Fenofibrate and metabolic syndrome

Endocrine, Metabolic and Immune Disorders - Drug Targets

Volumn 10, Issue 2, 2010, Pages 138-148

  Kraja, Aldi T ^a   Province, Michael A ^a   Straka, Robert J ^b   Ordovas, Jose M ^c   Borecki, Ingrid B ^a   Arnett, Donna K ^d  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF MINNESOTA   (United States)

^c TUFTS UNIVERSITY   (United States)

^d UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

Clinical trials; Fenofibrate; Lipids; Metabolic syndrome; Multivariate analysis; Random coefficients model; Single nucleotide polymorphism

Indexed keywords

APOLIPOPROTEIN; ATORVASTATIN; BEZAFIBRATE; CHOLESTEROL; CLOFIBRATE; FENOFIBRATE; FIBRIC ACID DERIVATIVE; FLUINDOSTATIN; GEMFIBROZIL; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; MEVINOLIN; NITRIC OXIDE SYNTHASE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PRAVASTATIN; ROSUVASTATIN; SIMVASTATIN; TRIACYLGLYCEROL; TRILIPIX; UNCLASSIFIED DRUG;

ARTICLE; CARDIOVASCULAR RISK; CHOLESTEROL BLOOD LEVEL; CLINICAL TRIAL; DELAYED RELEASE FORMULATION; DRUG BIOAVAILABILITY; DRUG UPTAKE; DYSLIPIDEMIA; GENE EXPRESSION; GENETIC ASSOCIATION; GENETIC VARIABILITY; HEART INFARCTION; HUMAN; LIVER INJURY; METABOLIC SYNDROME X; MONOTHERAPY; MUSCLE WEAKNESS; MYALGIA; MYOPATHY; MYOSITIS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; RHABDOMYOLYSIS; STROKE; TREATMENT OUTCOME; TRIACYLGLYCEROL BLOOD LEVEL;

EID: 77954051832     PISSN: 18715303     EISSN: None     Source Type: Journal    
DOI: 10.2174/187153010791213047     Document Type: Article

References (109)

1. Scott, R.; Best, J.; Forder, P.; Taskinen, M.R.; Simes, J.; Barter, P.; Keech, A. and FIELD Study Investigators. (2005) Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: baseline characteristics and short-term effects of fenofibrate. Cardiovasc. Diabetol., 4, 13.
2. The ACCORD Study Group. (2010) Effects of combination lipid therapy in type 2 diabetes mellitus. N. Engl. J. Med., [Epub ahead of print ].
3. Grundy, S.M.; Cleeman, J.I.; Daniels, S.R.; Donato, K.A.; Eckel, R.H.; Franklin, B.A.; Gordon, D.J.; Krauss, R.M.; Savage, P.J.; Smith, S.C.Jr.; Spertus, J.A.; Costa, F.; American Heart Association; National Heart, Lung, and Blood Institutex. (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation, 112, 2735-2752.
4. Monda, K.L.; North, K.E.; Hunt, S.C.; Rao, D.C.; Province, M.A.; Kraja, A.T. (2010) The genetics of obesity and metabolic syndrome. Endocr. Metab. Immune. Disord. Drug Targets, 10, 86- 108.
5. Kraja, A.T.; Province, M.A.; Huang, P.; Jarvis, J.P.; Rice, T.; Cheverud, J.M. and Rao, D.C. (2008) Trends in metabolic syndrome and gene networks in human and rodent models. Endocr. Metab. Immune. Disord. Drug Targets, 8, 198-207.
6. Ford, E.S. (2005) Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care, 28, 1769-1778.
7. Malik, S.; Wong, N.D.; Franklin, S.S.; Kamath, T.V.; L'Italien, G.J.; Pio, J.R. and Williams, G.R. (2004) Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation, 110, 1245-1250.
8. Hoang, K.C.; Ghandehari, H.; Lopez, V.A.; Barboza, M.G. and Wong, N.D. (2008) Global coronary heart disease risk assessment of individuals with the metabolic syndrome in the U.S. Diabetes Care, 31, 1405-1409.
9. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. (2001) Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA, 285, 2486-2497.
10. Oliver MF. (1963) Further observations on the effect of Atromid and of ethyl chlorophenoxyisobutyrate on serum lipid levels. J. Atheroscler. Res., 3, 427-444.
