Ten-year evaluation of homogeneous low-density lipoprotein cholesterol methods developed by japanese manufacturers, application of the centers for disease control and prevention/cholesterol reference method laboratory network lipid standardization protocol

Aim: The risk index for atherosclerotic cardiovascular diseases in the Japanese metabolic syndrome-focused health checkup program was changed from total cholesterol (TC) to low-density lipoprotein cholesterol (LDL-C). We discuss the validity of this change with respect to standardization. Methods: The beta-quantification procedure of the Centers for Disease Control and Prevention (CDC) uses the LDL-C reference value as a target. Clinical laboratories and commercial manufacturers use homogeneous LDL-C methods for standardization. (A) For clinical laboratories, LDL-C in 648 samples requested from 108 hospitals was analyzed. (B) Manufacturers participated in the CDC/ Cholesterol Reference Method Laboratory Network LDL-C standardization protocol. The standardization was conducted with a performance follow-up for the 10-year period from 1998 to 2008 at 2-year intervals, 6 times. Results: (A) In clinical laboratories, acceptable LDL-C levels within ± 4% of the CDC s criteria remained 70.4%, 456 of 648 subjects. Negative maximum bias deviating from the LDL-C target value was - 35.8%, - 52.5 mg/dL, and positive maximum bias was + 24.5%, + 32.3 mg/dL. (B) For manufacturers, the standardization achievement rate of the analytical reagent/instrument/calibrator system in the last four standardizations from 2002 to 2008 remained on average 66.6%, far lower than the level required. Conclusions: The standardization achievement rate of homogeneous LDL-C methods was much lower than that of TC. TC should still be used as a risk index for atherosclerotic cardiovascular diseases. The standardization achievement rate of homogeneous LDL-C should be maintained at 100%, at least using samples with normal lipoprotein profiles. The accuracy and specificity of LDL-C should be further improved before practical and clinical use.