Key points are not available for this paper at this time.
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: eS\, LDL-C= TC1. 15-HDL-C1. 25-TG6. 99- (TG NonHDL-C) 1120+TG^{2}8910+ (TG ApoB) 1240+ApoB4. 54-4. 73 e S L D L - C = TC 1. 15 - H D L - C 1. 25 - TG 6. 99 - T G × N o n H D L - C 1120 + TG 2 8910 + T G × A p o B 1240 + ApoB 4. 54 - 4. 73 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.
Coverdell et al. (Thu,) studied this question.