Comparison of direct and indirect measurement of LDL-C in HIV-infected individuals: ACTG 5087

Abstract

Background: Hypertriglyceridemia is common in HIV-infected individuals on antiretroviral therapy. Triglyceride (TG) levels >400 mg/dL interfere with the accurate determination of low-density lipoproteins (LDL-C) by the Friedewald equation, making it difficult to assess coronary heart disease risk.

Objective: The objective of this study is to compare the agreement of the direct LDL-C assay and the Friedewald equation with a reference ultracentrifugation method in the estimation of LDL-C concentrations.

Method: Samples from ACTG 5087 were assayed by ultracentrifugation and a direct enzymatic assay and calculated using the Friedewald equation.

Results: In subjects with TG <400 mg/dL (n = 271), 90% of the direct LDL-C values and Friedewald calculations were within 30 mg/dL and 32 mg/dL of the ultracentrifugation values, respectively. With TG > or = 400 mg/dL (n = 186), 90% of the direct assay and Friedewald observations were within 68 mg/dL and 120 mg/dL of the ultracentrifugation results, respectively. Only 27% of the LDL-C values were within 15 mg/dL of the ultracentrifugation LDL-C results for direct assay and 16.3% for the Friedewald equation.

Conclusion: The direct LDL-C assay and the calculated LDL-C values did not display adequate agreement with the reference ultracentrifugation method. In subjects with TG >400 mg/dL, the direct assay overestimates the actual LDL-C whereas the Friedewald calculation underestimates the actual LDL. Clinical usage of these methods may lead to misclassification of the severity of dyslipidemia, resulting in improper management.

Figures

Figure 1

Plots of LDL-C measurement error levels when comparing standard ultracentifugation method to (A) direct assay and (B) Friedewald calculation methods. Y-axis indicates the absolute difference in assay methods where ultracentrifugation is the standard. For example, zero would mean that standard assay agrees with alternate method. Horizontal dashed lines above and below zero indicate ±15 mg/dL.