Skip to main content
Postgraduate Medical Journal logoLink to Postgraduate Medical Journal
. 2005 Jun;81(956):358–366. doi: 10.1136/pgmj.2004.025601

Pathophysiology of dyslipidaemia in the metabolic syndrome

G Kolovou 1, K Anagnostopoulou 1, D Cokkinos 1
PMCID: PMC1743285  PMID: 15937200

Abstract

The insulin resistance/metabolic syndrome is characterised by the variable coexistence of hyperinsulinaemia, obesity, dyslipidaemia, and hypertension. The pathogenesis of the syndrome has multiple origins, but obesity and sedentary lifestyle coupled with diet and still largely unknown genetic factors clearly interact to produce the syndrome. Dyslipidaemia, the hallmark of the metabolic syndrome, includes increased flux of free fatty acids, raised triglycerides, apolipoprotein B, and small dense low density lipoprotein, and decreased high density lipoprotein cholesterol. The widely prevalent nature of the metabolic syndrome emphasises the importance of its diagnosis and treatment. This review analyses the clinical and dynamic features of this syndrome in the aspect of dyslipidaemia and its management.

Full Text

The Full Text of this article is available as a PDF (126.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alberti K. G., Zimmet P. Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998 Jul;15(7):539–553. doi: 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S. [DOI] [PubMed] [Google Scholar]
  2. Anderson Jeffrey L., Horne Benjamin D., Jones Heath U., Reyna Sandra P., Carlquist John F., Bair Tami L., Pearson Robert R., Lappé Donald L., Muhlestein Joseph B., Intermountain Heart Collaborative (IHC) Study Which features of the metabolic syndrome predict the prevalence and clinical outcomes of angiographic coronary artery disease? Cardiology. 2004 Feb 12;101(4):185–193. doi: 10.1159/000076695. [DOI] [PubMed] [Google Scholar]
  3. Arai T., Yamashita S., Hirano K., Sakai N., Kotani K., Fujioka S., Nozaki S., Keno Y., Yamane M., Shinohara E. Increased plasma cholesteryl ester transfer protein in obese subjects. A possible mechanism for the reduction of serum HDL cholesterol levels in obesity. Arterioscler Thromb. 1994 Jul;14(7):1129–1136. doi: 10.1161/01.atv.14.7.1129. [DOI] [PubMed] [Google Scholar]
  4. Ashavaid Tester F., Shalia Kavita K., Kondkar Altaf A., Todur Seema P., Nair Kappiareth G., Nair Sunita R. Gene polymorphism and coronary risk factors in Indian population. Clin Chem Lab Med. 2002 Oct;40(10):975–985. doi: 10.1515/CCLM.2002.171. [DOI] [PubMed] [Google Scholar]
  5. Balkau Beverley, Charles Marie-Aline, Drivsholm Thomas, Borch-Johnsen Knut, Wareham Nick, Yudkin John S., Morris Richard, Zavaroni Ivana, van Dam Rob, Feskins Edith. Frequency of the WHO metabolic syndrome in European cohorts, and an alternative definition of an insulin resistance syndrome. Diabetes Metab. 2002 Nov;28(5):364–376. [PubMed] [Google Scholar]
  6. Boden G. Fatty acids and insulin resistance. Diabetes Care. 1996 Apr;19(4):394–395. doi: 10.2337/diacare.19.4.394. [DOI] [PubMed] [Google Scholar]
  7. Brousseau Margaret E., Schaefer Ernst J., Wolfe Megan L., Bloedon LeAnne T., Digenio Andres G., Clark Ronald W., Mancuso James P., Rader Daniel J. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med. 2004 Apr 8;350(15):1505–1515. doi: 10.1056/NEJMoa031766. [DOI] [PubMed] [Google Scholar]
  8. Chait A., Brazg R. L., Tribble D. L., Krauss R. M. Susceptibility of small, dense, low-density lipoproteins to oxidative modification in subjects with the atherogenic lipoprotein phenotype, pattern B. Am J Med. 1993 Apr;94(4):350–356. doi: 10.1016/0002-9343(93)90144-e. [DOI] [PubMed] [Google Scholar]
