Measuring Low Density Lipoprotein Cholesterol: Comparison of Direct Measurement by HiSens Reagents and Friedewald Estimation

Abstract

BackgroundDirectly measured low density lipoprotein cholesterol (DLDLC) has been reported to be more accurate than calculated low density lipoprotein cholesterol (CLDLC) using the Friedewald equation. However, some limitations of DLDLC have been reported. In this study, we evaluated differences between CLDLC and DLDLC measured using HiSens reagents.MethodsData were collected from 582 persons undergoing routine physical examinations at a general hospital. LDLC measurements were made directly or estimated using the Friedewald formula, and were classified according to the National Cholesterol Education Program's Adult Treatment Panel III guidelines. The relationship between these differences and other clinically relevant factors, such as triglyceride (TG) levels, were examined using multiple logistic regression analysis.ResultsThe DLDLC and CLDLC were strongly correlated according to simple linear regression analysis (r=0.917, P<0.001) but the mean difference between measurements was -11.0±15.3 (-62 to 90.5) mg/dL (P<0.001). For more than 10 mg/dL of their absolute differences, the DLDLC was typically lower than the CLDLC. The highest discrepancies in LDLC measurements occurred when LDLC was more than 160 mg/dL and less than 190 mg/dL. Differences in LDLC measurements were prone to striking negative and positive biases dependent on CLDLC and TG concentrations, respectively (all r>0.5).ConclusionUnlike other studies, DLDLC was significantly lower than CLDLC and the large differences in LDLC concentrations were not dependent on TG concentration. Our work suggests that verification of DLDLC accuracy is needed and differences in LDLC measurements should be accounted for in making clinical decisions.

Concordance between low density lipoprotein cholesterol concentration measurement by enzymatic method and calculation by Friedewald formula in cardiovascular risk classification

“…Many studies, using a variety of statistical techniques as been reported. 14,15 The level of agreement of the Lin's concordance correlation coefficient was moderate, but the two methods were not in satisfactory agreement. According to previous studies, calculations of LDL-C based on the Friedewald equation correlated well with direct measurement of LDL-C, almost, calculated LDL-C was underestimated in comparison to measured LDL-C. 16,17 Pearson's correlation coefficient should not be used as the sole criterion for determining the equivalence of methods.…”

Correlation of Friedewald′s calculated low-density lipoprotein cholesterol levels with direct low-density lipoprotein cholesterol levels in a tertiary care hospital

“…observed LDL cholesterol measured by direct LDL method was significantly lower than Friedewalds calculated LDL and differences in the LDL cholesterol concentrations had no relation with TG concentrations. [ 39 ] Gasko observed Anandaraja's calculated LDL correlated better than Friedewalds calculated LDL with direct LDL in a Brazilian population. [ 40 ] Nakanishi et al .…”

Requirement for Appropriate Methodology to Evaluate the Clinical Relevance of the Difference in Low-Density Lipoprotein Cholesterol Concentrations Obtained by Different Methods

“…We read with great interest the original article titled, “Measuring low density lipoprotein cholesterol: comparison of direct measurement by HiSens Reagents and Friedewald Estimation” by Lee et al 1) The authors compared two methods of low-density lipoprotein cholesterol (LDLC) measurement—direct estimation and indirect calculation (Friedewald formula) 2) —and further explored variables that might potentially influence the difference in LDLC levels obtained by these methods. However, we believe that certain concerns about their methodology warrant further discussion.…”

“…The authors compared the two methods using the following approaches: two sample paired t-test, Pearson's correlation, and percentage of concordance in the National Cholesterol Education Program's Adult Treatment Panel III categories. 1) These approaches, though appealing, are flawed and inappropriate for reasons long recognized. 3 4) Inferences based on whether the means of observations obtained by the two methods were ‘significantly different’ or not (using t-test) provide little information about the accuracy of the methods (which the authors wished to investigate).…”