Comparison between gradient gel electrophoresis and nuclear magnetic resonance spectroscopy in estimating coronary heart disease risk associated with LDL and HDL particle size.

BACKGROUND Gradient gel electrophoresis (GGE) and nuclear magnetic resonance (NMR) spectroscopy are both widely accepted methods for measuring LDL and HDL particle size. However, whether or not GGE- or NMR-measured LDL or HDL particle size predicts coronary heart disease (CHD) risk to a similar extent is currently unknown. METHODS We used GGE and NMR to measure LDL and HDL particle size in a nested case-control study of 1025 incident cases of CHD and 1915 controls from the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk study. The study sample included apparently healthy men and women age 45-79 years followed for an average of 6 years. RESULTS Pearson correlation coefficients showed that the overall agreement between NMR and GGE was better for the measurement of HDL size (r = 0.78) than for LDL size (r = 0.47). The odds ratio for future CHD among participants in the bottom tertile of LDL size (smallest LDL particles) was 1.35 (95% CI, 1.12-1.63) for GGE and 1.74 (1.41-2.15) for NMR. For HDL size, these respective odds ratios were 1.41 (1.16-1.72) and 1.85 (1.47-2.32). After adjustment for potential confounders, the relationship between small LDL or HDL particles and CHD was no longer significant, irrespective of the method. CONCLUSIONS In this prospective population study, we found that the relationships between NMR-measured LDL and HDL sizes and CHD risk were slightly higher than those obtained with GGE.

[1]  H. Superko Advanced Lipoprotein Testing and Subfractionation Are Clinically Useful , 2009, Circulation.

[2]  Christina Lindahl,et al.  High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: significance for cardiovascular risk: the IDEAL and EPIC-Norfolk studies. , 2008, Journal of the American College of Cardiology.

[3]  G. Assmann,et al.  PROCAM Study: risk prediction for myocardial infarction using microfluidic high-density lipoprotein (HDL) subfractionation is independent of HDL cholesterol , 2008, Clinical chemistry and laboratory medicine.

[4]  J. Pais de Barros,et al.  High serum cholesteryl ester transfer rates and small high-density lipoproteins are associated with young age in patients with acute myocardial infarction. , 2007, Journal of the American College of Cardiology.

[5]  J. Després,et al.  Cholesterol levels in small LDL particles predict the risk of coronary heart disease in the EPIC-Norfolk prospective population study. , 2007, European heart journal.

[6]  James O. Mudd,et al.  Beyond low-density lipoprotein cholesterol: defining the role of low-density lipoprotein heterogeneity in coronary artery disease. , 2007, Journal of the American College of Cardiology.

[7]  Anand Rohatgi,et al.  HDL cholesterol: physiology, pathophysiology, and management. , 2007, Current problems in cardiology.

[8]  W. Cromwell,et al.  Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy. , 2006, Clinics in laboratory medicine.

[9]  C. Heward,et al.  Disparate LDL phenotypic classification among 4 different methods assessing LDL particle characteristics. , 2006, Clinical chemistry.

[10]  M. Taskinen,et al.  Decreased High-Density Lipoprotein (HDL) Particle Size, Pre&bgr;-, and Large HDL Subspecies Concentration in Finnish Low-HDL Families: Relationship With Intima-Media Thickness , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[11]  M. Rizzo,et al.  Low-density lipoprotein size and cardiovascular risk assessment. , 2006, QJM : monthly journal of the Association of Physicians.

[12]  Z. Bloomgarden Dyslipidemia and the metabolic syndrome. , 2004, Diabetes care.

[13]  M. Taskinen,et al.  Study of agreement between LDL size as measured by nuclear magnetic resonance and gradient gel electrophoresiss⃞s⃞ The online version of this article (available at http://www.jlr.org) contains an additional two tables. Published, JLR Papers in Press, March 1, 2004. DOI 10.1194/jlr.M300395-JLR200 , 2004, Journal of Lipid Research.

[14]  J. Després,et al.  Impact of postprandial variation in triglyceridemia on low-density lipoprotein particle size. , 2003, Metabolism: clinical and experimental.

[15]  P. Ridker,et al.  Low-Density Lipoprotein Particle Concentration and Size as Determined by Nuclear Magnetic Resonance Spectroscopy as Predictors of Cardiovascular Disease in Women , 2002, Circulation.

[16]  Mitsuyo Okazaki,et al.  A new on-line dual enzymatic method for simultaneous quantification of cholesterol and triglycerides in lipoproteins by HPLC. , 2002, Journal of lipid research.

[17]  D. Mikhailidis,et al.  Beyond LDL-C – The Importance of Raising HDL-C , 2002, Current medical research and opinion.

[18]  J. Després,et al.  Reduced HDL particle size as an additional feature of the atherogenic dyslipidemia of abdominal obesity. , 2001, Journal of lipid research.

[19]  G. Dagenais,et al.  Evaluation and management of atherogenic dyslipidemia: beyond low-density lipoprotein cholesterol. , 2001, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[20]  C. Couillard,et al.  A new method for HDL particle sizing by polyacrylamide gradient gel electrophoresis using whole plasma. , 2001, Journal of lipid research.

[21]  N. Day,et al.  EPIC-Norfolk: study design and characteristics of the cohort. European Prospective Investigation of Cancer. , 1999, British journal of cancer.

[22]  G. Dagenais,et al.  Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study. , 1997, Circulation.

[23]  R. Krauss,et al.  A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction. , 1996, JAMA.

[24]  J. Després,et al.  The Dense LDL Phenotype: Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men , 1996, Diabetes Care.

[25]  S. Bhakdi,et al.  On the pathogenesis of atherosclerosis: enzymatic transformation of human low density lipoprotein to an atherogenic moiety , 1995, The Journal of experimental medicine.

[26]  G. Dagenais,et al.  Prevalence of dyslipidemic phenotypes in ischemic heart disease (prospective results from the Québec Cardiovascular Study) , 1995, The American journal of cardiology.

[27]  K. C. Tan,et al.  Fasting and postprandial determinants for the occurrence of small dense LDL species in non-insulin-dependent diabetic patients with and without hypertriglyceridaemia: the involvement of insulin, insulin precursor species and insulin resistance. , 1995, Atherosclerosis.

[28]  T. Lyons,et al.  Glycation and oxidation: a role in the pathogenesis of atherosclerosis. , 1993, The American journal of cardiology.

[29]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.