11. Berkowitz, D. (1965) Effects of chlorophenoxyisobutyrate with and without androsterone on the serum lipids, fat tolerance and uric acid. Metabolism, 14, 966-975.
12. Reddy, J.K.; Goel, S.K.; Nemali, M.R.; Carrino, J.J.; Laffler, T.G.; Reddy, M.K.; Sperbeck, S.J.; Osumi, T.; Hashimoto, T.; Lalwani, N.D. and Rao, M.S. (1986) Transcription regulation of peroxisomal fatty acyl-CoA oxidase and enoyl-CoA hydratase:3-hydroxyacyl- CoA dehydrogenase in rat liver by peroxisome proliferators. Proc. Natl. Acad. Sci. USA, 83, 1747-1751.
13. Staels, B.; Van Tol, A.; Andreu, T. and Auwerx, J. (1992) Fibrates influence the expression of genes involved in lipoprotein metabolism in a tissue selective manner. Arterioscler. Thromb., 12, 286-294.
14. Staels, B.; Vu-Dac, N.; Kosykh, V.A.; Saladin, R.; Fruchart, J.C.; Dallongeville, J. and Auwerx, J. (1995) Fibrates downregulate apolipoprotein C-III expression independent of induction of peroxisomal acyl Coenzyme A oxidase. J. Clin. Invest., 95, 705-712.
15. Tugwood, J.D.; Issemann, I.; Anderson, R.G.; Bundell, K.R.; McPheat, W.L. and Green, S. (1992) The mouse peroxisome proliferator activated receptor recognizes a response element in the 5% flanking sequence of the rat acyl CoA oxidase gene. EMBO J., 11, 433-439.
16. Keller, H.; Dreyer, C.; Medin, J.; Mahfoudi, A.; Ozato, K. and Wahli, W. (1993) Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferatoractivated receptor- retinoid X receptor heterodimers. Proc. Natl. Acad. Sci. USA, 90, 2160-2164.
17. Gebel, T.; Arand, M. and Oesch, F. (1992) Induction of the peroxisome proliferator activated receptor by fenofibrate in rat liver. FEBS Lett., 309, 37-40.
18. Lee, S.S.T.; Pineau, T.; Drago, J.; Lee, E.J.; Owens, J.W.; Kroetz, D.L.; Fernandez-Salguero, P.M.; Westphal, H. and Gonzalez, F. (1995) Targeted disruption of the a isoform of the peroxisome proliferator- activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol. Cell. Biol., 15, 3012-3022.
19. Edgar, A.D.; Tomkiewicz, C.; Costet, P.; Legendre, C.; Aggerbeck, M.; Bouguet, J.; Staels, B.; Guyomard, C.; Pineau, T. and Barouki, R. (1998) Fenofibrate modifies transaminase gene expression via a peroxisome proliferator activated receptor 􀀁-dependent pathway. Toxicology Lett., 98, 13-23.
20. Chapman, M.J. (1987) Pharmacology of fenofibrate. Am. J. Med., 83, 21-25.
21. Guay, D.R.P. (1999) Micronized fenofibrate: a new fibric acid hypolipidemic agent. Ann. Pharmacother., 33, 1083-1103.
22. Huttunen, J.; Manninen, V.; Manttari, M.; Koskinen, P.; Romo, M.; Tenkanen, L.; Heinonen, O. and Frick, M. (1991) The Helsinki Heart Study: central findings and clinical implications. Ann. Med., 23, 155-159.
23. Rubins, H.B.; Robins, S.J.; Collins, D.; Fye, C.L.; Anderson, J.W.; Elam, M.B.; Faas, F.H.; Linares, E.; Schaefer, E.J.; Schectman, G.; Wilt, T.J. and Wittes, J. (1999) Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of highdensity lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N. Engl. J. Med., 341, 410-418.
24. Stamm, A. and Pawan, S. (1998) Fenofibrate pharmaceutical composition having high bioavailability and method for preparing it. Patent US6074670.
25. Guivarc'h, P.H.; Vachon, M.G. and Fordyce, D. (2004) A new fenofibrate formulation: results of six single-dose, clinical studies of bioavailability under fed and fasting conditions. Clin. Ther., 26, 1456-1469.
