Discordance between apolipoprotein B and low-density lipoprotein particle number is associated with insulin resistance in clinical practice

BACKGROUND: Discordance between measures of atherogenic lipoprotein particle number (apolipoprotein B [ApoB] and low-density lipoprotein [LDL] particle number by nuclear magnetic resonance spectroscopy [LDL-PNMR]) is not well understood. Appropriate treatment considerations in such cases are unclear. OBJECTIVES: To assess discordance between apoB determined by immunoassay and LDL-PNMR in routine clinical practice, and to characterize biomarker profiles and other clinical characteristics of patients identified as discordant. METHODS: Two retrospective cohorts were evaluated. First, 412,013 patients with laboratory testing performed by Health Diagnostic Laboratory, Inc., as part of routine care; and second, 1411 consecutive patients presenting for risk assessment/reduction at 6 US outpatient clinics. Discordance was quantified as a percentile difference (LDL-PNMR percentile - apoB percentile) and attainment of percentile cutpoints (LDL-PNMR ≥ 1073 nmol/L or apoB ≥ 69 mg/dL). A wide range of cardiovascular risk factors were compared. RESULTS: ApoB and LDL-PNMR values were highly correlated (R(2) = 0.79), although substantial discordance was observed. Similar numbers of patients were identified as at-risk by LDL-PNMR when apoB levels were < 69 mg/dL (5%-6%) and by apoB values when LDL-PNMR was < 1073 nmol/L (6%-7%). Discordance (LDL-PNMR > apoB) was associated with insulin resistance, smaller LDL particle size, increased systemic inflammation, and low circulating levels of "traditional" lipids, whereas discordance (apoB > LDL-PNMR) was associated with larger LDL particle size, and elevated levels of lipoprotein(a) and lipoprotein-associated phospholipase A2 (Lp-PLA2). CONCLUSION: Discordance between apoB and LDL-PNMR in routine clinical practice is more widespread than currently recognized and may be associated with insulin resistance.