Validity of the Conventional Indirect Methods Including Friedewald Method for Determining Serum Low‐Density Lipoprotein Cholesterol Level: Comparison with the Direct Homogeneous Enzymatic Analysis

Abstract

Validity of the Conventional Indirect Methods Including Friedewald Method for Determining Serum Low-Density Lipoprotein Cholesterol Level: Comparison with the Direct Homogeneous Enzymatic Analysis: Noriyuki Nakanishi, et al. Department of Social and Environmental Medicine, Course of Social Medicine, Osaka University Graduate School of Medicine F2—Low-density lipoprotein cholesterol (LDLC) concentrations are most commonly estimated by the Friedewald formula [LDLC=total cholesterol (TC) - high-density lipoprotein cholesterol - triglycerides (TG)/5]. To assess the validity of the conventional indirect methods including Friedewald method for determining serum LDLC level, we analyzed 1953 serum samples from Japanese male office workers and compared the measured (the direct N-geneous assay) serum LDLC concentrations with calculated values, by using several terms for TG (i.e., TG/4, TG/4.5, TG/5, TG/5.5, TG/6, TG/7, and TG/8) in the Friedewald formula. Linear regression analyses showed the highest correlation for the estimated LDLC by the original Friedewald formula, with the term TG/5, with the measured LDLC (r=0.958). The mean LDLC estimated by means of the original Friedewald formula was 1.4 mg/d/ higher than the mean measured LDLC (p<0.001), but the difference between the mean estimated LDLC and the mean measured LDLC was the smallest for estimation by means of the original Friedewald formula. As for the accuracy of calculation methods, TG/5 agreed best with the direct assay for TG concentrations ≤99 mg/d/and TG/4.5 was best for TG concentrations of 100-249 mg/d/. For TG concentrations ≥250 mg/d/, TG/5 most closely matched the measured LDLC and gave the smallest mean percent errors, but with increasingly large estimation errors as TG increased. As for the accuracy of calculation methods according to lipidemic type, TG/5 was the best estimating term for normolipidemics (TC ≤219 mg/d/ and TG ≤149 mg/d/) and hypertriglyceridemics (TC ≤ 219 mg/d/and TG ≥ 150 mg/ 61), but the percentages of samples correctly estimated decreased with increasing TG concentrations. These results suggest that the original Friedewald formula, with the term TG/5, is reasonably well classified at TG concentrations ≤99 mg/d/ or in normolipidemics, but the potential for significant estimation errors steadily increases with increasing TG concentrations. We conclude that direct LDLC assay such as the N-geneous method is a useful tool in the diagnosis and management of hypercholesterolemics, especially for those with increased TG.