Development and Validation of Multiple Equations for Low-Density Lipoprotein and Apolipoprotein B in Korean Patients Visiting Local Clinics and Hospitals

Abstract

We investigated the utilization of apolipoprotein B (ApoB), an independent risk factor for cardiovascular disease, and developed and validated a translational equation for calculating low-density lipoprotein cholesterol (LDL-C) in the Korean population visiting local clinics and hospitals. Among a total of 469,520 data sets of the lipid profile panel (total cholesterol, triglycerides, and high-density lipoprotein cholesterols), 142,932 lipid test sets with data on LDL-C and/or ApoB were used for statistical analysis. Using linear regression analysis, we created ApoB percentile value-derived LDL-C equations in a creating set and validated them with previously reported equations (a total of 11 equations) in comparison to directly measured LDL-C using two independent validating sets. Among all lipid test sets, the simultaneously measured ApoB test only accounted for 2.0%, indicating its underutilization in Korea. The ApoB-derived equations, which were derived in this study and previous studies, showed an overall agreement of ≥94.3% for NCEP ATP III criteria. However, the accuracy of the equations varied among data sets of populations. Future studies are needed to validate translational equations for ApoB and LDL-C in different populations to clarify the clinical implications of these equations.

Exploring Utilization and Establishing Reference Intervals for the Apolipoprotein B Test in the Korean Population

“…There is a possibility that excluding healthy individuals with elevated cholesterol levels detected during routine preventative visits may have affected the reference intervals. However, considering that dyslipidemia is typically asymptomatic and the NCEP ATP III criteria are globally recognized for defining dyslipidemia, this study still holds value as an example of how to explore reference intervals in clinical laboratories with limited resources [2,21,22,30,[33][34][35][36]. In the present study, repeated measurements for the same individuals were excluded because the primary objective was to assess the reference intervals.…”

“…Because the aim of this study was to establish reference intervals for ApoB using data from individuals, repeated test results for the same individuals were excluded. After exclusion, laboratory test results were included only if they met the following criteria: TC < 240 mg/dL (non-hypercholesterolemia), TG < 200 mg/dL (non-hypertriglyceridemia), non-HDL-C < 190 mg/dL, and calculated LDL-C < 160 mg/dL using all three equations, including the Friedewald equation, Martin/Hopkins equation, and Sampson/NIH equation, according to the Criteria for the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria [2,21,22,30,[33][34][35][36]. The study population used to establish the reference intervals consisted of Koreans who had visited local clinics and hospitals for routine health check-ups and did not exhibit traditional lipid test abnormalities based on the NCEP ATP III criteria, which define subjects without dyslipidemia.…”

“…Various clinical guidelines offer distinct cutoff values for ApoB to identify individuals at risk and guide decision-making in management processes [3][4][5]. However, according to the current Korean guidelines for dyslipidemia, ApoB is recommended as an additional biomarker in specific clinical situations, such as diabetes and familial hypercholesterolemia, without specific cutoff values [21,22]. Clinicians should understand the use of specific cutoff values for ApoB with caution because the analytical method standardization for ApoB is not perfect [12,23].…”

Effect of Adding Apolipoprotein B Testing on the Prevalence of Dyslipidemia and Risk of Cardiovascular Disease in the Korean Adult Population

“…Traditional lipid tests, including TC, TG, HDL-C, and ApoB, were carried out using the Cholesterol Gen.2 (Roche, Mannheim, Germany), Triglyceride reagent without glycerol blank (Roche, Mannheim, Germany), HDL-Cholesterol plus 3rd generation kits, and the Tina-quant Apolipoprotein B ver.2 reagent kit (Roche, Mannheim, Germany), which is traceable to the IFCC reference material SP3-07. These tests were performed using automated Cobas 8000 system c702 analyzers (Roche, Mannheim, Germany) [ 18 , 20 ]. Non-HDL-C was calculated using the formula TC minus HDL-C. LDL-C was calculated using three equations suggested by Friedewald et al [ 21 ], Martin et al [ 22 ], and Sampson et al [ 23 ], referred to in this study as the Friedewald equation, the Martin/Hopkins equation, and the Sampson/NIH equation, respectively.…”