SRX Pharmacology

SRX Pharmacology / 2010 / Article

Research Article | Open Access

Volume 2010 |Article ID 485146 | 8 pages |

Comparison of Postprandial Responses to a High-Fat Meal in Hypertriglyceridemic Men and Women before and after Treatment with Fenofibrate in the Genetics and Lipid Lowering Drugs and Diet Network (GOLDN) Study

Received26 Oct 2009
Accepted24 Nov 2009
Published18 Feb 2010


Context. The fenofibrate effect on the subclass size distribution of lipoproteins before and after a high-fat challenge is not well studied. Objective. To characterize the baseline and post-prandial response (PPL) to a high-fat challenge following fenofibrate therapy, on changes in LDL, HDL, and VLDL particle subclasses, number, and size in 271 hypertriglyceridemic participants. Methods. Participants from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study who conducted PPL studies both before and after three weeks of fenofibrate (160 mg/d) treatment were analyzed. Particle size distributions were determined using nuclear magnetic resonance imaging, and lipid determinations were measured at fasting (0 hr), 3.5 hours, and 6 hours after ingestion of a standardized high-fat meal. Analyses were stratified by gender. Changes in particle subclass distributions were assessed using repeated measures analysis of variance adjusted for pedigree. Results. Before PPL, fenofibrate in men (adjusted for age, field center, smoking status, diabetes, and weight circumference) lowered fasting and postprandial VLDL primarily due to reductions in postprandial levels of large and medium VLDL particles (9 SE +/0.7 to 4 +/0.4 and 78 =/4 to 36 =/3 nmol/L both P<.0001, resp.). Fenofibrate also reduced fasting and postprandial total LDL particles, primarily a result of reduced small LDL particles (1497 =/37 to 1088 =/36 nmol/L, P<.0001). Directional changes were similar in men and women but the magnitude of change was different for some parameters. Conclusion. Fenofibrate treatment resulted in a lower triglyceride excursion following a high-fat meal. This investigation provides new knowledge of the magnitude and time course of fenofibrate induced attenuation of Lipoprotein subclass size distribution following a postprandial lipid challenge.


