useful, regardless of the apo B assay used.

scholarly journals The Extended Lipid Panel Assay: A Clinically-Deployed High-Throughput Nuclear Magnetic Resonance Method for the Simultaneous Measurement of Lipids and Apolipoprotein B

2020 ◽  
Author(s):  
Erwin Garcia ◽  
Dennis W. Bennett ◽  
Margery A. Connelly ◽  
Elias J. Jeyarajah ◽  
Franklin C. Warf ◽  
...  
Keyword(s):  
Decision Making ◽  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
High Throughput ◽  
Apolipoprotein B ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Lipid Panel ◽  
Compositional Diversity ◽  
Nuclear Magnetic

Abstract BackgroundStandard lipid panel assays employing chemical/enzymatic methods measure total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C), from which are calculated estimates of low-density lipoprotein cholesterol (LDL-C). These lipid measures are used universally to guide management of atherosclerotic cardiovascular disease risk. Apolipoprotein B (apoB) is generally acknowledged to be superior to LDL-C for lipid-lowering therapeutic decision-making, but apoB immunoassays are performed relatively infrequently due to the added analytic cost. The aim of this study was to develop and validate the performance of a rapid, high-throughput, reagent-less assay producing an “Extended Lipid Panel” (ELP) that includes apoB, using the Vantera® nuclear magnetic resonance (NMR) analyzer platform already deployed clinically for lipoprotein particle and other testing.MethodsPartial least squares regression models, using as input a defined region of proton NMR spectra of plasma or serum, were created to simultaneously quantify TC, TG, HDL-C, and apoB. Large training sets (n >~1,000) of patient sera analyzed independently for lipids and apoB by chemical methods were employed to ensure prediction models reflect the wide lipid compositional diversity of the population. The analytical performance of the NMR ELP assay was comprehensively evaluated.ResultsExcellent agreement was demonstrated between chemically-measured and ELP assay values of TC, TG, HDL-C and apoB with correlation coefficients ranging from 0.980 to 0.997. Within-run precision studies measured using low, medium, and high level serum pools gave coefficients of variation for the 4 analytes ranging from 1.0 to 3.8% for the low, 1.0 to 1.7% for the medium, and 0.9 to 1.3% for the high pools. Corresponding values for within-lab precision over 20 days were 1.4 to 3.6%, 1.2 to 2.3%, and 1.0 to 1.9%, respectively. Independent testing at three sites over 5 days produced highly consistent assay results. No major interference was observed from 38 endogenous or exogenous substances tested.ConclusionsExtensive assay performance evaluations validate that the NMR ELP assay is efficient, robust, and substantially equivalent to standard chemistry assays for the clinical measurement of lipids and apoB. Routine reporting of apoB alongside standard lipid measures could facilitate more widespread utilization of apoB for clinical decision-making.

scholarly journals Physicochemical Properties of Lipoproteins Assessed by Nuclear Magnetic Resonance as a Predictor of Premature Cardiovascular Disease. PRESARV-SEA Study

2021 ◽  
Vol 10 (7) ◽  
pp. 1379
Author(s):  
Bárbara Fernández-Cidón ◽  
Beatriz Candás-Estébanez ◽  
Miriam Gil-Serret ◽  
Núria Amigó ◽  
Emili Corbella ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Physicochemical Properties ◽  
Lipid Profile ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Ldl Particles ◽  
Premature Cardiovascular Disease ◽  
Nuclear Magnetic

Some lipoprotein disorders related to the residual risk of premature cardiovascular disease (PCVD) are not detected by the conventional lipid profile. In this case-control study, the predictive power of PCVD of serum sdLDL-C, measured using a lipoprotein precipitation method, and of the physicochemical properties of serum lipoproteins, analyzed by nuclear magnetic resonance (NMR) techniques, were evaluated. We studied a group of patients with a first PCVD event (n = 125) and a group of control subjects (n = 190). Conventional lipid profile, the size and number of Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL), High Density Lipoproteins (HDL) particles, and the number of particles of their subclasses (large, medium, and small) were measured. Compared to controls, PCVD patients had lower concentrations of all LDL particles, and smaller and larger diameter of LDL and HDL particles, respectively. PCVD patients also showed higher concentrations of small dense LDL-cholesterol (sdLDL), and triglycerides (Tg) in LDL and HDL particles (HDL-Tg), and higher concentrations of large VLDL particles. Multivariate logistic regression showed that sdLDL-C, HDL-Tg, and large concentrations of LDL particles were the most powerful predictors of PCVD. A strong relationship was observed between increased HDL-Tg concentrations and PCVD. This study demonstrates that beyond the conventional lipid profile, PCVD patients have other atherogenic lipoprotein alterations that are detected by magnetic resonance imaging (MRI) analysis.

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