American Journal of Cardiology
Volume 102, Issue 10, Supplement , Pages 1K-34K , 17 November 2008

The Residual Risk Reduction Initiative: A Call to Action to Reduce Residual Vascular Risk in Patients with Dyslipidemia

  • Jean-Charles Fruchart, PhD (Co-Chair)

      Affiliations

    • INSERM UR 545, Institut Pasteur de Lille, Université Lille 2, Lille, France
    • Corresponding Author InformationAddress for reprints: Jean-Charles Fruchart, PhD, Laboratoire J & K, Inserm UR 545, Faculté de Médecine de Lille, Pôle Recherche, Boulevard du Professeur Leclerc, 59045 Lille Cedex, France
  • ,
  • Frank Sacks, MD (Co-Chair)

      Affiliations

    • Nutrition Department, Harvard School of Public Health, Department of Medicine, Harvard Medical School, and Cardiovascular Division and Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts, USA
  • ,
  • Michel P. Hermans, MD, PhD (General Secretary)

      Affiliations

    • Cliniques Universitaires St-Luc, Service d'Endocrinologie et Nutrition, Brussels, Belgium
  • ,
  • Gerd Assmann, MD

      Affiliations

    • Assmann-Stiftung für Prävention, Münster, Germany
  • ,
  • W. Virgil Brown, MD

      Affiliations

    • Emory University School of Medicine and Veterans Affairs Medical Center, Decatur, Georgia, USA
  • ,
  • Richard Ceska, MD, PhD

      Affiliations

    • Center of Preventive Cardiology, University General Hospital, Prague, Czech Republic
  • ,
  • M. John Chapman, PhD, DSc

      Affiliations

    • Dyslipidemia and Atherosclerosis Research Unit, INSERM U.551, Hôpital de la Pitié, Paris, France
  • ,
  • Paul M. Dodson, MD

      Affiliations

    • Medical Ophthalmology, and Diabetes, Heart of England Foundation Trust, Birmingham, UK
  • ,
  • Paola Fioretto, MD

      Affiliations

    • Department of Medical and Surgical Sciences, University of Padova, Padova, Italy
  • ,
  • Henry N. Ginsberg, MD

      Affiliations

    • Department of Medicine and Irving Institute for Clinical and Translational Research, Columbia University, New York, New York, USA
  • ,
  • Takashi Kadowaki, MD

      Affiliations

    • Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
  • ,
  • Jean-Marc Lablanche, MD

      Affiliations

    • Service de Cardiologie B et Hémodynamique, Hôpital Cardiologique, Lille, France
  • ,
  • Nikolaus Marx, MD

      Affiliations

    • Department of Internal Medicine II, University of Ulm, Ulm, Germany
  • ,
  • Jorge Plutzky, MD

      Affiliations

    • Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
  • ,
  • Željko Reiner, MD, PhD

      Affiliations

    • University Hospital Center Zagreb, Zagreb, Croatia
  • ,
  • Robert S. Rosenson, MD

      Affiliations

    • Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA
  • ,
  • Bart Staels, PhD

      Affiliations

    • INSERM UR 545, Institut Pasteur de Lille, Université Lille 2, Lille, France
  • ,
  • Jane K. Stock, PhD

      Affiliations

    • London, UK
  • ,
  • Rody Sy, MD

      Affiliations

    • Lipid Research Unit, Department of Medicine, University of the Philippines-Philippine General Hospital, Manila, Philippines
  • ,
  • Christoph Wanner, MD

      Affiliations

    • Department of Medicine, Division of Nephrology, University Hospital Würzburg, Würzburg, Germany
  • ,
  • Alberto Zambon, MD, PhD

      Affiliations

    • Department of Medical and Surgical Sciences, University of Padova, Padova, Italy
  • ,
  • Paul Zimmet, MD, PhD

      Affiliations

    • International Diabetes Institute, Caulfield, Victoria, Australia
  • ,
  • Residual Risk Reduction Initiative (R3i)

      Affiliations

    • The Residual Risk Reduction Initiative (R3i) is an independent body of basic and clinical scientists, cardiologists, endocrinologists and diabetologists that has been formed to address this issue. It is registered in Switzerland under its legal jurisdiction. This will ensure that the scientists will set the direction and have control of the activities of the R3i. The current funders are Solvay Pharmaceuticals.