  1. O. F. De Lalla and J. W. Grofman, “Ultracentrifugal analysis of serum lipoproteins,” Methods of Biochemical Analysis, vol. 1, pp. 459–478, 1954. View at: Google Scholar
  2. P. J. Blanche, E. L. Gong, T. M. Forte, and A. V. Nichols, “Characterization of human high-density lipoproteins by gradient gel electrophoresis,” Biochimica et Biophysica Acta, vol. 665, no. 3, pp. 408–419, 1981. View at: Google Scholar
  3. S. Mora, M. Szklo, J. D. Otvos et al., “LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA),” Atherosclerosis, vol. 192, no. 1, pp. 211–217, 2007. View at: Publisher Site | Google Scholar
  4. M. A. Austin, M.-C. King, K. M. Vranizan, and R. M. Krauss, “Atherogenic lipoprotein phenotype: a proposed genetic marker for coronary heart disease risk,” Circulation, vol. 82, no. 2, pp. 495–506, 1990. View at: Google Scholar
  5. M. Rizzo and K. Berneis, “Lipid triad or atherogenic lipoprotein phenotype: a role in cardiovascular prevention?” Journal of Atherosclerosis and Thrombosis, vol. 12, no. 5, pp. 237–239, 2005. View at: Google Scholar
  6. C. Couillard, N. Bergeron, D. Prud'homme et al., “Gender difference in postprandial lipemia: importance of visceral adipose tissue accumulation,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 19, no. 10, pp. 2448–2455, 1999. View at: Google Scholar
  7. J. Johansson, L. A. Carlson, C. Landou, and A. Hamsten, “High density lipoproteins and coronary atherosclerosis. A strong inverse relation with the largest particles is confined to normotriglyceridemic patients,” Arteriosclerosis and Thrombosis, vol. 11, no. 1, pp. 174–182, 1991. View at: Google Scholar
  8. H. M. Wilson, J. C. Patel, D. Russell, and E. R. Skinner, “Alterations in the concentration of an apolipoprotein E-containing subfraction of plasma high density lipoprotein in coronary heart disease,” Clinica Chimica Acta, vol. 220, no. 2, pp. 175–187, 1993. View at: Publisher Site | Google Scholar
  9. B. G. Nordestgaard, M. Benn, P. Schnohr, and A. Tybjærg-Hansen, “Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women,” Journal of the American Medical Association, vol. 298, no. 3, pp. 299–308, 2007. View at: Publisher Site | Google Scholar
  10. R. S. Rosenson, D. A. Wolff, A. L. Huskin, I. B. Helenowski, and A. W. Rademaker, “Fenofibrate therapy ameliorates fasting and postprandial lipoproteinemia, oxidative stress, and the inflammatory response in subjects with hypertriglyceridemia and the metabolic syndrome,” Diabetes Care, vol. 30, no. 8, pp. 1945–1951, 2007. View at: Publisher Site | Google Scholar
  11. K. Ikewaki, J. Tohyama, Y. Nakata, T. Wakikawa, T. Kido, and S. Mochizuki, “Fenofibrate effectively reduces remnants, and small dense LDL, and increases HDL particle number in hypertriglyceridemic men—a nuclear magnetic resonance study,” Journal of Atherosclerosis and Thrombosis, vol. 11, no. 5, pp. 278–285, 2004. View at: Google Scholar
  12. G. de la Serna and C. Cadarso, “Fenofibrate decreases plasma fibrinogen, improves lipid profile, and reduces uricemia,” Clinical Pharmacology and Therapeutics, vol. 66, no. 2, pp. 166–172, 1999. View at: Google Scholar
  13. I. Lemieux, L. Lapeierrere, V. Dzavik, G. Tremblay, J. Bourgeois, and J.-P. Depres, “A 16-week fenofibrate treatment increases LDL particle size in type IIA dyslipidemic patients,” Atherosclerosis, vol. 162, no. 2, pp. 363–371, 2002. View at: Publisher Site | Google Scholar
  14. J. R. Patsch, G. Miesenbock, T. Hopferwieser et al., “Relation of triglyceride metabolism and coronary artery disease: studies in the postprandial state,” Arteriosclerosis and Thrombosis, vol. 12, no. 11, pp. 1336–1345, 1992. View at: Google Scholar
  15. D. Corella, D. K. Arnett, M. Y. Tsai et al., “The -256T>C polymorphism in the apolipoprotein A-II gene promoter is associated with body mass index and food intake in the genetics of lipid lowering drugs and diet network study,” Clinical Chemistry, vol. 53, no. 6, pp. 1144–1152, 2007. View at: Publisher Site | Google Scholar
  16. M. Cushman, E. S. Cornell, P. R. Howard, E. G. Bovill, and R. P. Tracy, “Laboratory methods and quality assurance in the Cardiovascular Health Study,” Clinical Chemistry, vol. 41, no. 2, pp. 264–270, 1995. View at: Google Scholar
  17. J. D. Otvos, “Measurement of lipoprotein subclass profiles by nuclear magnetic resonance spectroscopy,” Clinical Laboratory, vol. 48, no. 3-4, pp. 171–180, 2002. View at: Google Scholar
  18. S. Mora, J. D. Otvos, N. Rifai, R. S. Rosenson, J. E. Buring, and P. M. Ridker, “Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women,” Circulation, vol. 119, no. 7, pp. 931–939, 2009. View at: Publisher Site | Google Scholar
  19. F. Forcheron, A. Cachefo, S. Thevenon, C. Pinteur, and M. Beylot, “Mechanisms of the triglyceride- and cholesterol-lowering effect of fenofibrate in hyperlipidemic type 2 diabetic patients,” Diabetes, vol. 51, no. 12, pp. 3486–3491, 2002. View at: Google Scholar
  20. J. C. Fruchart, B. Staels, and P. Duriez, “The role of fibric acids in atherosclerosis,” Current Atherosclerosis Reports, vol. 3, no. 1, pp. 83–92, 2001. View at: Google Scholar
  21. H. M. Wilson, J. C. Patel, and E. R. Skinner, “The distribution of high-density lipoprotein subfractions in coronary survivors,” Biochemical Society Transactions, vol. 18, no. 6, pp. 1175–1176, 1990. View at: Google Scholar
  22. B. F. Asztalos, D. Collins, L. A. Cupples et al., “Value of high-density lipoprotein (HDL) subpopulations in predicting recurrent cardiovascular events in the veterans affairs HDL intervention trial,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 10, pp. 2185–2191, 2005. View at: Publisher Site | Google Scholar
  23. J. D. Otvos, D. Collins, D. S. Freedman et al., “Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the veterans affairs high-density lipoprotein intervention trial,” Circulation, vol. 113, no. 12, pp. 1556–1563, 2006. View at: Publisher Site | Google Scholar
  24. G. Ruotolo, C.-G. Ericsson, C. Tettamanti et al., “Treatment effects on serum lipoprotein lipids, apolipoproteins and low density lipoprotein particle size and relationships of lipoprotein variables to progression of coronary artery disease in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT),” Journal of the American College of Cardiology, vol. 32, no. 6, pp. 1648–1656, 1998. View at: Publisher Site | Google Scholar
  25. S. Mora, N. Rifai, J. E. Buring, and P. M. Ridker, “Fasting compared with nonfasting lipids and apolipoproteins for predicting incident cardiovascular events,” Circulation, vol. 118, no. 10, pp. 993–1001, 2008. View at: Publisher Site | Google Scholar

Copyright © 2010 Stephen P. Glasser et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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