  9. Chan Dick C., Barrett Hugh P. R., Watts Gerald F. Dyslipidemia in visceral obesity: mechanisms, implications, and therapy. Am J Cardiovasc Drugs. 2004;4(4):227–246. doi: 10.2165/00129784-200404040-00004. [DOI] [PubMed] [Google Scholar]
  10. Chan Dick C., Watts Gerald F., Barrett P. Hugh R., O'Neill Frans H., Redgrave Trevor G., Thompson Gilbert R. Relationships between cholesterol homoeostasis and triacylglycerol-rich lipoprotein remnant metabolism in the metabolic syndrome. Clin Sci (Lond) 2003 Apr;104(4):383–388. doi: 10.1042/cs1040383. [DOI] [PubMed] [Google Scholar]
  11. Chinetti G., Gbaguidi F. G., Griglio S., Mallat Z., Antonucci M., Poulain P., Chapman J., Fruchart J. C., Tedgui A., Najib-Fruchart J. CLA-1/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferator-activated receptors. Circulation. 2000 May 23;101(20):2411–2417. doi: 10.1161/01.cir.101.20.2411. [DOI] [PubMed] [Google Scholar]
  12. Clement Karine, Boutin Philippe, Froguel Philippe. Genetics of obesity. Am J Pharmacogenomics. 2002;2(3):177–187. doi: 10.2165/00129785-200202030-00003. [DOI] [PubMed] [Google Scholar]
  13. Collins Rory, Armitage Jane, Parish Sarah, Sleigh Peter, Peto Richard, Heart Protection Study Collaborative Group MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003 Jun 14;361(9374):2005–2016. doi: 10.1016/s0140-6736(03)13636-7. [DOI] [PubMed] [Google Scholar]
  14. Cooper A. D. Hepatic uptake of chylomicron remnants. J Lipid Res. 1997 Nov;38(11):2173–2192. [PubMed] [Google Scholar]
  15. Corella Dolores, Ordovas Jose M. The metabolic syndrome: a crossroad for genotype-phenotype associations in atherosclerosis. Curr Atheroscler Rep. 2004 May;6(3):186–196. doi: 10.1007/s11883-004-0031-8. [DOI] [PubMed] [Google Scholar]
  16. Couillard C., Bergeron N., Prud'homme D., Bergeron J., Tremblay A., Bouchard C., Mauriège P., Després J. P. Postprandial triglyceride response in visceral obesity in men. Diabetes. 1998 Jun;47(6):953–960. doi: 10.2337/diabetes.47.6.953. [DOI] [PubMed] [Google Scholar]
  17. Cummings M. H., Watts G. F., Umpleby A. M., Hennessy T. R., Kelly J. M., Jackson N. C., Sönksen P. H. Acute hyperinsulinemia decreases the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 in NIDDM. Diabetes. 1995 Sep;44(9):1059–1065. doi: 10.2337/diab.44.9.1059. [DOI] [PubMed] [Google Scholar]
  18. Downs J. R., Clearfield M., Weis S., Whitney E., Shapiro D. R., Beere P. A., Langendorfer A., Stein E. A., Kruyer W., Gotto A. M., Jr Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998 May 27;279(20):1615–1622. doi: 10.1001/jama.279.20.1615. [DOI] [PubMed] [Google Scholar]
  19. Drayna D., Jarnagin A. S., McLean J., Henzel W., Kohr W., Fielding C., Lawn R. Cloning and sequencing of human cholesteryl ester transfer protein cDNA. Nature. 1987 Jun 18;327(6123):632–634. doi: 10.1038/327632a0. [DOI] [PubMed] [Google Scholar]
  20. Festa A., D'Agostino R., Jr, Howard G., Mykkänen L., Tracy R. P., Haffner S. M. Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation. 2000 Jul 4;102(1):42–47. doi: 10.1161/01.cir.102.1.42. [DOI] [PubMed] [Google Scholar]
  21. Ford Earl S., Giles Wayne H., Dietz William H. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002 Jan 16;287(3):356–359. doi: 10.1001/jama.287.3.356. [DOI] [PubMed] [Google Scholar]
  22. Gervois P., Torra I. P., Fruchart J. C., Staels B. Regulation of lipid and lipoprotein metabolism by PPAR activators. Clin Chem Lab Med. 2000 Jan;38(1):3–11. doi: 10.1515/CCLM.2000.002. [DOI] [PubMed] [Google Scholar]
  23. Ginsberg H. N., Huang L. S. The insulin resistance syndrome: impact on lipoprotein metabolism and atherothrombosis. J Cardiovasc Risk. 2000 Oct;7(5):325–331. doi: 10.1177/204748730000700505. [DOI] [PubMed] [Google Scholar]