References 

  1. Booth GL, Kapral MK, Fung K, Tu JV. Recent trends in cardiovascular complications among men and women with and without diabetes. Diabetes Care. 2006;29:32–37
  2. Häussler B, Schiffhorst G, Gothe H, Hempel E. The impact of pharmaceuticals on the decline of cardiovascular mortality in Germany. Pharmacoepidemiol Drug Saf. 2007;16:1167–1176
  3. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). 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) (Final report). Circulation. 2002;106:3143–3421
  4. American Diabetes Association. Standards of medical care in diabetes-2008. Diabetes Care. 2008;31(suppl 1):S12–S54
  5. Smith SC, Allen J, Blair SN, Bonow RO, Brass LW, Fonarow GC, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation. 2006;113:2363–2372
  6. Buse JB, Ginsberg HN, Bakris GL, Clark NG, Costa F, Eckel R, et al Primary prevention of cardiovascular diseases in people with diabetes mellitus: a Scientific Statement from the American Heart Association and the American Diabetes Association. Circulation. 2007;115:114–126
  7. Graham I, Atar D, Borch-Johnsen K, Boysen G, Burell G, Cifkova R, et al European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Eur Heart J. 2007;28:2375–2414
  8. Rydén L, Standl E, Bartnik M, Van den Berghe G, Betteridge J, de Boer M-J, et al Guidelines on diabetes, pre-diabetes, and cardiovascular disease: executive summary. Eur Heart J. 2007;28:88–136
  9. Gregg EW, Gu Q, Cheng YJ, Narayan KM, Cowie CC. Mortality trends in men and women with diabetes, 1971–2000. Ann Intern Med. 2007;147:149–155
  10. Lipscombe LL, Hux JE. Trends in diabetes prevalence, incidence, and mortality in Ontario, Canada 1995–2005: a population-based study. Lancet. 2007;369:750–756
  11. Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001;414:782–787
  12. O'Flaherty M, Ford E, Allender S, Scarborough P, Capewell S. Coronary heart disease trends in England and Wales from 1984 to 2004; concealed levelling of mortality rates among young adults. Heart. 2008;94:178–181
  13. Ford ES, Capewell S. Coronary heart disease mortality among young adults in the U.S. from 1980 through 2002: concealed leveling of mortality rates. J Am Coll Cardiol. 2007;50:2128–2132
  14. Fox CS, Coady S, Sorlie PD, D'Agostino RB, Pencina MV, Vasan RS, et al. Increasing cardiovascular disease burden due to diabetes mellitus: the Framingham Heart Study. Circulation. 2007;115:1544–1550
  15. Leibson CL, Williamson DF, Melton LJ, Palumbo PJ, Smith SA, Ransom JE, et al. Temporal trends in BMI among adults with diabetes. Diabetes Care. 2001;24:1584–1589
  16. Murray CJ, Lopez AD. Regional patterns of disability-free life expectancy and disability-adjusted life expectancy: Global Burden of Disease Study. Lancet. 1997;349:1347–1352
  17. Ho PM, Magid DJ, Shetterly SM, Olson KL, Peterson PN, Masoudi FA, et al. Importance of therapy intensification and medication nonadherence for blood pressure control in patients with coronary disease. Arch Intern Med. 2008;168:271–276
  18. UKPDS. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33): UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837–853
  19. UKPDS report number 38 (Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes). BMJ. 1998;317:703–713
  20. Stratton IM, Cull CA, Adler AI, Matthews DR, Neil HA, Holman RR. Additive effects of glycaemia and blood pressure exposure on risk of complications in type 2 diabetes: a prospective observational study (UKPDS 75). Diabetologia. 2006;49:1761–1769
  21. Kemp TM, Barr ELM, Zimmet PZ, Cameron AJ, Wellborn TA, Colagiuri S, et al. Glucose, lipid, and blood pressure control in Australian adults with type 2 diabetes: the 1999–2000 AusDiab. Diabetes Care. 2005;28:1490–1492
  22. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348:383–393
  23. Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358:580–591
  24. The Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383–1389
  25. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;335:1001–1009
  26. The Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349–1357
  27. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7–22
  28. Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, et al Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:1623–1630
  29. Sever PSS, Dahlöf B, Poulter N, Wedel H, Beevers G, Caufield M, et al Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361:1149–1158
  30. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack (ALLHAT-LLT). JAMA. 2002;288:2998–3007
  31. Knopp RH, D'Emden M, Smilde JG, Pocock SJ. Efficacy and safety of atorvastatin in the prevention of cardiovascular endpoints in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN). Diabetes Care. 2006;29:1478–1485
  32. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995;333:1301–1307
  33. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA. 1998;279:1615–1622
  34. Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364:685–696
  35. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–1278
  36. Kearney PM, Blackwell PM, Collins R, Keech A, Simes J, Peto R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371:117–125
  37. Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227–239Erratum in: Circulation 2004;110:763
  38. Brunzell JD, Davidson M, Furberg CD, Goldberg RB, Howard BV, Stein JH, et al. Lipoprotein management in patients with cardiometabolic risk: consensus statement from the American Diabetes Association and the American College of Cardiology Foundation. Diabetes Care. 2008;31:811–822
  39. LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352:1425–1435
  40. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495–1504
  41. Centers for Disease Control and Prevention (CDC), National Diabetes-Surveillance System. Diabetes data and trends. CDC Web site http://www.cdc.gov/diabetes/statistics/prev/national/figpersons.htmAccessed June 2008
  42. International Diabetes Federation. E-Atlas. 2005. Accessed June 2008 http://www.eatlas.idf.org
  43. American Diabetes Association. Economic consequences of diabetes mellitus in the U.S. in 1997: American Diabetes Association. Diabetes Care. 1998;21:296–309
  44. American Diabetes Association. Economic costs of diabetes in the U.S. in 2007. Diabetes Care. 2008;31:596–615
  45. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937–952
  46. Austin MA, King MC, Vranizan KM, Krauss RM. Atherogenic lipoprotein phenotype: a proposed genetic marker for coronary heart disease risk. Circulation. 1990;82:495–506
  47. Ninomiya JK, L'Italien G, Criqui MH, Whyte JL, Gamst A, Chen RS. Association of the metabolic syndrome with history of myocardial infarction and stroke in the Third National Health and Nutrition Examination Survey. Circulation. 2004;109:42–46