26. Sauron, R.; Wilkins, M.; Jessent, V.; Dubois, A.; Maillot, C. and Weil, A. (2006)Absence of a food effect with a 145 mg nanoparticle fenofibrate tablet formulation. Int. J. Clin. Pharmacol. Ther., 44, 64-70.
27. Djoussé, L.; Padilla, H.; Nelson, T.L.; Gaziano, J.M. and Mukamal, K.J. (2010) Diet and metabolic syndrome. Endocr. Metab. Immune. Disord. Drug Targets, 10, 124-137.
28. Devroey, D.; Vantomme, K.; Betz, W.; Vandevoorde, J. and Kartounian, J. (2004) A review of the treatment guidelines on the management of low levels of high-density lipoprotein cholesterol. Cardiology, 102, 61-66.
29. Keating, G.M. and Croom, K.F. (2007) Fenofibrate: a review of its use in primary dyslipidaemia, the metabolic syndrome and type 2 diabetes mellitus. Drugs, 67, 121-153.
30. Goldenberg, I.; Benderly, M. and Goldbourt, U. (2008) BIP Study Group. Secondary prevention with bezafibrate therapy for the treatment of dyslipidemia: an extended follow-up of the BIP trial. J. Am. Coll. Cardiol., 51, 459-465.
31. Birjmohun, R.S.; Hutten, B.A.; Kastelein, J.J. and Stroes, E.S. (2005) Efficacy and safety of high-density lipoprotein cholesterolincreasing compounds: a meta-analysis of randomized controlled trials. J. Am. Coll. Cardiol., 45, 185-197.
32. Farnier, M.; Roth, E.; Gil-Extremera, B.; Mendez, G.F.; Macdonell, G.; Hamlin, C.; Perevozskaya, I.; Davies, M.J.; Kush, D.; Mitchel, Y.B. and Ezetimibe/Simvastatin + Fenofibrate Study Group. (2007) Efficacy and safety of the coadministration of ezetimibe/ simvastatin with fenofibrate in patients with mixed hyperlipidemia. Am. Heart J., 153, 335.e1-e8.
33. Feher, M.D.; Caslake, M.; Foxton, J.; Cox, A. and Packard, C.J. (1999) Atherogenic lipoprotein phenotype in type 2 diabetes: reversal with micronised fenofibrate. Diabetes Metab. Res. Rev., 15, 395-399.
34. Franceschini, G.; Calabresi, L.; Colombo, C.; Favari, E.; Bernini, F. and Sirtori, C.R. (2007) Effects of fenofibrate and simvastatin on HDL-related biomarkers in low-HDL patients. Atherosclerosis, 195, 385-391.
35. Wang, T.D.; Chen, W.J.; Lin, J.W.; Cheng, C.C.; Chen, M.F. and Lee, Y.T. (2003) Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles. Atherosclerosis, 170, 315-323.
36. Rosenson, R.S. (2008) Fenofibrate reduces lipoprotein associated phospholipase A2 mass and oxidative lipids in hypertriglyceridemic subjects with the metabolic syndrome. Am. Heart J., 155, 499.e9-e16.
37. Arca, M.; Montali, A.; Pigna, G.; Antonini, R.; Antonini, T.M.; Luigi, P.; Fraioli, A.; Mastrantoni, M.; Maddaloni, M. and Letizia, C. (2007) Comparison of atorvastatin versus fenofibrate in reaching lipid targets and influencing biomarkers of endothelial damage in patients with familial combined hyperlipidemia. Metabolism, 56, 1534-1541.
38. Davidson, M.H.; Bays, H.E.; Stein, E.; Maki, K.C.; Shalwitz, R.A.; Doyle, R. and TRIMS Investigators. (2006) Effects of fenofibrate on atherogenic dyslipidemia in hypertriglyceridemic subjects. Clin. Cardiol., 29, 268-273.
39. Filippatos, T.D.; Liberopoulos, E.N.; Kostapanos, M.; Gazi, I.F.; Papavasiliou, E.C.; Kiortsis, D.N.; Tselepis, A.D. and Elisaf, M.S. (2008) The effects of orlistat and fenofibrate, alone or in combination, on high-density lipoprotein subfractions and pre-beta1-HDL levels in obese patients with metabolic syndrome. Diabetes Obes. Metab., 10, 476-483.