  24. Ginsberg H. N., Le N. A., Goldberg I. J., Gibson J. C., Rubinstein A., Wang-Iverson P., Norum R., Brown W. V. Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI. Evidence that apolipoprotein CIII inhibits catabolism of triglyceride-rich lipoproteins by lipoprotein lipase in vivo. J Clin Invest. 1986 Nov;78(5):1287–1295. doi: 10.1172/JCI112713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Goldberg R. B., Mellies M. J., Sacks F. M., Moyé L. A., Howard B. V., Howard W. J., Davis B. R., Cole T. G., Pfeffer M. A., Braunwald E. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. The Care Investigators. Circulation. 1998 Dec 8;98(23):2513–2519. doi: 10.1161/01.cir.98.23.2513. [DOI] [PubMed] [Google Scholar]
  26. Goldstein Barry J. Insulin resistance: from benign to type 2 diabetes mellitus. Rev Cardiovasc Med. 2003;4 (Suppl 6):S3–10. [PubMed] [Google Scholar]
  27. Goldstein J. L., Schrott H. G., Hazzard W. R., Bierman E. L., Motulsky A. G. Hyperlipidemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia. J Clin Invest. 1973 Jul;52(7):1544–1568. doi: 10.1172/JCI107332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Gorter Petra M., Olijhoek Jobien K., van der Graaf Yolanda, Algra Ale, Rabelink Ton J., Visseren Frank L. J., SMART Study Group Prevalence of the metabolic syndrome in patients with coronary heart disease, cerebrovascular disease, peripheral arterial disease or abdominal aortic aneurysm. Atherosclerosis. 2004 Apr;173(2):363–369. doi: 10.1016/j.atherosclerosis.2003.12.033. [DOI] [PubMed] [Google Scholar]
  29. Gudnason V., Kakko S., Nicaud V., Savolainen M. J., Kesäniemi Y. A., Tahvanainen E., Humphries S. Cholesteryl ester transfer protein gene effect on CETP activity and plasma high-density lipoprotein in European populations. The EARS Group. Eur J Clin Invest. 1999 Feb;29(2):116–128. doi: 10.1046/j.1365-2362.1999.00412.x. [DOI] [PubMed] [Google Scholar]
  30. Guyton J. R. Combination drug therapy for combined hyperlipidemia. Curr Cardiol Rep. 1999 Sep;1(3):244–250. doi: 10.1007/s11886-999-0030-z. [DOI] [PubMed] [Google Scholar]
  31. Haffner S. M., Alexander C. M., Cook T. J., Boccuzzi S. J., Musliner T. A., Pedersen T. R., Kjekshus J., Pyörälä K. Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels: subgroup analyses in the Scandinavian Simvastatin Survival Study. Arch Intern Med. 1999 Dec 13;159(22):2661–2667. doi: 10.1001/archinte.159.22.2661. [DOI] [PubMed] [Google Scholar]
  32. Haffner S. M., Lehto S., Rönnemaa T., Pyörälä K., Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998 Jul 23;339(4):229–234. doi: 10.1056/NEJM199807233390404. [DOI] [PubMed] [Google Scholar]
  33. Haluzík M., Parízková J., Haluzík M. M. Adiponectin and its role in the obesity-induced insulin resistance and related complications. Physiol Res. 2004;53(2):123–129. [PubMed] [Google Scholar]
  34. Hsia Judith, Bittner Vera, Tripputi Mark, Howard Barbara V. Metabolic syndrome and coronary angiographic disease progression: the Women's Angiographic Vitamin & Estrogen trial. Am Heart J. 2003 Sep;146(3):439–445. doi: 10.1016/S0002-8703(03)00227-8. [DOI] [PubMed] [Google Scholar]
  35. Isomaa B., Almgren P., Tuomi T., Forsén B., Lahti K., Nissén M., Taskinen M. R., Groop L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001 Apr;24(4):683–689. doi: 10.2337/diacare.24.4.683. [DOI] [PubMed] [Google Scholar]
  36. Jarvik G. P., Brunzell J. D., Austin M. A., Krauss R. M., Motulsky A. G., Wijsman E. Genetic predictors of FCHL in four large pedigrees. Influence of ApoB level major locus predicted genotype and LDL subclass phenotype. Arterioscler Thromb. 1994 Nov;14(11):1687–1694. doi: 10.1161/01.atv.14.11.1687. [DOI] [PubMed] [Google Scholar]