  48. Alsheikh-Ali AA, Lin J-L, Abourjaily P, Ahearn D, Kuvin JT, Karas JH. Prevalence of low high-density lipoprotein cholesterol in patients with documented coronary heart disease or risk equivalent and controlled low-density lipoprotein cholesterol. Am J Cardiol. 2007;100:1499–1501
  49. Assmann G, Schulte H, Cullen P, Seedorf U. Assessing risk of myocardial infarction and stroke: new data from the Prospective Cardiovascular Münster (PROCAM) study. Eur J Clin Invest. 2007;37:925–932
  50. Austin MA, Hokanson JE, Edwards KL. Hypertriglyceridemia as a cardiovascular risk factor. Am J Cardiol. 1998;81(suppl):7B–12B
  51. Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S, et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2007;115:450–458
  52. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;297:299–308
  53. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA. 2007;298:309–316
  54. Assmann G, Schulte H, Seedorf U. Cardiovascular risk assessment in the metabolic syndrome: results from the Prospective Cardiovascular Münster (PROCAM) study. Int J Obes. 2008;32:S11–S16
  55. Sniderman A, Vu H, Cianflone K. Effect of moderate hypertriglyceridemia on the relation of plasma total and LDL apo B levels. Atherosclerosis. 1991;89:109–116
  56. St. Pierre AC, Cantin B, Dagenais GR, Mauriege P, Bernard PM, Despres JP, et al. Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Québec Cardiovascular Study. Arterioscler Thromb Vasc Biol. 2005;25:553–559
  57. Walldius G, Jungner I, Holme I, Aastveit AH, Kolar W, Steiner E. High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet. 2001;358:2026–2033
  58. Shai I, Rimm EB, Hankinson SE, Curhan G, Manson JE, Rifai N, et al. Multivariate assessment of lipid parameters as predictors of coronary heart disease among postmenopausal women: potential implications for clinical guidelines. Circulation. 2004;110:2824–2830
  59. Jiang R, Schulze MB, Li T, Rifai N, Stampfer MJ, Rimm EB, et al. Non-HDL cholesterol and apolipoprotein B predict cardiovascular disease events among men with type 2 diabetes. Diabetes Care. 2004;27:1991–1997
  60. Pischon T, Girman CJ, Sacks FM, Rifai N, Stampfer MJ, Rimm EB. Non-high-density lipoprotein cholesterol and apolipoprotein B in the prediction of coronary heart disease in men. Circulation. 2005;112:3375–3383
  61. Gotto AM, Whitney E, Stein EA, Shapiro DR, Clearfield M, Weis S, et al. Relation between baseline and on-treatment lipid parameters and first acute major coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Circulation. 2000;101:477–484
  62. Simes RJ, Marschner IC, Hunt D, Colquhoun D, Sullivan D, Stewart RA, et al. Relationship between lipid levels and clinical outcomes in the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) trial: to what extent is the reduction in coronary events with pravastatin explained by on-study lipid levels?. Circulation. 2002;105:1162–1169
  63. van Lennep JE, Westerveld HT, Van Lennep HW, Zwinderman AH, Erkelens DW, van der Wall EE. Apolipoprotein concentrations during treatment and recurrent coronary artery disease events. Arterioscler Thromb Vasc Biol. 2000;20:2408–2413
  64. Kathiresan S, Otvos JD, Sullivan LM, Keyes MJ, Schaefer EJ, Wilson PW, et al. Increased small low-density lipoprotein particle number: a prominent feature of the metabolic syndrome in the Framingham Heart Study. Circulation. 2006;113:20–29
  65. Vega GL, Grundy SM. Occurrence of species of low-density lipoprotein with defective clearance in patients with primary moderate hypercholesterolaemia. J Intern Med. 1992;232:405–413
  66. Alaupovic P, Mack W, Knight-Gibson C, Hodis HN. The role of triglyceride-rich lipoprotein families in the progression of atherosclerotic lesions as determined by sequential coronary angiography from a controlled clinical trial. Arterioscler Thromb Vasc Biol. 1997;17:715–722
  67. Sacks FM, Alaupovic P, Moye LA, Cole TG, Sussex B, Stampfer MJ, et al. Very low density lipoproteins, apolipoproteins B, CIII, and E and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial. Circulation. 2000;102:1886–1892
  68. Lee SJ, Campos H, Moye LA, Sacks FM. LDL containing apolipoprotein CIII is an independent risk factor for coronary events in diabetic patients. Arterioscler Thromb Vasc Biol. 2003;23:853–858
  69. Chivot L, Mainard F, Bigot E, Bard JM, Auget JL, Madec Y, et al. Logistic discriminant analysis of lipids and apolipoproteins in a population of coronary bypass patients and the significance of apolipoproteins CIII and E. Atherosclerosis. 1990;82:205–211
  70. Luc G, Fievet C, Arveiler D, Evans E, Bard JM, Cambien F, et al. Apolipoproteins CIII and E in apoB- and non-apoB-containing lipoproteins in two populations at contrasting risk for myocardial infarction: the ECTIM study. J Lipid Res. 1996;7:508–517
  71. Blankenhorn DH, Alaupovic P, Wickham E, Chin HP, Azen SP. Prediction of angiographic change in native human coronary arteries and aortocoronary bypass grafts. Circulation. 1990;81:470–476
  72. Hodis HN, Mack WJ, Azen JP, Alaupovic P, Pogoda JM, Labree L, et al. Triglyceride- and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin. Circulation. 1994;90:42–49
  73. Olivieri O, Bassi A, Stranieri C, Trabetti E, Martinelli N, Pizzolo F, et al. Apolipoprotein C-III, metabolic syndrome, and risk of coronary artery disease. J Lipid Res. 2003;44:2374–2381
  74. Onat A, Hergenc G, Sansoy V, Fobker M, Ceyhan K, Toprak S, et al. Apolipoprotein C-III, a strong discriminant of coronary risk in men and a determinant of the metabolic syndrome in both genders. Atherosclerosis. 2003;168:81–89
  75. Zheng CY, Khoo C, Ikewaki K, Sacks FM. Rapid turnover of apolipoprotein CIII containing triglyceride-rich lipoproteins contributing to formation of LDL subfractions. J Lipid Res. 2007;48:1190–1203
  76. Chan DC, Watts GF, Nguyen MN, Barrett PH. Apolipoproteins C-III and A-V as predictors of very-low-density lipoprotein triglyceride and apolipoprotein B-100 kinetics. Arterioscler Thromb Vasc Biol. 2006;26:590–596
  77. Kawakami A, Aikawa M, Libby P, Alcaide P, Luscinskas FW, Sacks FM. Apolipoprotein CIII in apolipoprotein B lipoproteins enhances the adhesion of human monocytic cells to endothelial cells. Circulation. 2006;113:691–700
  78. Kawakami A, Aikawa M, Alcaide P, Luscinskas FW, Libby P, Sacks FM. Apolipoprotein CIII induces expression of vascular cell adhesion molecule-1 in vascular endothelial cells and increases adhesion of monocytic cells. Circulation. 2006;114:681–687