40. Hiukka, A.; Leinonen, E.; Jauhiainen, M.; Sundvall, J.; Ehnholm, C.; Keech, A.C.; Taskinen, M.R. (2007) Long-term effects of fenofibrate on VLDL and HDL subspecies in participants with type 2 diabetes mellitus. Diabetologia, 50, 2067-2075.
41. Ryan, K.E.; McCance, D.R.; Powell, L.; McMahon, R. and Trimble, E.R. (2007) Fenofibrate and pioglitazone improve endothelial function and reduce arterial stiffness in obese glucose tolerant men. Atherosclerosis, 194, e123-e130.
42. Zhu, S.; Su, G. and Meng, Q.H. (2006) Inhibitory effects of micronized fenofibrate on carotid atherosclerosis in patients with essential hypertension. Clin. Chem., 52, 2036-2042.
43. Undas, A.; Celinska-Löwenhoff, M.; Domagala, T.B.; Iwaniec, T.; Dropinski, J.; Löwenhoff, T. and Szczeklik, A. (2005) Early antithrombotic and anti-inflammatory effects of simvastatin versus fenofibrate in patients with hypercholesterolemia. Thromb. Haemost., 94, 193-199.
44. Ducobu, J.; VanHaelst, L. and Salomon, H. (2003) Comparison of micronized fenofibrate and pravastatin in patients with primary hyperlipidemia. J. Cardiovasc. Pharmacol., 41, 60-67.
45. Vega, G.L.; Cater, N.B.; Hadizadeh, III D.R.; Meguro, S. and Grundy, S.M. (2003) Free fatty acid metabolism during fenofibrate treatment of the metabolic syndrome. Clin. Pharmacol. Ther., 74, 236-244.
46. Scott, R.; O'Brien, R.; Fulcher, G.; Pardy, C.; D'Emden, M.; Tse, D.; Taskinen, M.R.; Ehnholm, C. and Keech, A. (2009) Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study Investigators. Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetes Care, 32, 493-498.
47. Keech, A.; Simes, R.J.; Barter, P.; Best, J.; Scott, R.; Taskinen, M.R.; Forder, P.; Pillai, A.; Davis, T.; Glasziou, P.; Drury, P.; Kesäniemi, Y.A.; Sullivan, D.; Hunt, D.; Colman, P.; d'Emden, M.; Whiting, M.; Ehnholm, C.; Laakso, M. and FIELD study investigators. (2005) Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): Randomized controlled trial. Lancet, 366, 1849-1861.
48. Vergès, B. (2006) Fenofibrate therapy and cardiovascular protection in diabetes: recommendations after FIELD. Curr. Opin. Lipidol., 17, 653-658.
49. Backes, J.M.; Gibson, C.A.; Ruisinger, J.F. and Moriarty, P.M. (2007) Fibrates: what have we learned in the past 40 years? Pharmacotherapy, 27, 412-424.
50. Balfour, J.A.; McTavish, D. and Heel, R.C. (1990) Fenofibrate, a review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in dyslipidemia. Drugs, 40, 260-290.
51. Haffner, S.M. and Ashraf, T. (2000) Predicting risk reduction of coronary disease in patients who are glucose intolerant: a comparison of treatment with fenofibrate and other lipid-modifying agents. Manag. Care Interface, 13, 52-58.
52. UK HDL-C Consensus Group. (2004) Role of fibrates in reducing coronary risk: a UK consensus. Curr. Med. Res. Opin., 20, 241-247.
53. Evans, M.; Roberts, A.; Davies, S. and Rees, A. (2004) Medical lipid-regulating therapy: current evidence, ongoing trials and future developments. Drugs, 64, 1181-1196.
54. Baigent, C.; Keech, A.; Kearney, P.M.; Blackwell, L.; Buck, G.; Pollicino, C.; Kirby, A.; Sourjina, T.; Peto, R.; Collins, R.; Simes, R. and Cholesterol Treatment Trialists' (CTT) Collaborators. (2005) Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet, 366, 1267-1278.
55. McKenney, J.M.; Davidson, M.H.; Jacobson, T.A.; Guyton, J.R. and National Lipid Association Statin Safety Task Force Liver Expert Panel. (2006) Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am. J. Cardiol., 97(8A), 89C-94C.
