Development and validation of a hydrogen-1 NMR method for lipoprotein quantification and coronary heart disease risk assessment.

摘要

There is abundant evidence that the subclasses within a given lipoprotein class differ in their associations with coronary heart disease. Since subclass distributions can vary widely from person to person, individuals with the same levels of LDL cholesterol and HDL cholesterol may be at different cardiovascular risk and respond differently to dietary and drug therapy. Unfortunately, existing laboratory methods of subclass measurement are too time-consuming and expensive to be used in routine clinical practice. Using a new approach to lipoprotein analysis that exploits the natural proton NMR spectroscopic differences exhibited by lipoprotein particles of different size, we have developed a new quantitative NMR technology for use in clinical laboratory medicine. The newly developed NMR LipoProfile assay rapidly and simultaneously quantifies the lipoprotein subclass particle concentrations of 10 lipoprotein species (3 VLDL, IDL, 3 LDL and 3 HDL) with good intraassay and interassay precision. Extensive validation studies were conducted that established robustness of the NMR lipoprotein particle assay. The average particle sizes of the major lipoprotein classes determined by NMR correlate very well with those estimated by gradient gel electrophoresis. Emerging clinical data from several coronary disease outcome studies indicate that NMR-derived lipoprotein particle parameters are superior predictors of cardiovascular disease risk compared to traditional cholesterol risk factors. The speed and efficiency of NMR lipoprotein subclass profiling make it a potentially valuable research tool and cost-effective means of assessing and managing heart disease risk in the general population.