  79. Cohn JS, Patterson BW, Uffelman KD, Davignon J, Steiner G. Rate of production of plasma and very-low-density lipoprotein (VLDL) apolipoprotein C-III is strongly related to the concentration and level of production of VLDL triglyceride in male subjects with different body weights and levels of insulin sensitivity. J Clin Endocrinol Metab. 2004;89:3949–3955
  80. Campos H, Perlov D, Khoo C, Sacks FM. Distinct patterns of lipoproteins with apoB defined by presence of apoE or apoC-III in hypercholesterolemia and hypertriglyceridemia. J Lipid Res. 2001;42:1239–1249
  81. Juntti-Berggren L, Refai E, Appelskog I, Andersson M, Imreh G, Dekki N, et al Apolipoprotein CIII promotes Ca2+-dependent beta cell death in type 1 diabetes. Proc Natl Acad Sci U S A. 2004;101:10090–10094
  82. Chen M, Breslow JL, Li W, Leff T. Transcriptional regulation of the apoC-III gene by insulin in diabetic mice: correlation with changes in plasma triglyceride levels. J Lipid Res. 1994;35:1918–1924
  83. Klein RL, McHenry MB, Lok KH, Hunter SJ, Le NA, Jenkins AJ, et al. Apolipoprotein CIII protein concentrations and gene polymorphisms in Type 1 diabetes: associations with microvascular disease complications in the DCCT/EDIC cohort. J Diabetes Complications. 2005;19:18–25
  84. Birjmohun RS, Dallinga-Thie GM, Kuivenhoven JA, Stroes ES, Otvos JD, Wareham NJ, et al. Apolipoprotein A-II is inversely associated with risk of future coronary artery disease. Circulation. 2007;116:2029–2035
  85. Stampfer MJ, Sacks FM, Salvini S, Willett WC, Hennekens CH. A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction. N Engl J Med. 1991;325:373–381
  86. Ballantyne CM, Olsson AG, Cook TJ, Mercuri MF, Pedersen TR, Kjekshus J. Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S. Circulation. 2001;104:3046–3051
  87. Barter PJ, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357:1301–1310
  88. Miller M, Cannon CP, Murphy SA, Qin J, Ray KK, Braunwald E PROVE-IT TIMI 22 Investigators. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE-IT TIMI 22 trial. J Am Coll Cardiol. 2008;51:724–730
  89. Jenkins AJ, Rowley KG, Lyons TJ, Best JD, Hill MA, Klein RL. Lipoproteins and diabetic microvascular complications. Curr Pharm Des. 2004;10:3395–3418
  90. Chew EY, Klein ML, Ferris FL, Remaley NA, Murphy RP, Chantry K, et al. Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy: Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22. Arch Ophthalmol. 1996;114:1079–1084
  91. Ucgun NI, Yildirim Z, Kilic N, Gϋrsel E. The importance of serum lipids in exudative diabetic macular edema in type 2 diabetic patients. Ann N Y Acad Sci. 2007;100:213–217
  92. Chowdhury TA, Hopkins D, Dodson PM, Vafidis GC. The role of serum lipids in exudative diabetic maculopathy: is there a place for lipid-lowering therapy?. Eye. 2002;16:689–693
  93. Davis MD, Fisher MR, Gangnon RE, Barton F, Aiello LM, Chew EY, et al. Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss (Early Treatment Diabetic Retinopathy Study Report 18). Invest Ophthalmol Vis Sci. 1998;39:233–252
  94. Lyons TJ, Jenkins AJ, Zheng D, Lackland DT, McGee D, Garvey WT, et al. Diabetic retinopathy and serum lipoprotein subclasses in the DCCT/EDIC cohort. Invest Ophthalmol Vis Sci. 2004;45:910–918
  95. Caramori ML, Fioretto P, Mauer M. The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient?. Diabetes. 2000;49:1399–1408
  96. Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR UKPDS Study Group. Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74. Diabetes. 2006;55:1832–1839
  97. Hadjadj S, Duly-Bouhanick B, Bekherraz A, Bridoux F, Gallois Y, Mauco G, et al. Serum triglycerides are a predictive factor for the development and the progression of renal and retinal complications in patients with type 1 diabetes. Diabetes Metab. 2004;30:43–51
  98. Cusick M, Chew EY, Hoogwerf B, Agron E, Wu L, Lindley A, et al. Risk factors for renal replacement therapy in the Early Treatment Diabetic Retinopathy Study (ETDRS): ETDRS 26. Kidney Int. 2004;66:1173–1179
  99. Smulders Y, Rakic M, Stehouwer C, Weijers RN, Slaats EH, Silberbusch J. Determinants of progression of microalbuminuria in patients with NIDDM: a prospective study. Diabetes Care. 1997;20:999–1005
  100. Chaturvedi N, Fuller JH, Taskinen MR EURODIAB PCS Group. Differing associations of lipid and lipoprotein disturbances with the macrovascular and microvascular complications of type 1 diabetes. Diabetes Care. 2001;24:2071–2077
  101. Jenkins AJ, Lyons TJ, Zheng D, Otvos JD, Lackland DT, McGee D, et al. Lipoproteins in the DCCT/EDIC Research Group: associations with diabetic nephropathy. Kidney Int. 2003;64:817–828
  102. Molitch ME, Rupp D, Carnethon M. Higher levels of HDL cholesterol are associated with a decreased likelihood of albuminuria in patients with long-standing type 1 diabetes. Diabetes Care. 2006;29:78–82
  103. Tesfaye S, Chaturvedi N, Eaton SE, Ward JD, Manes C, Ionescu-Tirogoviste C, et al. Vascular risk factors and diabetic neuropathy. N Engl J Med. 2005;352:341–350
  104. Kempler P, Tesfaye S, Chaturvedi N, Stevens LK, Webb DJ, Eaton S, et al. Autonomic neuropathy is associated with increased cardiovascular risk factors: the EURODIAB IDDM Complications Study. Diabet Med. 2002;19:900–909
  105. Diabetes Prevention Program Research Group. The prevalence of retinopathy in impaired glucose tolerance and recent-onset diabetes in the Diabetes Prevention Program. Diabet Med. 2007;24:137–144
  106. Delerive P, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors in inflammation control. J Endocrinol. 2001;169:453–459
  107. Fruchart JC, Duriez P, Staels B. Peroxisome proliferator-activated receptor-α activators regulate genes governing lipoprotein metabolism, vascular inflammation and atherosclerosis. Curr Opin Lipidol. 1999;10:245–257
  108. Dichtl W, Nilsson L, Goncalves I, Ares MP, Banfi C, Calara F, et al. Very low-density lipoprotein activates nuclear factor-κB in endothelial cells. Circ Res. 1999;84:1085–1094
  109. Kawakami A, Aikawa M, Nitta N, Yoshida M, Libby P, Sacks FM. Apolipoprotein CIII-induced cell adhesion to endothelial cells involves pertussis toxin-sensitive G-protein kinase Ca-mediated nuclear factor-κB activation. Arterioscler Thromb Vasc Biol. 2007;27:219–225
  110. Ting HJ, Stice JP, Schaff UY, Hui DY, Rutledge JC, Knowlton AA, et al. Triglyceride-rich lipoproteins prime aortic endothelium for inflammatory responses to TNF-α. Circ Res. 2007;100:381–390
  111. Marx N, Duez H, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells. Circ Res. 2004;94:1168–1178
  112. Pettersson C, Fogelstrand L, Rosengren B, Stahlman S, Hurt-Camejo E, Fagerberg B, et al. Increased lipolysis by secretory phospholipase A2 group V of lipoproteins in diabetic dyslipidaemia. J Intern Med. 2008;264:155–165
  113. Kontush A, Chapman MJ. Functionally defective high-density lipoprotein: a new therapeutic target at the crossroads of dyslipidaemia, inflammation, and atherosclerosis. Pharmacol Rev. 2006;58:342–374