56. Steinberg, D. (2006) Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy, part V: the discovery of the statins and the end of the controversy. J. Lipid Res., 47, 1339-1351.
57. Davidson, M.H. and Robinson, J.G. (2006) Lipid-lowering effects of statins: a comparative review. Expert Opin. Pharmacother., 7, 1701-1714.
58. Wang, T.D.; Chen, W.J.; Lin, J.W.; Cheng, C.C.; Chen, M.F. and Lee, Y.T. (2003) Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles. Atherosclerosis, 170, 315-323.
59. Derosa, G.; Cicero, A.E.; Bertone, G.; Piccinni, M.N.; Ciccarelli, L.; Roggeri, D.E. (2004) Comparison of fluvastatin + fenofibrate combination therapy and fluvastatin monotherapy in the treatment of combined hyperlipidemia, type 2 diabetes mellitus, and coronary heart disease: a 12-month, randomized, double-blind, controlled trial. Clin. Ther., 26, 1599-1607.
60. Farnier, M.; Freeman, M.W.; Macdonell, G.; Perevozskaya, I.; Davies, M.J.; Mitchel, Y.B.; Gumbiner, B. and Ezetimibe Study Group. (2005) Efficacy and safety of the coadministration of ezetimibe with fenofibrate in patients with mixed hyperlipidaemia. Eur. Heart J., 26, 897-905.
61. Jones, P.H.; Bays, H.E.; Davidson, M.H.; Kelly, M.T.; Buttler, S.M.; Setze, C.M.; Sleep, D.J. and Stolzenbach, J.C. (2008) Evaluation of a new formulation of fenofibric acid, ABT-335, coadministered with statins: study design and rationale of a phase III clinical programme. Clin. Drug Investig., 28, 625-634.
62. Keech, A.C.; Mitchell, P.; Summanen, P.A.; O'Day, J.; Davis, T.M.; Moffitt, M.S.; Taskinen, M.R.; Simes, R.J.; Tse, D.; Williamson, E.; Merrifield, A.; Laatikainen, L.T.; d'Emden, M.C.; Crimet, D.C.; O'Connell, R.L.; Colman, P.G. and FIELD study investigators. (2007) Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomized controlled trial. Lancet, 2007, 370, 1687-1697.
63. Tomlinson, B.; Chan, P. and Lan, W. (2001) How well tolerated are lipid-lowering drugs? Drugs Aging, 18, 665-683.
64. Bellosta, S.; Paoletti, R. and Corsini, A. (2004) Safety of statins: Focus on clinical pharmacokinetics and drug interactions. Circulation, 109(23 Suppl 1), III50-III57.
65. Jones, P.H. and Davidson, M.H. (2005) Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin. Am. J. Cardiol., 95, 120-122.
66. Grundy, S.M.; Vega, G.L.; Yuan, Z.; Battisti, W.P.; Brady, W.E. and Palmisano, J. (2005) Effectiveness and tolerability of simvastatin plus fenofibrate for combined hyperlipidemia (the SAFARI trial). Am. J. Cardiol., 95, 462-468.
67. Fiévet, C. and Staels, B. (2009) Combination therapy of statins and fibrates in the management of cardiovascular risk. Curr. Opin. Lipidol., 20, 505-511.
68. Davidson, M.H. (2006) Statin/fibrate combination in patients with metabolic syndrome or diabetes: evaluating the risks of pharmacokinetic drug interactions. Expert Opin. Drug Saf., 5, 145-156.
69. Gil-Extremera, B.; Mendez, G.; Zakson, M.; Meehan, A.; Shah, A.; Lin, J. and Mitchel, Y. (2007) Efficacy and safety of ezetimibe/simvastatin co- administered with fenofibrate in mixed hyperlipidemic patients with metabolic syndrome. Metab. Syndr. Relat. Disord., 5, 305-314.
70. Vakkilainen, J.; Steiner, G.; Ansquer, J.C.; Perttunen-Nio, H. and Taskinen, M.R. (2002) Fenofibrate lowers plasma triglycerides and increases LDL particle diameter in subjects with type 2 diabetes. Diabetes Care, 25, 627-628.
71. Lemieux, I.; Laperrière, L.; Dzavik, V.; Tremblay, G.; Bourgeois, J. and Després, J.P. (2002) A 16-week fenofibrate treatment increases LDL particle size in type IIA dyslipidemic patients. Atherosclerosis, 162, 363-371.
