Low-Density Lipoprotein Particle Concentration and Size as Determined by Nuclear Magnetic Resonance Spectroscopy as Predictors of Cardiovascular Disease in Women

Abstract

Background-Nuclear magnetic resonance (NMR) offers an alternative, spectroscopic means of quantifying LDL and of measuring LDL particle size. Methods and Results-We conducted a prospective nested case-control study among healthy middle-aged women to assess LDL particle size (NMR) and concentration (NMR) as risk factors for future myocardial infarction, stroke, or death of coronary heart disease. Median baseline levels of LDL particle concentration (NMR) were higher (1597 vs 1404 nmol/L; Pϭ0.0001) and LDL particle size (NMR) was lower (21.5 vs 21.8 nm; Pϭ0.046) among women who subsequently had cardiovascular events (nϭ130) than among those who did not (nϭ130). Of these 2 factors, LDL particle concentration (NMR) was the stronger predictor (relative risk for the highest compared with the lowest quartileϭ4.17, 95% CI 1. 96 -8.87). This compared with a relative risk of 3.11 (95% CI 1.55-6.26) for the ratio of total cholesterol to HDL cholesterol and a relative risk of 5.91 (95% CI 2.65-13.15) for C-reactive protein.The areas under the receiver operating characteristic curves for LDL particle concentration (NMR), total cholesterol to HDL cholesterol ratio, and C-reactive protein were 0.64, 0.64, and 0.66, respectively. LDL particle concentration (NMR) correlated with several traditionally assessed lipid and nonlipid risk factors, and thus adjustment for these tended to attenuate the magnitude of association between LDL particle concentration (NMR) and risk. Conclusions-In this cohort, LDL particle concentration measured by NMR spectroscopy was a predictor of future cardiovascular risk. However, the magnitude of predictive value of LDL particle concentration (NMR) was not substantively different from that of the total cholesterol to HDL cholesterol ratio and was less than that of C-reactive protein.

Nano ES GEMMA and PDMA, new tools for the analysis of nanobioparticles—Protein complexes, lipoparticles, and viruses

“…LDL particles contain 10% triacylglycerines, 20% proteins, 20% phospholipids, and 40% cholesterinesters, and functions as a fast accessible cholesterin reservoir. From medical studies, it is known that its average size and blood level are possible predictors for cardiovascu- lar disease [23] (better than the cholesterol concentration contained within the LDL particles) and that the abundance of a small, dense subfraction are an indicator for arthrogenic dyslipidemia [31]. The GEMMA analysis shows, compared with VLDL, a narrow size distribution with an average size of 21.7 nm, which also corresponds well with data (22 nm) from literature [4,23].…”

“…From medical studies, it is known that its average size and blood level are possible predictors for cardiovascu- lar disease [23] (better than the cholesterol concentration contained within the LDL particles) and that the abundance of a small, dense subfraction are an indicator for arthrogenic dyslipidemia [31]. The GEMMA analysis shows, compared with VLDL, a narrow size distribution with an average size of 21.7 nm, which also corresponds well with data (22 nm) from literature [4,23]. HDL is the densest lipoparticle due to the highest percentage of proteins and smallest in size containing 50% proteins, 25% phospholipids, and 15% cholesterinesters.…”

“…This functional biocomplex is of particular interest because it consists not only of different proteins (heterocomplex) but contains also a huge amount of lipid molecules, namely triglycerides, cholesterol and its ester, and phospholipids. The analysis of blood concentration as well as size distribution [19 -22] of these lipoparticles is of great diagnostically importance for assigning the risk of cardiovascular and other lipid-connected health risks [23]. A recently granted U.S. patent indicates the use of GEMMA for a medical application in this field [24], and a brief mention was also given in a recent review article by Kaddis and Loo [8].…”

“…A recently granted U.S. patent indicates the use of GEMMA for a medical application in this field [24], and a brief mention was also given in a recent review article by Kaddis and Loo [8]. Furthermore, many subfractions of these particles (e.g., IDL or chylomicrons) were identified by analytical techniques such as NMR spectroscopy, gel electrophoresis, and vertical auto-profiling (ultracentrifugation), which allow the quantification of the various lipoparticles as a function of their size [23]. In the last application, the analysis and sampling of cylindrical (approximately 300 (length) ϫ 18 -20 nm (o.d.)…”

Fenofibrate Therapy Ameliorates Fasting and Postprandial Lipoproteinemia, Oxidative Stress, and the Inflammatory Response in Subjects With Hypertriglyceridemia and the Metabolic Syndrome

“…Elevated LDL particle levels identifies individuals at highest risk for atherosclerotic vascular disease (19) and cardiovascular events (20,21). In the VA-HIT study, high levels of LDL particles and low levels of HDL particles were independent predictors of new coronary heart disease (CHD) events (16).…”