Analytical and Clinical Evaluation of Two Homogeneous Assays for LDL-cholesterol in Hyperlipidemic Patients

Background: LDL-cholesterol (LDL-C) concentrations are the primary basis for treatment guidelines established for hyperlipidemic patients. LDL-C concentrations are commonly monitored by means of the Friedewald formula, which provides a relative estimation of LDL-C concentration when the triglyceride concentration is <2000 mg/L and there are no abnormal lipids. The Friedewald formula has several limitations and may not meet the current total error requirement of <12% in LDL-C measurements.

Methods: We evaluated the analytical and clinical performance of two direct methods (Roche and Wako) by analyzing 313 fresh serum samples obtained from dyslipidemic patients in a lipid clinic and comparing them with modified beta-quantification.

Results: Both homogeneous assays displayed excellent precision (CV <2%). The Roche method showed a mean total error of 7.72%, and the Wako method showed a mean total error of 4.46% over a wide range of LDL-C concentrations. The Roche method correlated highly with the modified beta-quantification assay (r = 0.929; y = 1.052x - 168 mg/L; n = 166) and showed a bias of -4. 5% as a result of the assigned standard value. The Wako method also correlated highly with beta-quantification (r = 0.966; y = 0.9125x + 104.8 mg/L; n = 145) without significant bias. The Roche method correctly classified 97% of patients with triglycerides <2000 mg/L, 75% of patients with type IIb hyperlipemia (HPL), and 84% of patients with type IV HPL based on the cutpoints of 1300 and 1600 mg/L, compared with 98%, 78.4%, and 89%, respectively, for the Wako method. In dysbetalipoproteinemic patients, both methods have a 30% mean positive bias compared with beta-quantification.

Conclusions: Both direct methods can be a useful alternative when ultracentrifugation is not available for the diagnosis and control of lipid-lowering medication for patients with mixed HPL, but not for patients with type III hyperlipidemia.