72. Rubins, H.B.; Robins, S.J.; Collins, D.; Fye, C.L.; Anderson, J.W.; Elam, M.B.; Faas, F.H.; Linares, E.; Schaefer, E.J.; Schectman, G.; Wilt, T.J.; Wittes, J. and for The Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. (1999) Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N. Engl. J. Med., 341, 410-418.
73. Rosenson, R.S.; Wolff, D.A.; Huskin, A.L.; Helenowski, I.B. and Rademaker, A.W. (2007) Fenofibrate therapy ameliorates fasting and postprandial lipoproteinemia, oxidative stress, and the inflammatory response in subjects with hypertriglyceridemia and the metabolic syndrome. Diabetes Care, 30:1945-1951.
74. Rubins, H.B.; Robins, S.J.; Collins, D.; Nelson, D.B.; Elam, M.B.; Schaefer, E.J.; Faas, F.H.; Anderson, J.W. and for the VA-HIT Study Group. (2002) Diabetes, Plasma Insulin, and Cardiovascular Disease: Subgroup Analysis From the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). Arch. Intern. Med., 162, 2597-2604.
75. Williams, R.R.; Skolnick, M.; Carmelli, D.; Maness, A.T.; Hunt, S.C.; Hasstedt, S.; Reiber, G.E. and Jones, R.K. (1979) Utah pedigree studies: design and preliminary data for premature male CHD deaths. Prog. Clin. Biol. Res., 32, 711-729.
76. Wilson, P.W.; D'Agostino, R.B.; Levy, D.; Belanger, A.M.; Silbershatz, H.; and Kannel, W.B. (1998) Prediction of coronary heart disease using risk factor categories. Circulation, 97, 1837-1847.
77. Tuomilehto, J. (2003) Reducing coronary heart disease associated with type 2 diabetes: lifestyle intervention and treatment of dyslipidaemia. Diabetes Res. Clin. Pract., 61, S27-34.
78. Wierzbicki, A.S. (2009) Fibrates in the treatment of cardiovascular risk and atherogenic dyslipidaemia. Curr. Opin. Cardiol., 24, 372-379.
79. de Las Fuentes, L.; de Simone, G.; Arnett, D.K. and Dávila-Román, V.G. (2010) Molecular Determinants of the Cardiometabolic Phenotype. Endocr. Metab. Immune. Disord. Drug Targets, 10, 109-123.
80. Barbier, O.; Torra, I.P.; Duguay, Y.; Blanquart, C.; Fruchart, J.C.; Glineur, C. and Staels, B. (2002) Pleiotropic actions of peroxisome proliferator-activated receptors in lipid metabolism and atherosclerosis. Arterioscler. Thromb. Vasc. Biol., 22, 717-726.
81. Mandard, S.; Muller, M. and Kersten, S. (2004) Peroxisome proliferator- activated receptor 􀀁 target genes. Cell Mol. Life Sci., 61, 393-416.
82. Schoonjans, K.; Staels, B. and Auwerx, J. (1996) The peroxisome proliferator activated receptors (PPARs) and their effects on lipid metabolism and adipocyte differentiation. Biochim. Biophys. Acta., 1302, 93-109.
83. Grundy, S.M. and Vega, G.L. (1987) Fibric acids: effects on lipids and lipoprotein metabolism. Am. J. Med., 83, 9-20.
84. WHO cooperative trial on primary prevention of ischaemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up. (1984) Report of the Committee of Principal Investigators. Lancet, 2, 600-604.
85. Tenkanen, L.; Mänttäri, M.; Kovanen, P.T.; Virkkunen, H. and Manninen, V. (2006) Gemfibrozil in the treatment of dyslipidemia: an 18-year mortality follow-up of the Helsinki Heart Study. Arch. Intern. Med., 166, 743-748.
86. Burgess, D.C.; Hunt, D.; Li, L.; Zannino, D.; Williamson, E.; Davis, T.M.; Laakso, M.; Kesäniemi, Y.A.; Zhang, J.; Sy, R.W.; Lehto, S.; Mann, S. and Keech, A.C. (2010) Incidence and predictors of silent myocardial infarction in type 2 diabetes and the effect of fenofibrate: an analysis from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Eur. Heart J., 31, 92-99.