  37. Ji Quihe, Ikegami Hiroshi, Fujisawa Tomomi, Kawabata Yumiko, Ono Masaya, Nishino Masanori, Ohishi Mitsuru, Katsuya Tomohiro, Rakugi Hiromi, Ogihara Toshio. A common polymorphism of uncoupling protein 2 gene is associated with hypertension. J Hypertens. 2004 Jan;22(1):97–102. doi: 10.1097/00004872-200401000-00018. [DOI] [PubMed] [Google Scholar]
  38. Karpe Fredrik, Frayn Keith N. The nicotinic acid receptor--a new mechanism for an old drug. Lancet. 2004 Jun 5;363(9424):1892–1894. doi: 10.1016/S0140-6736(04)16359-9. [DOI] [PubMed] [Google Scholar]
  39. Keech Anthony, Colquhoun David, Best James, Kirby Adrienne, Simes R. John, Hunt David, Hague Wendy, Beller Elaine, Arulchelvam Manjula, Baker Jennifer. Secondary prevention of cardiovascular events with long-term pravastatin in patients with diabetes or impaired fasting glucose: results from the LIPID trial. Diabetes Care. 2003 Oct;26(10):2713–2721. doi: 10.2337/diacare.26.10.2713. [DOI] [PubMed] [Google Scholar]
  40. Knopp R. H., Walden C. E., Retzlaff B. M., McCann B. S., Dowdy A. A., Albers J. J., Gey G. O., Cooper M. N. Long-term cholesterol-lowering effects of 4 fat-restricted diets in hypercholesterolemic and combined hyperlipidemic men. The Dietary Alternatives Study. JAMA. 1997 Nov 12;278(18):1509–1515. [PubMed] [Google Scholar]
  41. Kolovou G. D., Anagnostopoulou K. K., Pilatis N. D., Iraklianou S., Hoursalas I. S., Liberi S., Pavlidis A. N., Dritsas A., Mikhailidis D. P., Cokkinos D. V. Heterozygote men with familial hypercholesterolaemia may have an abnormal triglyceride response post-prandially. Evidence for another predictor of vascular risk in familial hypercholesterolaemia. Int J Clin Pract. 2005 Mar;59(3):311–317. doi: 10.1111/j.1742-1241.2004.00223.x. [DOI] [PubMed] [Google Scholar]
  42. Kolovou Genovefa D., Cokkinos Dennis V. Low serum levels of high-density lipoprotein cholesterol and hypolipidaemic treatment. Curr Med Res Opin. 2002;18(5):265–268. doi: 10.1185/030079902125000534. [DOI] [PubMed] [Google Scholar]
  43. Kolovou Genovefa D., Daskalova Deliana C., Petropoulos Ilias I., Anagnostopoulou Katherine K., Bilianou Helen I., Pilatis Nektarios D., Pavlidis Antonis N., Cokkinos Dennis V. Effect of baseline levels on response of high-density lipoprotein cholesterol to hypolipidemic treatment. Am J Cardiol. 2003 Dec 1;92(11):1339–1342. doi: 10.1016/j.amjcard.2003.08.022. [DOI] [PubMed] [Google Scholar]
  44. Kolovou Genovefa D., Daskalova Deliana Ch, Iraklianou Stella A., Adamopoulou Evdokia N., Pilatis Nektarios D., Hatzigeorgiou Georgios C., Cokkinos Dennis V. Postprandial lipemia in hypertension. J Am Coll Nutr. 2003 Feb;22(1):80–87. doi: 10.1080/07315724.2003.10719279. [DOI] [PubMed] [Google Scholar]
  45. Kwiterovich P. O., Jr, Coresh J., Bachorik P. S. Prevalence of hyperapobetalipoproteinemia and other lipoprotein phenotypes in men (aged < or = 50 years) and women (< or = 60 years) with coronary artery disease. Am J Cardiol. 1993 Mar 15;71(8):631–639. doi: 10.1016/0002-9149(93)91002-y. [DOI] [PubMed] [Google Scholar]
  46. Kwiterovich P. O., Jr, Coresh J., Smith H. H., Bachorik P. S., Derby C. A., Pearson T. A. Comparison of the plasma levels of apolipoproteins B and A-1, and other risk factors in men and women with premature coronary artery disease. Am J Cardiol. 1992 Apr 15;69(12):1015–1021. doi: 10.1016/0002-9149(92)90856-t. [DOI] [PubMed] [Google Scholar]
  47. Kwiterovich Peter O., Jr Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity. Am J Cardiol. 2002 Oct 17;90(8A):30i–47i. doi: 10.1016/s0002-9149(02)02749-2. [DOI] [PubMed] [Google Scholar]
