John H. Contois, PhD
Measurement of low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol is the cornerstone of cardiovascular disease risk assessment. Yet few of us appreciate the potential for error due to imprecision and inaccuracy. Despite the widespread belief that the calculation or measurement of LDL or HDL cholesterol is standardized and reproducible, the data indicate that results can vary significantly with methods from different manufacturers, and calculated LDL cholesterol may not agree with measured LDL cholesterol. Problems with direct HDL-C assays also raise concerns about the reliability of calculated LDL cholesterol and non-HDL cholesterol measurement. Poor reliability of these assays relate to the ambiguity in the definition of both LDL and
HDL particles, and the heterogeneity of LDL and HDL particles (1).
For clinical research organizations (CROs), contract laboratories, and academic and pharmaceutical research laboratories developing next generation lipid therapies and diagnostics, choice of methods is vitally important. Clinical laboratories, especially those that specialize in lipid testing, should also consider assay reliability when choosing methods. This manuscript examines the reliability of current methodologies for measurement of LDL and HDL cholesterol and suggests that “old school” methods, such as dextran sulfate precipitation, perform better than newer homogeneous assays.
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