87. Ansquer, J.C.; Foucher, C.; Aubonnet, P. and Le Malicot, K. (2009) Fibrates and microvascular complications in diabetes-- insight from the FIELD study. Curr. Pharm. Des., 15, 537-552.
88. Higgins, M.; Province, M.; Heiss, G.; Eckfeldt, J.; Ellison, R.C.; Folsom, A.R.; Rao, D.C.; Sprafka, J.M. and Williams, R. (1996) NHLBI Family Heart Study: objectives and design. Am. J. Epidemiol., 143, 1219-1228.
89. Arnett, D.K.; Miller, M.B.; Coon, H.; Ellison, R.C.; North, K.E.; Province, M.; Leppert, M. and Eckfeldt, J.H. (2004) Genome-wide linkage analysis replicates susceptibility locus for fasting plasma triglycerides: NHLBI Family Heart Study. Hum. Genet., 115, 468-474.
90. Rasmussen-Torvik, L.J.; Pankow, J.S.; Peacock, J.M.; Borecki, I.B.; Hixson, J.E.; Tsai, M.Y.; Kabagambe, E.K. and Arnett, D.K. (2009) Suggestion for linkage of chromosome 1p35.2 and 3q28 to plasma adiponectin concentrations in the GOLDN Study. BMC Med. Genet., 10, 39.
91. Liu, Y.; Ordovas, J.M.; Gao, G.; Province, M.; Straka, R.J.; Tsai, M.Y.; Lai, C.Q.; Zhang, K.; Borecki, I.; Hixson, J.E.; Allison, D.B. and Arnett, D.K. (2008) The SCARB1 gene is associated with lipid response to dietary and pharmacological interventions. J. Hum Genet., 53, 709-717.
92. Shen, J.; Arnett, D.K.; Parnell, L.D.; Peacock, J.M.; Lai, C.Q.; Hixson, J.E.; Tsai, M.Y.; Province, M.A.; Straka, R.J. and Ordovas, J.M. (2008) Association of common C-reactive protein (CRP) gene polymorphisms with baseline plasma CRP levels and fenofibrate response: the GOLDN study. Diabetes Care, 31, 910-915.
93. Smith, J.A.; Arnett, D.K.; Kelly, R.J.; Ordovas, J.M.; Sun, Y.V.; Hopkins, P.N.; Hixson, J.E.; Straka, R.J.; Peacock, J.M. and Kardia, S.L. (2008) The genetic architecture of fasting plasma triglyceride response to fenofibrate treatment. Eur. J. Hum. Genet., 16, 603-613.
94. Lai, C.Q.; Arnett, D.K.; Corella, D.; Straka, R.J.; Tsai, M.Y.; Peacock, J.M.; Adiconis, X.; Parnell, L.D.; Hixson, J.E.; Province, M.A. and Ordovas, J.M. (2007) Fenofibrate effect on triglyceride and postprandial response of apolipoprotein A5 variants: the GOLDN study. Arterioscler. Thromb. Vasc. Biol., 27, 1417-1425.
95. Kraja, A.T.; Hunt, S.C.; Pankow, J.S.; Myers, R.H.; Heiss, G.; Lewis, C.E.; Rao, D.C. and Province, M.A. (2005) Quantitative trait loci for metabolic syndrome in the hypertension genetic epidemiology network study. Obes. Res., 13, 1885-1890.
96. Ahituv, N.; Akiyama, J.; Chapman-Helleboid, A.; Fruchart, J. and Pennacchio, L.A. (2007) In vivo characterization of human APOA5 haplotypes. Genomics, 90, 674-679.
97. Lai, C.Q.; Demissie, S.; Cupples, L.A.; Zhu, Y.; Adiconis, X.; Parnell, L.D.; Corella, D. and Ordovas, J.M. (2004) Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study. J. Lipid Res., 45, 2096-2105.
98. Pennacchio, L.A.; Olivier, M.; Hubacek, J.A.; Cohen, J.C.; Cox, D.R.; Fruchart, J.C.; Krauss, R.M.; Rubin, E.M. (2001) An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science, 294, 169-173.
99. Qi, L.; Liu, S.; Rifai, N.; Hunter, D. and Hu, F.B. (2007) Associations of the apolipoprotein A1/C3/A4/A5 gene cluster with triglyceride and HDL cholesterol levels in women with type 2 diabetes. Atherosclerosis, 192, 204-210.