  48. Lakka H-M, Lakka T. A., Tuomilehto J., Salonen J. T. Abdominal obesity is associated with increased risk of acute coronary events in men. Eur Heart J. 2002 May;23(9):706–713. doi: 10.1053/euhj.2001.2889. [DOI] [PubMed] [Google Scholar]
  49. Lamarche B., Tchernof A., Mauriège P., Cantin B., Dagenais G. R., Lupien P. J., Després J. P. Fasting insulin and apolipoprotein B levels and low-density lipoprotein particle size as risk factors for ischemic heart disease. JAMA. 1998 Jun 24;279(24):1955–1961. doi: 10.1001/jama.279.24.1955. [DOI] [PubMed] [Google Scholar]
  50. Lee Kenny W. J., Ayyobi Amir F., Frohlich Jiri J., Hill John S. APOA5 gene polymorphism modulates levels of triglyceride, HDL cholesterol and FERHDL but is not a risk factor for coronary artery disease. Atherosclerosis. 2004 Sep;176(1):165–172. doi: 10.1016/j.atherosclerosis.2004.04.024. [DOI] [PubMed] [Google Scholar]
  51. Lewis G. F., Uffelman K. D., Szeto L. W., Steiner G. Effects of acute hyperinsulinemia on VLDL triglyceride and VLDL apoB production in normal weight and obese individuals. Diabetes. 1993 Jun;42(6):833–842. doi: 10.2337/diab.42.6.833. [DOI] [PubMed] [Google Scholar]
  52. Lewis G. F., Uffelman K. D., Szeto L. W., Weller B., Steiner G. Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans. J Clin Invest. 1995 Jan;95(1):158–166. doi: 10.1172/JCI117633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Malczewska-Malec Małgorzata, Wybranska Iwona, Leszczynska-Golabek Iwona, Partyka Lukasz, Hartwich Jadwiga, Jabrocka Agata, Kiec-Wilk Beata, Kwasniak Małgorzata, Motyka Marcin, Dembinska-Kiec Aldona. Analysis of candidate genes in Polish families with obesity. Clin Chem Lab Med. 2004 May;42(5):487–493. doi: 10.1515/CCLM.2004.083. [DOI] [PubMed] [Google Scholar]
  54. Malmström R., Packard C. J., Watson T. D., Rannikko S., Caslake M., Bedford D., Stewart P., Yki-Järvinen H., Shepherd J., Taskinen M. R. Metabolic basis of hypotriglyceridemic effects of insulin in normal men. Arterioscler Thromb Vasc Biol. 1997 Jul;17(7):1454–1464. doi: 10.1161/01.atv.17.7.1454. [DOI] [PubMed] [Google Scholar]
  55. Martin G., Duez H., Blanquart C., Berezowski V., Poulain P., Fruchart J. C., Najib-Fruchart J., Glineur C., Staels B. Statin-induced inhibition of the Rho-signaling pathway activates PPARalpha and induces HDL apoA-I. J Clin Invest. 2001 Jun;107(11):1423–1432. doi: 10.1172/JCI10852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Matsuzawa Yuji, Funahashi Tohru, Kihara Shinji, Shimomura Iichiro. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol. 2003 Oct 9;24(1):29–33. doi: 10.1161/01.ATV.0000099786.99623.EF. [DOI] [PubMed] [Google Scholar]
  57. Mazzone T., Foster D., Chait A. In vivo stimulation of low-density lipoprotein degradation by insulin. Diabetes. 1984 Apr;33(4):333–338. doi: 10.2337/diab.33.4.333. [DOI] [PubMed] [Google Scholar]
  58. McFarlane S. I., Banerji M., Sowers J. R. Insulin resistance and cardiovascular disease. J Clin Endocrinol Metab. 2001 Feb;86(2):713–718. doi: 10.1210/jcem.86.2.7202. [DOI] [PubMed] [Google Scholar]
  59. Meigs James B., Wilson Peter W. F., Nathan David M., D'Agostino Ralph B., Sr, Williams Ken, Haffner Steven M. Prevalence and characteristics of the metabolic syndrome in the San Antonio Heart and Framingham Offspring Studies. Diabetes. 2003 Aug;52(8):2160–2167. doi: 10.2337/diabetes.52.8.2160. [DOI] [PubMed] [Google Scholar]
  60. Merkel Martin, Eckel Robert H., Goldberg Ira J. Lipoprotein lipase: genetics, lipid uptake, and regulation. J Lipid Res. 2002 Dec;43(12):1997–2006. doi: 10.1194/jlr.r200015-jlr200. [DOI] [PubMed] [Google Scholar]
  61. Messerli Adrian W., Seshadri Niranjan, Pearce Gregory L., Sachar Ravish, Hoogwerf Byron J., Sprecher Dennis L. Relation of albumin/creatinine ratio to C-reactive protein and to the metabolic syndrome. Am J Cardiol. 2003 Sep 1;92(5):610–612. doi: 10.1016/s0002-9149(03)00736-7. [DOI] [PubMed] [Google Scholar]
