Seven Direct Methods for Measuring HDL and LDL Cholesterol Compared with Ultracentrifugation Reference Measurement Procedures

Abstract

BACKGROUND Methods from 7 manufacturers and 1 distributor for directly measuring HDL cholesterol (C) and LDL-C were evaluated for imprecision, trueness, total error, and specificity in nonfrozen serum samples. METHODS We performed each direct method according to the manufacturer’s instructions, using a Roche/Hitachi 917 analyzer, and compared the results with those obtained with reference measurement procedures for HDL-C and LDL-C. Imprecision was estimated for 35 runs performed with frozen pooled serum specimens and triplicate measurements on each individual sample. Sera from 37 individuals without disease and 138 with disease (primarily dyslipidemic and cardiovascular) were measured by each method. Trueness and total error were evaluated from the difference between the direct methods and reference measurement procedures. Specificity was evaluated from the dispersion in differences observed. RESULTS Imprecision data based on 4 frozen serum pools showed total CVs <3.7% for HDL-C and <4.4% for LDL-C. Bias for the nondiseased group ranged from −5.4% to 4.8% for HDL-C and from −6.8% to 1.1% for LDL-C, and for the diseased group from −8.6% to 8.8% for HDL-C and from −11.8% to 4.1% for LDL-C. Total error for the nondiseased group ranged from −13.4% to 13.6% for HDL-C and from −13.3% to 13.5% for LDL-C, and for the diseased group from −19.8% to 36.3% for HDL-C and from −26.6% to 31.9% for LDL-C. CONCLUSIONS Six of 8 HDL-C and 5 of 8 LDL-C direct methods met the National Cholesterol Education Program total error goals for nondiseased individuals. All the methods failed to meet these goals for diseased individuals, however, because of lack of specificity toward abnormal lipoproteins.

The Relationship Between Low-Density Lipoprotein Cholesterol Levels and the Incidence of Cardiovascular Disease in High-Risk Patients Treated With Pravastatin

“…Recently, it was reported that the Friedewald method is more appropriate for determining LDL-C values than direct methods, because of the great variability between different measuring kits. 40) However, we decided to adopt direct methods in this analysis because of the lack of a great number of total cholesterol values, which is related to the reimbursement policy in some regions. Many institutions were not allowed to measure both total cholesterol and LDL-C by direct methods during the study period.…”

Comparison of equations for the calculation of LDL-cholesterol in hospitalized patients

“…Furthermore, direct methods show poor performance with high triglyceride (TG) levels [4][5][6]. An earlier review comparing direct measurement of LDL-C vs calculation of LDL recommended the use of direct LDL measurements in hypertriglyceridaemic patients [6].…”

Ten-year evaluation of homogeneous low-density lipoprotein cholesterol methods developed by Japanese manufacturers

“…We also reported several discrepancies in LDL-C levels by the HPLC method and the CDC reference procedure using lipoprotein abnormalities, such as lipoprotein lipase deficiency, E2/2 type III hyperlipidemia, cholesteryl ester transfer protein deficiency and hyper Lp(a) lipoproteinemia 19) . In the US-Japan cooperative evaluation of current generations of homogeneous methods for measuring HDL and LDL cholesterol 20) , we have already investigated the analytical performance of seven LDL-C homogeneous assay kits using diseased (primarily dyslipidemic and cardiovascular) as well as the non-diseased individuals in the United States 20) . As expected, all the LDL-C assay methods failed to meet the goals for diseased individuals because of a lack of specificity for abnormal lipoproteins.…”