Abstract
BACKGROUND: The accurate measurement of Low-density lipoprotein cholesterol (LDL-C) is critical in the decision to utilize the new lipid-lowering therapies like PCSK9-inhibitors (PCSK9i) for high-risk cardiovascular disease patients that do not achieve sufficiently low LDL-C on statin therapy. OBJECTIVE: To improve the estimation of low LDL-C by developing a new equation that includes apolipoprotein B (apoB) as an independent variable, along with the standard lipid panel test results. METHODS: Using β-quantification (BQ) as the reference method, which was performed on a large dyslipidemic population (N = 24,406), the following enhanced Sampson-NIH equation (eS LDL-C) was developed by least-square regression analysis: [Formula: see text] RESULTS: The eS LDL-C equation was the most accurate equation for a broad range of LDL-C values based on regression related parameters and the mean absolute difference (mg/dL) from the BQ reference method (eS LDL-C: 4.51, Sampson-NIH equation [S LDL-C]: 6.07; extended Martin equation [eM LDL-C]: 6.64; Friedewald equation [F LDL-C]: 8.3). It also had the best area-under-the-curve accuracy score by Regression Error Characteristic plots for LDL-C < 100 mg/dL (eS LDL-C: 0.953; S LDL-C: 0.920; eM LDL-C: 0.915; F LDL-C: 0.874) and was the best equation for categorizing patients as being below or above the 70 mg/dL LDL-C treatment threshold for adding new lipid-lowering drugs by kappa score analysis when compared to BQ LDL-C for TG < 800 mg/dL (eS LDL-C: 0.870 (0.853-0.887); S LDL-C:0.763 (0.749-0.776); eM LDL-C:0.706 (0.690-0.722); F LDL-C:0.687 (0.672-0.701). Approximately a third of patients with an F LDL-C < 70 mg/dL had falsely low test results, but about 80% were correctly reclassified as higher (≥ 70 mg/dL) by the eS LDL-C equation, making them potentially eligible for PCSK9i treatment. The M LDL-C and S LDL-C equations had less false low results below 70 mg/dL than the F LDL-C equation but reclassification by the eS LDL-C equation still also increased the net number of patients correctly classified. CONCLUSIONS: The use of the eS LDL-C equation as a confirmatory test improves the identification of high-risk cardiovascular disease patients, who could benefit from new lipid-lowering therapies but have falsely low LDL-C, as determined by the standard LDL-C equations used in current practice.