  62. Morabia Alfredo, Ross Barbara M., Costanza Michael C., Cayanis Eftihia, Flaherty Maria Sol, Alvin Gabriela B., Das Kamna, James Richard, Yang An-Suei, Evagrafov Oleg. Population-based study of SR-BI genetic variation and lipid profile. Atherosclerosis. 2004 Jul;175(1):159–168. doi: 10.1016/j.atherosclerosis.2004.03.014. [DOI] [PubMed] [Google Scholar]
  63. Morton R. E. Cholesteryl ester transfer protein and its plasma regulator: lipid transfer inhibitor protein. Curr Opin Lipidol. 1999 Aug;10(4):321–327. doi: 10.1097/00041433-199908000-00006. [DOI] [PubMed] [Google Scholar]
  64. Ninomiya John K., L'Italien Gilbert, Criqui Michael H., Whyte Joanna L., Gamst Anthony, Chen Roland S. Association of the metabolic syndrome with history of myocardial infarction and stroke in the Third National Health and Nutrition Examination Survey. Circulation. 2003 Dec 15;109(1):42–46. doi: 10.1161/01.CIR.0000108926.04022.0C. [DOI] [PubMed] [Google Scholar]
  65. Packard C. J., Demant T., Stewart J. P., Bedford D., Caslake M. J., Schwertfeger G., Bedynek A., Shepherd J., Seidel D. Apolipoprotein B metabolism and the distribution of VLDL and LDL subfractions. J Lipid Res. 2000 Feb;41(2):305–318. [PubMed] [Google Scholar]
  66. Packard C. J. Triacylglycerol-rich lipoproteins and the generation of small, dense low-density lipoprotein. Biochem Soc Trans. 2003 Oct;31(Pt 5):1066–1069. doi: 10.1042/bst0311066. [DOI] [PubMed] [Google Scholar]
  67. Patsch J. R., Miesenböck G., Hopferwieser T., Mühlberger V., Knapp E., Dunn J. K., Gotto A. M., Jr, Patsch W. Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state. Arterioscler Thromb. 1992 Nov;12(11):1336–1345. doi: 10.1161/01.atv.12.11.1336. [DOI] [PubMed] [Google Scholar]
  68. Pauciullo P., Borgnino C., Paoletti R., Mariani M., Mancini M. Efficacy and safety of a combination of fluvastatin and bezafibrate in patients with mixed hyperlipidaemia (FACT study). Atherosclerosis. 2000 Jun;150(2):429–436. doi: 10.1016/s0021-9150(00)00379-8. [DOI] [PubMed] [Google Scholar]
  69. Pinhas-Hamiel O., Dolan L. M., Daniels S. R., Standiford D., Khoury P. R., Zeitler P. Increased incidence of non-insulin-dependent diabetes mellitus among adolescents. J Pediatr. 1996 May;128(5 Pt 1):608–615. doi: 10.1016/s0022-3476(96)80124-7. [DOI] [PubMed] [Google Scholar]
  70. Prinsen Berthil H. C. M. T., Romijn Johannes A., Bisschop Peter H., de Barse Martina M. J., Barrett P. Hugh R., Ackermans Mariëtte, Berger Ruud, Rabelink Ton J., de Sain-van der Velden Monique G. M. Endogenous cholesterol synthesis is associated with VLDL-2 apoB-100 production in healthy humans. J Lipid Res. 2003 Apr 16;44(7):1341–1348. doi: 10.1194/jlr.M300023-JLR200. [DOI] [PubMed] [Google Scholar]
  71. Rainwater D. L., Mitchell B. D., Mahaney M. C., Haffner S. M. Genetic relationship between measures of HDL phenotypes and insulin concentrations. Arterioscler Thromb Vasc Biol. 1997 Dec;17(12):3414–3419. doi: 10.1161/01.atv.17.12.3414. [DOI] [PubMed] [Google Scholar]
  72. Ravussin E., Valencia M. E., Esparza J., Bennett P. H., Schulz L. O. Effects of a traditional lifestyle on obesity in Pima Indians. Diabetes Care. 1994 Sep;17(9):1067–1074. doi: 10.2337/diacare.17.9.1067. [DOI] [PubMed] [Google Scholar]
  73. Reaven G. M. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988 Dec;37(12):1595–1607. doi: 10.2337/diab.37.12.1595. [DOI] [PubMed] [Google Scholar]
  74. Rebuffé-Scrive M., Lönnroth P., Mårin P., Wesslau C., Björntorp P., Smith U. Regional adipose tissue metabolism in men and postmenopausal women. Int J Obes. 1987;11(4):347–355. [PubMed] [Google Scholar]