  114. De Souza JA, Vindis C, Hansel B, Negre-Salvayre A, Therond P, Cerrano CV, et al. Metabolic syndrome features small, apolipoprotein A-I-poor, triglyceride-rich HDL3 particles with defective anti-apoptotic activity. Atherosclerosis. 2008;197:84–94
  115. Brown JD, Plutzky J. Peroxisome proliferator-activated receptors as transcriptional nodal points and therapeutic targets. Circulation. 2007;115:518–533
  116. Mason RP. Molecular basis of differences among statins and a comparison with antioxidant vitamin. Am J Cardiol. 2006;98(suppl 1):34P–41P
  117. Ray KK, Cannon CP, Ganz P. Beyond lipid lowering: what have we learned about the benefits of statins from the acute coronary syndromes trials?. Am J Cardiol. 2006;98(suppl):18P–25P
  118. Rosenson RS, Tangney CC. Antiatherothrombotic properties of statins. JAMA. 1998;279:1643–1650
  119. Trichopoulou A, Costacou T, Barnia C, Trichopoulous D. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med. 2003;348:2599–2608
  120. Trichopoulou A, Barnia C, Trichopoulous D. Mediterranean diet and survival among patients with coronary heart disease in Greece. Arch Intern Med. 2005;165:929–935
  121. Giugliano D, Esposito K. Mediterranean diet and metabolic diseases. Curr Opin Lipidol. 2008;19:63–68
  122. McKellar G, Morrison E, McEntegart A, Hampson R, Tierney A, Mackle G, et al. A pilot study of a Mediterranean-type diet intervention in female patients with rheumatoid arthritis living in areas of social deprivation in Glasgow. Ann Rheum Dis. 2007;66:1239–1243
  123. Gao X, Chen H, Fung TT, Logroscino G, Schwarzschild MA, Hu FB, et al. Prospective study of dietary patterns and risk of Parkinson disease. Am J Clin Nutr. 2007;86:1486–1494
  124. Scarmeas N, Luchsinger JA, Mayeux R, Stern Y. Mediterranean diet and Alzheimer disease mortality. Neurology. 2007;69:1084–1093
  125. Trichopoulou A, Kouris-Blazos A, Wahlqvist ML, Gnardellis C, Lagiou P, Polychronopoulos E, et al. Diet and overall survival in the elderly. BMJ. 1995;311:1457–1460
  126. Esposito K, Marfella R, Ciotola M, Di Palo C, Giugliano F, D'Armiento M, et al. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome. JAMA. 2004;292:1440–1446
  127. Appel LJ, Sacks FM, Carey VJ, Obarzanek E, Swain JF, Miller ER, et al. Effects of protein, monosaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial. JAMA. 2005;294:2455–2464
  128. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. N Engl J Med. 2001;344:3–10
  129. Schaefer EJ, Gleason JA, Dansinger ML. The effects of low-fat, high-carbohydrate diets on plasma lipoproteins, weight loss, and heart disease risk reduction. Curr Atheroscler Rep. 2005;7:421–427
  130. Brousseau ME, Schaefer EJ. Diet and coronary heart disease: clinical trials. Curr Atheroscler Rep. 2000;2:487–493
  131. Parikh P, McDaniel MC, Ashen MD, Miller JI, Sorrentino M, Chan V, et al. Diets and cardiovascular disease: an evidence-based assessment. J Am Coll Cardiol. 2005;45:1379–1387
  132. De Lorgeril M, Renaud S, Mamelle N, Salen P, Martin JL, Monjaud I, et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet. 1994;343:1454–1459
  133. GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet. 1999;354:447–455
  134. Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, Di Mascio R, et al Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infartio miocardico (GISSI)-Prevenzione. Circulation. 2002;105:1897–1903
  135. Mensink RP, Zock PL, Kester AD, Katan MB. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr. 2003;77:1146–1155
  136. Garg A. High-monounsaturated fat diet for diabetic patients: is it time to change the current dietary recommendations?. Diabetes Care. 1994;17:242–246
  137. Covas MI, Nyyssonen K, Poulsen HE, Kaikkonen J, Zunft HJ, Kiesewetter H, et al The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial. Ann Intern Med. 2006;145:333–341
  138. Laaksonen DE, Nyyssönen K, Niskanen L, Rissanen TH, Salonen JT. Prediction of cardiovascular mortality in middle-aged men by dietary and serum linoleic and polyunsaturated fatty acids. Arch Intern Med. 2005;165:193–199
  139. Campos H, Baylin A, Willett WC. Alpha linolenic acid and risk of nonfatal myocardial infarction. Circulation. 2008;118:339–344
  140. Forsythe CE, Phinney SD, Fernandez ML, Quann EE, Wood RJ, Bibus DM, et al. Comparison of low fat and low carbohydrate diets on circulating fatty acid composition and markers of inflammation. Lipids. 2008;43:65–77
  141. Bassuk SS, Manson JE. Epidemiological evidence for the role of physical activity in reducing risk of type 2 diabetes and cardiovascular disease. J Appl Physiol. 2005;99:1193–1204
  142. Joen CY, Lokken RP, Hu FB, Van Dam RM. Physical activity of moderate intensity and risk of type 2 diabetes: a systematic review. Diabetes Care. 2007;30:744–752
  143. Trichopoulou A, Psaltopoulou T, Orfanos P, Trichopoulos D. Diet and physical activity in relation to overall mortality amongst adults diabetics in a general population cohort. J Intern Med. 2006;259:583–591
  144. Weinstein AR, Sesso HD, Lee IM, Rexrode KM, Cook NR, Manson JE, et al. The joint effects of physical activity and body mass index on coronary heart disease risk in women. Arch Intern Med. 2008;168:884–890
  145. DeFronzo RA, Sherwin RS, Kraemer N. Effect of physical training on insulin action in obesity. Diabetes. 1987;36:1379–1385
  146. Thomas DE, Elliott EJ, Naughton GA. Exercise for type 2 diabetes mellitus. Cochrane Database System Rev. 2006;3:CD002968
  147. Sigal RJ, Kenny GP, Boule NG, Wells GA, Prud'homme D, Fortier M, et al. Effects of aerobic training, resistance training or both on glycaemic control in type 2 diabetes: a randomized trial. Ann Intern Med. 2007;147:357–369
  148. Kraus WE, Houmard JA, Duscha BD, Knetzger KJ, Wharton MB, McCartney JS, et al. Effects of the amount and intensity of exercise on plasma lipoproteins. N Engl J Med. 2002;347:1483–1492
  149. Kodama S, Tanaka S, Saito K, Shu M, Sone Y, Onitake F, et al. Effect of aerobic exercise training on serum lipid levels of high density lipoprotein cholesterol: a meta-analysis. Arch Intern Med. 2007;167:999–1008
  150. Kelley GA, Kelley KS, Tran ZV. Exercise, lipids, and lipoproteins in older adults: a meta-analysis. Prev Cardiol. 2005;8:206–214
  151. Kelley GA, Kelley KS. Aerobic exercise and lipids and lipoproteins in children and adolescents: a meta-analysis of randomized controlled trials. Atherosclerosis. 2007;191:447–453
  152. Kelley GA, Kelley KS, Tran ZV. Walking, lipids, and lipoproteins: a meta-analysis of randomized controlled trials. Prev Med. 2004;38:651–661
