The proposed research is aimed at continuing the development of a promising new analytical method that uses proton NMR spectroscopy to simultaneously quantify the concentrations of all of the major lipoproteins in plasma (chylomicrons, VLDL, LDL, HDL), plus determine their subspecies distributions. 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 in widespread use for population screening are those that can be measured relatively simply and inexpensively. These include total plasma cholesterol, triglyceride, and HDL- and LDL-cholesterol. Initial assignment of CHD risk is currently made on the basis of total cholesterol level; HDL- and LDL-cholesterol measurements are only recommended for those in the moderate and high risk groups: This stepwise approach has several deficiencies which stem from the significant analytical errors associated with laboratory cholesterol and lipoprotein measurements. The new NMR method of lipoprotein analysis has the advantage of supplying an individual's complete lipoprotein profile all at once, using a procedure that is fast, simple, and capable of being completely automated. The basic information is provided by a single proton NMR spectrum of nonfasting plasma, which is then subjected to computer lineshape analysis. Additional research is needed to optimize the methodology used to derive this information, explore the potential of extracting from the spectrum additional information of clinical relevance, and document the relationship of NMR-derived lipoprotein levels to those measured by standard methods. The specific objectives of the research are to 1) determine the best computational approach(es) to extracting the maximum amount of information about lipoprotein levels from the plasma NMR spectrum, 2) determine the maximum resolving power of the NMR method in terms of its ability to quantify lipoprotein subspecies and Lp(a), 3) determine the influence of lipoprotein lipid compositional heterogeneity on the accuracy of the analysis by investigating the thermal profiles of LDL and HDL subspecies of defined lipid and fatty acid composition, and 4) compare NMR-derived lipoprotein concentrations and subspecies distributions with those determined by other chemical and physical methods of analysis.