  75. Reilly Muredach P., Rader Daniel J. The metabolic syndrome: more than the sum of its parts? Circulation. 2003 Sep 30;108(13):1546–1551. doi: 10.1161/01.CIR.0000088846.10655.E0. [DOI] [PubMed] [Google Scholar]
  76. Rubic Tina, Trottmann Matthias, Lorenz Reinhard L. Stimulation of CD36 and the key effector of reverse cholesterol transport ATP-binding cassette A1 in monocytoid cells by niacin. Biochem Pharmacol. 2004 Feb 1;67(3):411–419. doi: 10.1016/j.bcp.2003.09.014. [DOI] [PubMed] [Google Scholar]
  77. Rust S., Rosier M., Funke H., Real J., Amoura Z., Piette J. C., Deleuze J. F., Brewer H. B., Duverger N., Denèfle P. Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1. Nat Genet. 1999 Aug;22(4):352–355. doi: 10.1038/11921. [DOI] [PubMed] [Google Scholar]
  78. Sacco R. L., Benson R. T., Kargman D. E., Boden-Albala B., Tuck C., Lin I. F., Cheng J. F., Paik M. C., Shea S., Berglund L. High-density lipoprotein cholesterol and ischemic stroke in the elderly: the Northern Manhattan Stroke Study. JAMA. 2001 Jun 6;285(21):2729–2735. doi: 10.1001/jama.285.21.2729. [DOI] [PubMed] [Google Scholar]
  79. Sattar Naveed, Gaw Allan, Scherbakova Olga, Ford Ian, O'Reilly Denis St J., Haffner Steven M., Isles Chris, Macfarlane Peter W., Packard Chris J., Cobbe Stuart M. Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation. 2003 Jul 14;108(4):414–419. doi: 10.1161/01.CIR.0000080897.52664.94. [DOI] [PubMed] [Google Scholar]
  80. Semenkovich Clay F. Fatty acid metabolism and vascular disease. Trends Cardiovasc Med. 2004 Feb;14(2):72–76. doi: 10.1016/j.tcm.2003.12.004. [DOI] [PubMed] [Google Scholar]
  81. Sethi Amar Akhtar, Nordestgaard Børge Grønne, Tybjaerg-Hansen Anne. Angiotensinogen gene polymorphism, plasma angiotensinogen, and risk of hypertension and ischemic heart disease: a meta-analysis. Arterioscler Thromb Vasc Biol. 2003 Jun 12;23(7):1269–1275. doi: 10.1161/01.ATV.0000079007.40884.5C. [DOI] [PubMed] [Google Scholar]
  82. Shek A., Ferrill M. J. Statin-fibrate combination therapy. Ann Pharmacother. 2001 Jul-Aug;35(7-8):908–917. doi: 10.1345/aph.10315. [DOI] [PubMed] [Google Scholar]
  83. Simonen P., Gylling H., Howard A. N., Miettinen T. A. Introducing a new component of the metabolic syndrome: low cholesterol absorption. Am J Clin Nutr. 2000 Jul;72(1):82–88. doi: 10.1093/ajcn/72.1.82. [DOI] [PubMed] [Google Scholar]
  84. Sniderman A. D., Castro Cabezas M., Ribalta J., Carmena R., de Bruin T. W. A., de Graaf J., Erkelens D. W., Humphries S. E., Masana L., Real J. T. A proposal to redefine familial combined hyperlipidaemia -- third workshop on FCHL held in Barcelona from 3 to 5 May 2001, during the scientific sessions of the European Society for Clinical Investigation. Eur J Clin Invest. 2002 Feb;32(2):71–73. doi: 10.1046/j.1365-2362.2002.00941.x. [DOI] [PubMed] [Google Scholar]
  85. Staels B., Auwerx J. Regulation of apo A-I gene expression by fibrates. Atherosclerosis. 1998 Apr;137 (Suppl):S19–S23. doi: 10.1016/s0021-9150(97)00313-4. [DOI] [PubMed] [Google Scholar]
  86. Staels B., Dallongeville J., Auwerx J., Schoonjans K., Leitersdorf E., Fruchart J. C. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation. 1998 Nov 10;98(19):2088–2093. doi: 10.1161/01.cir.98.19.2088. [DOI] [PubMed] [Google Scholar]
  87. Streja Dan. Combination therapy for the treatment of dyslipidemia. Curr Opin Investig Drugs. 2004 Mar;5(3):306–312. [PubMed] [Google Scholar]
  88. Sudhop Thomas, Lütjohann Dieter, Kodal Annette, Igel Michael, Tribble Diane L., Shah Sukrut, Perevozskaya Inna, von Bergmann Klaus. Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation. 2002 Oct 8;106(15):1943–1948. doi: 10.1161/01.cir.0000034044.95911.dc. [DOI] [PubMed] [Google Scholar]