  153. Stewart KJ, Bacher AC, Turner K, Lim JG, Hees PS, Shapiro EP, et al. Exercise and risk factors associated with metabolic syndrome in older adults. Am J Prev Med. 2005;28:9–18
  154. Duncan GE, Anton SD, Sydeman SJ, Newton RL, Corsica JA, Durning PE, et al. Prescribing exercise at varied levels of intensity and frequency: a randomized trial. Arch Intern Med. 2005;165:2362–2369
  155. Laaksonen DE, Lindstrom J, Lakka TA, Eriksson JG, Niskanen L, Wikstrom K, et al Physical activity in the prevention of type 2 diabetes: the Finnish diabetes prevention study. Diabetes. 2005;54:158–165
  156. Johnson JL, Slenz CA, Houmard JA, Samsa GP, Duscha BD, Aiken LB, et al. Exercise training amount and intensity effects on metabolic syndrome (from studies of a targeted risk reduction intervention through defined exercise). Am J Cardiol. 2007;100:1759–1766
  157. Chiuve SE, McCullough ML, Sacks FM, Rimm EB. Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and antihypertensive medications. Circulation. 2006;114:160–167
  158. Pourcet B, Fruchart J-C, Staels B, Glineur C. Selective PPAR modulators, dual and pan PPAR agonists: multimodal drugs for the treatment of type 2 diabetes and atherosclerosis. Expert Opin Emerg Drugs. 2006;11:379–401
  159. Gross B, Staels B. PPAR agonists: multimodal drugs for the treatment of type-2 diabetes. Best Pract Res Clin Endocrinol Metab. 2007;21:687–710
  160. Staels B, Fruchart JC. Therapeutic roles of peroxisome proliferator-activated receptor agonists. Diabetes. 2005;54:2460–2470
  161. Duez H, Lefebvre B, Poulain P, Torra IP, Percevault F, Luc G, et al Regulation of human apo A-I by gemfibrozil and fenofibrate through selective PPARα modulation. Arterioscler Thromb Vasc Biol. 2005;25:585–589
  162. Chapman MJ. Fibrates in 2003: therapeutic action in atherogenic dyslipidaemia and future perspectives. Atherosclerosis. 2003;171:1–13
  163. Feher MD, Caslake M, Foxton J, Cox A, Packard CJ. Atherogenic lipoprotein phenotype in type 2 diabetes: reversal with micronised fenofibrate. Diabetes Metab Res Rev. 1999;15:395–399
  164. Vakkilainen J, Steiner G, Ansquer JC, Aubin F, Rattier S, Foucher C, et al. Relationships between low-density lipoprotein particle size, plasma lipoproteins, and progression of coronary artery disease: the Diabetes Atherosclerosis Study (DAIS). Circulation. 2003;107:1733–1737
  165. Rosenson RS, Wolff DA, Huskin AL, Helenowski IB, Rademaker RW. Fenofibrate therapy ameliorates fasting and postprandial lipoproteinemia, oxidative stress, and the inflammatory response in subjects with hypertriglyceridemia and the metabolic syndrome. Diabetes Care. 2007;30:1945–1951
  166. Ruotolo G, Ericsson CG, Tettamanti C, Karpe F, Grip L, Svane B, 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). J Am Coll Cardiol. 1998;32:1648–1656
  167. Robins SJ, Collins D, Wittes JT, Papademetriou V, Deedwania PC, Schaefer EJ, et al. Veterans Affairs High-Density Lipoprotein Intervention Trial (Relation of gemfibrozil treatment and lipid levels with major coronary events. VA-HIT: a randomized controlled trial). JAMA. 2001;285:1585–1591
  168. Hiukka A, Leinonen E, Jauhiainen M, Sundvall J, Ehnholm C, Keech AC, et al. Long-term effects of fenofibrate on VLDL and HDL subspecies in participants with type 2 diabetes. Diabetologia. 2007;50:2067–2075
  169. May HT, Anderson JL, Pearson RR, Jensen JR, Horne BD, Lavasani F, et al. Comparison of effects of simvastatin alone versus fenofibrate alone versus simvastatin plus fenofibrate on lipoprotein subparticle profiles in diabetic patients with mixed dyslipidemia (from the Diabetes and Combined Lipid Therapy Regimen Study). Am J Cardiol. 2008;101:486–489
  170. Asztalos BF, Collins D, Horvarth KV, Bloomfield HE, Robins SJ, Schaefer EJ. Relation of gemfibrozil treatment and high-density lipoprotein subpopulation profile with cardiovascular events in the Veterans Affairs High-Density Lipoprotein Intervention Trial. Metabolism. 2008;57:77–83
  171. Ooi TC, Cousins M, Ooi DS, Nakajima K, Edwards AL. Effect of fibrates on postprandial remnant-like particles in patients with combined hyperlipidemia. Atherosclerosis. 2004;172:375–382
  172. Rosenson RS, Huskin AL, Wolff DA, Helenowski IB, Rademaker AW. Fenofibrate reduces fasting and postprandial inflammatory responses among hypertriglyceridemia patients with the metabolic syndrome. Atherosclerosis. 2008;198:381–388
  173. Ooi TC, Heinonen T, Alaupovic P, Davignon J, Leiter L, Lupien PJ, et al. Efficacy and safety of a new HMG CoA reductase inhibitor, atorvastatin, in patients with combined hyperlipidemia: comparison with fenofibrate. Arterioscler Thromb Vasc Biol. 1997;17:1793–1799
  174. Lamendola C, Abbasi F, Chu JW, Hutchinson H, Cain V, Leary E, et al. Comparative effects of rosuvastatin and gemfibrozil on glucose, insulin, and lipid metabolism in insulin-resistant, nondiabetic patients with combined dyslipidemia. Am J Cardiol. 2005;95:189–193
  175. Wagner JA, Larson PJ, Weiss S, Miller JL, Doebber TW, Wu MS, et al. Individual and combined effects of peroxisome proliferator-activated receptor and γ agonists, fenofibrate and rosiglitazone, on biomarkers of lipid and glucose metabolism in healthy nondiabetic volunteers. J Clin Pharmacol. 2005;45:504–513
  176. Davidson MH, Bays HE, Stein E, Maki KC, Shalwitz RA, Doyle R. Effects of fenofibrate on atherogenic dyslipidemia in hypertriglyceridemic subjects. Clin Cardiol. 2006;29:268–273
  177. Sacks FM, Alaupovic P, Moye LA. Effect of pravastatin on apolipoproteins B and C-III in very-low-density lipoproteins and low-density lipoproteins. Am J Cardiol. 2002;90:165–167
  178. Alaupovic P, Heinonen T, Shurzinske L, Black DM. Effect of a new HMGCoA reductase inhibitor, atorvastatin, on lipids, apolipoproteins and lipoprotein particles in patients with elevated serum cholesterol and triglyceride levels. Atherosclerosis. 1997;133:123–133
  179. Ballantyne CM, Herd JA, Ferlic LL, Dunn JK, Farmer JA, Jones PH, et al. Influence of low HDL on progression of coronary artery disease and response to fluvastatin therapy. Circulation. 1999;99:736–743
  180. Han SH, Quon MJ, Koh KK. Beneficial vascular and metabolic effects of peroxisome proliferatoractivated receptor-α activators. Hypertension. 2005;46:1086–1092
  181. Zambon A, Gervois P, Pauletto P, Fruchart JC, Staels B. Modulation of hepatic inflammatory risk markers of cardiovascular diseases by PPAR-α activators: clinical and experimental evidence. Arterioscler Thromb Vasc Biol. 2006;26:977–986
  182. Muhlestein JB, May HT, Jensen JR, Horne BD, Lanman RB, Lavasani F, et al. The reduction of inflammatory biomarkers by statin, fibrate, and combination therapy among diabetic patients with mixed dyslipidemia: the DIACOR (Diabetes and Combined Lipid Therapy Regimen) study. J Am Coll Cardiol. 2006;48:396–401