100. Willer, C.J.; Sanna, S.; Jackson, A.U.; Scuteri, A.; Bonnycastle, L.L.; Clarke, R.; Heath, S.C.; Timpson, N.J.; Najjar, S.S.; Stringham, H.M.; Strait, J.; Duren, W.L.; Maschio, A.; Busonero, F.; Mulas, A.; Albai, G.; Swift, A.J.; Morken, M.A.; Narisu, N.; Bennett, D.; Parish, S.; Shen, H.; Galan, P.; Meneton, P.; Hercberg, S.; Zelenika, D.; Chen, W.M.; Li, Y.; Scott, L.J.; Scheet, P.A.; Sundvall, J.; Watanabe, R.M.; Nagaraja, R.; Ebrahim, S.; Lawlor, D.A.; Ben-Shlomo, Y.; Davey-Smith, G.; Shuldiner, A.R.; Collins, R.; Bergman, R.N.; Uda, M.; Tuomilehto, J.; Cao, A.; Collins, F.S.; Lakatta, E.; Lathrop, G.M.; Boehnke, M.; Schlessinger, D.; Mohlke, K.L. and Abecasis, G.R. (2008) Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet., 40, 161-169.
101. Diep, Q.N.; Benkirane, K.; Amiri, F.; Cohn, J.S.; Endemann, D. and Schiffrin, E.L. (2004) PPAR alpha activator fenofibrate inhibits myocardial inflammation and fibrosis in angiotensin II-infused rats. J. Mol. Cell Cardiol., 36, 295-304.
102. Goya, K.; Sumitani, S.; Xu, X.; Kitamura, T.; Yamamoto, H.; Kurebayashi, S.; Saito, H.; Kouhara, H.; Kasayama, S. and Kawase, I. (2004) Peroxisome proliferator-activated receptor alpha agonists increase nitric oxide synthase expression in vascular endothelial cells. Arterioscler. Thromb. Vasc. Biol., 24, 658-663.
103. Maitland-van der Zee, A.H.; Turner, S.T.; Schwartz, G.L.; Chapman, A.B.; Klungel, O.H. and Boerwinkle, E. (2005) A multilocus approach to the antihypertensive pharmacogenetics of hydrochlorothiazide. Pharmacogenet. Genomics, 15, 287-293.
104. Möllsten, A.; Wessman, M.; Svensson, M.; Forsblom, C.; Parkkonen, M.; Brismar, K.; Groop, P.H. and Dahlquist, G. (2006) Glu298Asp and NOS4ab polymorphisms in diabetic nephropathy. Ann. Med., 38, 522-528.
105. Mitchell, G.F.; Guo, C.Y.; Kathiresan, S.; Vasan, R.S.; Larson, M.G.; Vita, J.A.; Keyes, M.J.; Vyas, M.; Newton-Cheh, C.; Musone, S.L.; Camargo, A.L.; Drake, J.A.; Levy, D.; O'Donnell, C.J.; Hirschhorn, J.N. and Benjamin, E.J. (2007) Vascular stiffness and genetic variation at the endothelial nitric oxide synthase locus: the Framingham Heart study. Hypertension, 49, 1285-1290.
106. Otsuki, M.; Goya, K. and Kasayama, S. (2005) Vascular endothelium as a target of beraprost sodium and fenofibrate for antiatherosclerotic therapy in type 2 diabetes mellitus. Vasc. Health Risk Manag., 1, 209-215.
107. Blanco-Rivero, J.; Márquez-Rodas, I.; Xavier, F.E.; Aras-López, R.; Arroyo-Villa, I.; Ferrer, M. and Balfagón, G. (2007) Long-term fenofibrate treatment impairs endothelium-dependent dilation to acetylcholine by altering the cyclooxygenase pathway. Cardiovasc. Res., 75, 398-407.
108. The NAVIGATOR Study Group. (2010) Effect of Valsartan on the Incidence of Diabetes and Cardiovascular Events. N. Engl. J. Med., [Epub ahead of print].
109. Kenward, M.G. and Roger, J.H. (1997) Small sample inference for fixed effects from restricted maximum likelihood. Biometrics., 53, 983-997.