Abstract

Introduction: Despite more accurate low-density lipoprotein cholesterol (LDL-C) estimates by the Martin (mLDL-C) method, most laboratories still use the Friedewald (fLDL-C) equation. Low non-high density lipoprotein (non-HDL-C) and high triglycerides (TG) drive inaccuracy in LDL-C estimation. We compared a strategy of identifying errors in fLDL-C using non-HDL-C/TG ratios with subsequent reflex direct LDL-C testing to a strategy of using mLDL-C. Methods: We included 4,939,542 individuals (2/3 derivation, 1/3 validation dataset) with TG <400 mg/dL with lipid profiles directly measured via Vertical Auto Profile from the Very Large Database of Lipids. We compared directly measured LDL-C with estimated fLDL-C and mLDL-C. The direct LDL-C assay has an allowable error of 12% which was used as the threshold for accuracy assessment. LDL-C estimates above and below non-HDL-C/TG cutpoints (range 0-2.0) were evaluated for accuracy from the derivation dataset and the 4 best performing ratios were tested in the validation set. Individuals with non-HDL-C/TG ratios below the cutpoints were assumed to require direct LDL-C measurement. Medicare costs ($17 lipid panel; $12 direct LDL-C) were used to estimate added costs of direct LDL-C measurement. Results: Nearly 8% of fLDL-C results deviated >12% from direct LDL-C compared with only 2.5% of mLDL-C results in the entire population. Non-HDL-C/TG ratios of 0.6-0.9 performed best in the derivation dataset. In the validation dataset, a non-HDL-C/TG ratio of 0.7 had the highest area under the curve for identifying >12% error in fLDL-C estimates (Table). At this ratio, 14.5% of fLDL-C samples would need direct LDL-C measurement at an increase in costs of lipid testing by 10%. Conclusions: Use of non-HDL-C/TG ratio <0.7 as screening for direct LDL-C measurement can improve the accuracy of LDL-C estimates in labs using the Friedewald equation. However, such an approach is significantly costlier than using mLDL-C.

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