  183. Koh K, Quon MJ, Han SH, Chung WJ, Ahn JY, Seo YH, et al. Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia. J Am Coll Cardiol. 2005;45:1649–1653
  184. Aguilar-Salinas CA, Lerman-Garber I, Perez J, Villa AR, Martinez CL, Turrubiatez LC, et al. Ciprofibrate versus gemfibrozil in the treatment of mixed hyperlipidemias: an open-label, multicenter study. Metabolism. 2001;50:729–733
  185. Lalloyer F, Vandewalle B, Percevault F, Torpier G, Kerr-Conte J, Oosterveer M, et al. Peroxisome proliferator-activated receptor α improves pancreatic adaptation to insulin resistance in obese mice and reduces lipotoxicity in human islets. Diabetes. 2006;55:1605–1613
  186. The DREAM Trial Investigators. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006;368:1096–1105
  187. Orasanu G, Ziouzenkova O, Devchand PR, Nehra V, Hamdy O, Horton ES, et al. The peroxisome proliferator-activated receptor-γ agonist pioglitazone represses inflammation in a peroxisome proliferator-activated receptor-α-dependent manner in vitro and in vivo in mice. J Am Coll Cardiol. 2008;52:869–881
  188. Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med. 1999;341:410–418
  189. Rubins HB, Robins SJ, Collins D, Nelson DB, Elam MB, Schaefer EJ, et al. Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT). Arch Intern Med. 2002;162:2597–2604
  190. The BIP Study group. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. Circulation. 2000;102:21–27
  191. Tenenbaum A, Motro M, Fisman EZ, Tanne D, Boyko V, Behar S. Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome. Arch Intern Med. 2005;165:1154–1160
  192. Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P, et al. Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia. N Engl J Med. 1987;317:1237–1245
  193. Manninen V, Tenkanen L, Koskinen P, Huttunen JK, Mantarri M, Heinonen OP, et al. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study: implications for treatment. Circulation. 1992;85:37–45
  194. Keech A, Simes RJ, Barter P, Best J, Scott J, Taskinen MR, et al Effect of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366:1849–1861
  195. Scott R, d'Emden M, Best J, Drury P, Ehnholm C, Kesaniemi A, et al. Features of metabolic syndrome identify individuals with type 2 diabetes mellitus at high risk for cardiovascular events and greater absolute benefits of fenofibrate. Circulation. 2007;116:II_838;Abstract 3691
  196. Robins SJ, Rubins HB, Faas FH, Schaefer EJ, Elam MB, Anderson JW, et al. Insulin resistance and cardiovascular events with low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT). Diabetes Care. 2003;26:1513–1517
  197. Otvos JD, Collins D, Freedman DS, Shalaurova L, Schaefer EJ, McNamara JR, 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. 2006;113:1556–1563
  198. Tenkanen L, Mantarri M, Kovanen PT, Virkkunen H, Manninen V. Gemfibrozil in the treatment of dyslipidemia: an 18-year mortality follow-up of the Helsinki Heart Study. Arch Intern Med. 2006;166:743–748
  199. Keech A, Simes J, Barter P, Best J, Scott R, Taskinen MR FIELD Management Committee. Correction to the FIELD study report [letter]. Lancet. 2006;368:1415
  200. Frick MH, Syvanne M, Nieminen MS, Kauma H, Majahalme S, Virtanen V, et al. Prevention of the angiographic progression of coronary and vein graft atherosclerosis by gemfibrozil after coronary bypass surgery in men with low levels of HDL cholesterol. Circulation. 1997;96:2137–2143
  201. Ericsson CG, Hamsten A, Nilsson J, Grip L, Svane B, de Faire U. Angiographic assessment of effects of bezafibrate on progression of coronary artery disease in young male postinfarction patients. Lancet. 1996;347:849–853
  202. Diabetes Atherosclerosis Intervention Study Investigators. Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes; the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet. 2001;357:905–910
  203. Chinetti-Gbaguidi G, Fruchart JC, Staels B. Pleiotropic effects of fibrates. Curr Atheroscler Rep. 2005;7:396–401
  204. Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, et al Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial in macroVascular Events): a randomised controlled trial. Lancet. 2005;366:1279–1289
  205. Nissen SE, Nicholls SJ, Wolski K, Nesto R, Kupfer S, Perez A, et al Comparison of pioglitazone vs glimerpiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA. 2008;299:1561–1573
  206. Keating GM, Croom KF. Fenofibrate: a review of its use in primary dyslipidaemia, the metabolic syndrome and type 2 diabetes mellitus. Drugs. 2007;67:121–153
  207. Grundy SM, Vega GL, Yuan Z, Battisti WP, Brady WE, Palmisano J. Effectiveness and tolerability of simvastatin plus fenofibrate for combined hyperlipidemia (the SAFARI trial). Am J Cardiol. 2005;95:462–468
  208. Athyros VG, Papageorgiou AA, Athyrou VV, Demitriadis DS, Kontopoulos AG. Atorvastatin and micronized fenofibrate alone and in combination in type 2 diabetes with combined hyperlipidemia. Diabetes Care. 2002;25:1198–1202
  209. Alsheikh-Ali AA, Kuvin JT, Karas RH. Risk of adverse events with fibrates. Am J Cardiol. 2004;94:935–938
  210. Ballantyne CM, Corsini A, Davidson MH, Holdaas H, Jacobson TA, Leitersdorf E, et al. Risk of myopathy with statin therapy in high-risk patients. Arch Intern Med. 2003;163:553–564
  211. Rosenson RS. Current overview of statin-induced myopathy. Am J Med. 2004;116:408–416
  212. Jones PH, Davidson MH. Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin. Am J Cardiol. 2005;95:120–122
  213. Backman JT, Kyrklund C, Kivisto KT, Wang JS, Neuvonen PJ. Plasma concentrations of active simvastatin acid are increased by gemfibrozil. Clin Pharmacol Ther. 2000;68:122–129
  214. Kyrklund C, Backman JT, Neuvonen M, Neuvonen PJ. Gemfibrozil increases plasma pravastatin concentrations and reduces pravastatin renal clearance. Clin Pharmacol Ther. 2003;73:538–544
  215. Kyrklund C, Backman JT, Kivisto KT, Neuvonen M, Laitila J, Neuvonen PJ. Plasma concentrations of active lovastatin acid are markedly increased by gemfibrozil but not by bezafibrate. Clin Pharmacol Ther. 2001;69:340–345
  216. Schneck DW, Birmingham BK, Zalikowski JA, Mitchell PD, Wang Y, Martin PD, et al. The effect of gemfibrozil on the pharmacokinetics of rosuvastatin. Clin Pharmacol Ther. 2004;75:455–463
  217. Backman JT, Luurila H, Neuvonen M, Neuvonen PJ. Rifampicin markedly decreases and gemfibrozil increases the plasma concentrations of atorvastatin and its metabolites. Clin Pharmacol Ther. 2005;78:154–167
  218. Prueksaritanont T, Subramanian R, Fang X, Ma B, Qiu Y, Lin JH, et al. Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization. Drug Metab Dispos. 2002;30:505–512
