The proposed research is aimed at developing and evaluating the clinical utility of new methodology using H1 NMR spectroscopy to quantitate the levels of the constituent lipoproteins of human blood plasma (VLDL, LDL, HDL). The accurate identification of individuals at risk for coronary heart disease (CHD) is a high priority in the national effort to combat this disease. Markers of CHD risk that are in current widespread use for population screening have proven to be of great value in this effort. These include total cholesterol and triglyceride, LDL- and HDL- cholesterol, and apolipoproteins A-1 and B. Accurate measurement of these constituents is a prerequisite for their effective clinical use and continues to be a challenging problem. Our preliminary studies indicate that it is possible in a simple and rapid process to extract the concentrations of VLDL, LDL, and HDL present in an individual's blood from a computer lineshape analysis of the lipid resonances in a H1 NMR spectrum of the plasma. There are still a great number of questions remaining concerning the precise meaning of the data provided by the technique, its accuracy and reproducibility, and its possible clinical uses. The proposed research addresses these questions and has the following as its specific goals; 1) documentation of the NMR spectral relationships between the lipoprotein subspecies that comprise the three broad components (VLDL, LDL, HDL) used in the lineshape analysis, 2) determination of the extent to which variability in subspecies and lipid composition affect the lineshapes and amplitudes at a given temperature of the individual lipoprotein components, 3) optimization of the analytical protocol for NMR plasma lineshape analysis by documenting the influence of factors such as magnetic field strength, temperature, and fitting algorithm on the accuracy of the analysis, 4) determination of the relationships between NMR-derived lipoprotein levels and those provided by lipoprotein lipid and apolipoprotein assays, and 5) evaluation of the potential diagnostic utility of NMR-derived lipoprotein levels by determining their association with CHD as assessed by coronary arteriography.
