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

Abstract

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.

Effect of Switching From Statin Monotherapy to Ezetimibe/Simvastatin Combination Therapy Compared With Other Intensified Lipid‐Lowering Strategies on Lipoprotein Subclasses in Diabetic Patients With Symptomatic Cardiovascular Disease

“…Additionally, differences in assessment of apoB with immunoassay [LDL, very low‐density lipoprotein, intermediate‐density lipoprotein, and lipoprotein(a)] and of LDL‐P with NMR [LDL subfractions, intermediate‐density lipoprotein, and lipoprotein(a)] may partly account for these discordant observations. In line with this, a review of 25 clinical trials showed that although apoB and LDL‐P were comparably associated with clinical outcomes in most studies, some discordance was noted, which was attributed to inherent methodological differences in measurement of these markers 51. Further studies are needed to better understand the relationship between apoB and LDL‐P, as well as assessment of these markers in various populations.…”

Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications

“…Lp-X formation is typically associated with a low apo B-100 concentration together with a high total cholesterol concentration [44] . The usual target level of apo B-100 is below 90 mg/dL, corresponding to a true LDL cholesterol concentration of below 3.0 mmol/L (116 mg/dL) [49][50][51] . The ratio of apo B-100 to total cholesterol is normally around 1:2, but may be 1:10 in cases of severe Lp-X formation [45] .…”

“…The ratio of apo B-100 to total cholesterol is normally around 1:2, but may be 1:10 in cases of severe Lp-X formation [45] . Since an elevated apo B-100 concentration is a risk factor for atherosclerosis [49][50][51] , apo B-100 concentrations should be measured when considering lipid-lowering treatment in PBC and other cholestatic conditions (Figure 4). Even when LDL cholesterol levels are high, cholesterol-lowering medication is unnecessary in cases where apo B-100 is below 90 mg/dL, since this suggests prevalence of non-atherogenic Lp-X.…”

Advanced lipoprotein testing for cardiovascular diseases risk assessment: a review of the novel approaches in lipoprotein profiling

“…After digestion, apolipoprotein-specific tryptic peptides were identified for each major class of apolipoproteins, and some of them were selected for quantification by ID/MS [60][61][62]. ID/MS quantification uses synthetic labeled entities with 13 C, 15 N or deuterium as internal standards (IS) to spike the samples. Depending on the method, this IS can be either the labeled recombinant protein or a synthetic labeled peptide characteristic of the protein.…”

“…In this search, the importance of lipoprotein particles themselves in the atherosclerosis pathway, rather than their lipid content, was evidenced and different biomarkers emerged. For instance, increased concentrations of lipoprotein(a) were found to be causally related to premature CVD [9][10][11][12], and a strong correlation between elevated concentrations of apolipoprotein B (apoB) and CVD risk was evidenced [13][14][15]. It has also been demonstrated that small-dense LDL (sd-LDL) particles tended to be more atherogenic and were associated with premature CVD events [16][17][18][19][20].…”