  89. Taira K., Hikita M., Kobayashi J., Bujo H., Takahashi K., Murano S., Morisaki N., Saito Y. Delayed post-prandial lipid metabolism in subjects with intra-abdominal visceral fat accumulation. Eur J Clin Invest. 1999 Apr;29(4):301–308. doi: 10.1046/j.1365-2362.1999.00454.x. [DOI] [PubMed] [Google Scholar]
  90. Tatò F., Vega G. L., Grundy S. M. Effects of crystalline nicotinic acid-induced hepatic dysfunction on serum low-density lipoprotein cholesterol and lecithin cholesteryl acyl transferase. Am J Cardiol. 1998 Mar 15;81(6):805–807. doi: 10.1016/s0002-9149(97)01016-3. [DOI] [PubMed] [Google Scholar]
  91. Thompson G. R., Naoumova R. P., Watts G. F. Role of cholesterol in regulating apolipoprotein B secretion by the liver. J Lipid Res. 1996 Mar;37(3):439–447. [PubMed] [Google Scholar]
  92. Trayhurn P., Beattie J. H. Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc. 2001 Aug;60(3):329–339. doi: 10.1079/pns200194. [DOI] [PubMed] [Google Scholar]
  93. Vega Gloria Lena, Ma Patrick T. S., Cater Nilo B., Filipchuk Neil, Meguro Shinichi, Garcia-Garcia Ana Barbara, Grundy Scott M. Effects of adding fenofibrate (200 mg/day) to simvastatin (10 mg/day) in patients with combined hyperlipidemia and metabolic syndrome. Am J Cardiol. 2003 Apr 15;91(8):956–960. doi: 10.1016/s0002-9149(03)00111-5. [DOI] [PubMed] [Google Scholar]
  94. Vinicor F. Is diabetes a public-health disorder? Diabetes Care. 1994 Jun;17 (Suppl 1):22–27. [PubMed] [Google Scholar]
  95. Väisänen S., Baumstark M. W., Penttilä I., Bouchard C., Halonen P., Rankinen T., Berg A., Rauramaa R. Small, dense LDL particle concentration correlates with plasminogen activator inhibitor type-1 (PAI-1) activity. Thromb Haemost. 1997 Dec;78(6):1495–1499. [PubMed] [Google Scholar]
  96. Wang Ji-Guang, Liu Lifang, Zagato Laura, Xie Jinxiang, Fagard Robert, Jin Kugen, Wang Jinxiang, Li Yan, Bianchi Giuseppe, Staessen Jan A. Blood pressure in relation to three candidate genes in a Chinese population. J Hypertens. 2004 May;22(5):937–944. doi: 10.1097/00004872-200405000-00015. [DOI] [PubMed] [Google Scholar]
  97. Wang Yutong, Kurdi-Haidar Buran, Oram John F. LXR-mediated activation of macrophage stearoyl-CoA desaturase generates unsaturated fatty acids that destabilize ABCA1. J Lipid Res. 2004 Feb 16;45(5):972–980. doi: 10.1194/jlr.M400011-JLR200. [DOI] [PubMed] [Google Scholar]
  98. Wierzbicki A. S., Mikhailidis D. P., Wray R., Schacter M., Cramb R., Simpson W. G., Byrne C. B. Statin-fibrate combination: therapy for hyperlipidemia: a review. Curr Med Res Opin. 2003;19(3):155–168. doi: 10.1185/030079903125001668. [DOI] [PubMed] [Google Scholar]
  99. Wilson Peter W. F., Grundy Scott M. The metabolic syndrome: practical guide to origins and treatment: Part I. Circulation. 2003 Sep 23;108(12):1422–1424. doi: 10.1161/01.CIR.0000089505.34741.E5. [DOI] [PubMed] [Google Scholar]
  100. de Grooth Greetje J., Kuivenhoven Jan Albert, Stalenhoef Anton F. H., de Graaf Jacqueline, Zwinderman Aeilko H., Posma Jan L., van Tol Arie, Kastelein John J. P. Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study. Circulation. 2002 May 7;105(18):2159–2165. doi: 10.1161/01.cir.0000015857.31889.7b. [DOI] [PubMed] [Google Scholar]
  101. van Dijk Ko Willems, Rensen Patrick C. N., Voshol Peter J., Havekes Louis M. The role and mode of action of apolipoproteins CIII and AV: synergistic actors in triglyceride metabolism? Curr Opin Lipidol. 2004 Jun;15(3):239–246. doi: 10.1097/00041433-200406000-00002. [DOI] [PubMed] [Google Scholar]

Articles from Postgraduate Medical Journal are provided here courtesy of BMJ Publishing Group

RESOURCES