  219. Prueksaritanont T, Tang C, Qiu Y, Mu L, Subramanian R, Lin JH. Effects of fibrates on metabolism of statins in human hepatocytes. Drug Metab Dispos. 2002;30:1280–1287
  220. Pan W, Gustavsson LE, Achari R, Rieser MJ, Ye X, Gutterman C, et al. Lack of clinically significant pharmacokinetic interaction between fenofibrate and pravastatin in healthy volunteers. J Clin Pharmacol. 2000;40:316–323
  221. Bergman AJ, Murphy G, Burke J, Zhao JJ, Valesky R, Liu L, et al Simvastatin does not have a clinically significant pharmacokinetic interaction with fenofibrate in humans. J Clin Pharmacol. 2004;44:1054–1062
  222. Gustavson LE, Schweitzer SM, Koehne-Voss S, Achari R, Chira TO, Esslinger HU, et al. The effects of multiple doses of fenofibrate on the pharmacokinetics of pravastatin and its 3α-hydroxy isomeric metabolite. J Clin Pharmacol. 2005;45:947–953
  223. Martin PD, Dane AL, Schneck DW, Warwick MJ. An open-label, randomized, three-way crossover trial of the effects of coadministration of rosuvastatin and fenofibrate on the pharmacokinetic properties of rosuvastatin and fenofibric acid in healthy male volunteers. Clin Ther. 2003;25:459–471
  224. Penn R, Williams RX, Guha-Ray DK, Sawyers WG, Braun SL, Rains KT. An open-label, cross-over study of the pharmacokinetics of Insoluble Drug Delivery MicroParticle fenofibrate in combination with atorvastatin, simvastatin and extended-release niacin in healthy volunteers. Clin Ther. 2006;28:45–54
  225. Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety considerations with fibrate therapy. Am J Cardiol. 2007;99(suppl):3C–18C
  226. Tonelli M, Collins D, Robins S, Bloomfield H, Curhan GC Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) Investigators. Gemfibrozil for secondary prevention of cardiovascular events in mild to moderate chronic renal insufficiency. Kidney Int. 2004;66:1123–1130
  227. Dierkes J, Westphal S, Luley C. The effect of fibrates and other lipid-lowering drugs on plasma homocysteine levels. Exp Opin Drug Saf. 2004;3:101–111
  228. Ford ES, Smith SJ, Stroup KK, Steinberg KK, Mueller PW, Thacker SB. Homocyst(e)ine and cardiovascular disease: a systematic review of the evidence with special emphasis on case-control studies and nested case-control studies. Int J Epidemiol. 2002;31:59–70
  229. Spence JD, Ban H, Chambless LE, Stampfer MJ. Vitamin Intervention for Stroke Prevention trial: an efficacy analysis. Stroke. 2005;36:2404–2409
  230. Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006;354:1578–1588
  231. The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354:1567–1577
  232. Ginsberg HN, Bonds D, Lovato LC, Crouse JR, Elam MB, Linz PE, et al. Evolution of the lipid trial protocol of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 1997;99(suppl):56i–67i
  233. Morgan JM, Capuzzi DM, Guyton JR, Centor RM, Goldberg R, Robbins DC, et al. Treatment effect of NIASPAN, a controlled-release niacin, in patients with hypercholesterolemia: a placebo-controlled trial. J Cardiovasc Pharmacol Ther. 1996;1:195–202
  234. Goldberg A, Alagona P, Capuzzi DM, Guyton J, Morgan JM, Rodgers J, et al. Multiple-dose efficacy and safety of an extended-release form of nicotinic acid in the management of hyperlipidemia. Am J Cardiol. 2000;85:1100–1105
  235. McCormack PL, Keating GM. Prolonged-release nicotinic acid: a review of its use in the treatment of dyslipidaemia. Drugs. 2005;65:2719–2740
  236. Morgan JM, Capuzzi DM, Baksh RI, Intenzo C, Carey CM, Reese D, et al. Effects of extended-release niacin on lipoprotein subclass distribution. Am J Cardiol. 2003;91:1432–1436
  237. Pan J, Lin M, Kesala RL, Van J, Charles MA. Niacin treatment of the atherogenic lipid profile and Lp(a) in diabetes. Diabetes Obes Metab. 2002;4:255–261
  238. Karpe F, Frayn KN. The nicotinic acid receptor – a new mechanism for an old drug. Lancet. 2004;363:1892–1894
  239. Soudijn W, van Wijngaarden I, Ijzerman AP. Nicotinic acid receptor subtypes and their ligands. Med Res Rev. 2007;27:417–433
  240. Wang W, Basinger A, Neese RA, Shane B, Myong SA, Christiansen M, et al. Effect of nicotinic acid administration on hepatic very low density lipoprotein-triglyceride production. Am J Physiol Endocrinol Metab. 2001;280:E540–E547
  241. Kamanna VS, Kashyap ML. Mechanism of action of niacin on lipoprotein metabolism. Curr Atheroscler Rep. 2000;2:36–46
  242. Shepherd J, Packard CJ, Patsch JR, Gotto AM, Taunton OD. Effect of nicotinic acid therapy on plasma high density lipoprotein subfraction distribution and composition and on apolipoprotein A metabolism. J Clin Invest. 1979;63:858–867
  243. Hernandez M, Wright SD, Cai TQ. Critical role of cholesterol ester transfer protein in nicotinic acid-mediated HDL elevation in mice. Biochem Biophys Res Commun. 2007;355:1075–1080
  244. Rosenson RS. Antiatherothrombotic effects of nicotinic acid. Atherosclerosis. 2003;171:87–96
  245. Coronary Drug Project Research Group. Clofibrate and niacin in coronary heart disease. JAMA. 1975;231:360–381
  246. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986;8:1245–1255
  247. Canner PL, Furberg CD, Terrin ML, McGovern ME. Benefits of niacin by glycemic status in patients with healed myocardial infarction (from the Coronary Drug Project). Am J Cardiol. 2005;95:254–257
  248. Brown G, Albers JJ, Fisher LD, Schaefer SM, Lin JT, Kaplan C, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990;323:1289–1298
  249. McKenney JM, Jones PH, Bays HE, Knopp RH, Kashyap ML, Ruoff GE, et al. Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study). Atherosclerosis. 2007;192:432–437
  250. Brown BG, Zhao XQ, Chait A, Fisher LD, Cheung MC, Morse JS, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345:1583–1592
  251. Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, Grace KA. Arterial Biology for the Investigation of the Treatment Effects of Reducing cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation. 2004;110:3512–3517
  252. Taylor AJ, Lee HJ, Sullenberger LE. The effect of 24-months of combination statin and extended-release niacin on carotid intima-media thickness (ARBITER 3). Curr Med Res Opin. 2006;22:2243–2250
  253. Rubenfire M Impact of Medical Subspecialty on Patient Compliance to Treatment Study Group. Safety and compliance with once-daily niacin extended-release/lovastatin as initial therapy in the Impact of Medical Subspecialty on Patient Compliance to Treatment (IMPACT) study. Am J Cardiol. 2004;94:306–311
  254. Brown G. Expert commentary: niacin safety. Am J Cardiol. 2007;99(suppl):32C–34C
  255. Guyton JR, Bays HE. Safety considerations with niacin therapy. Am J Cardiol. 2007;99(suppl):22C–31C
  256. Lai E, De Lepeleire I, Crumley TM, Liu F, Wenning LA, Michiels N, et al. Suppression of niacin-induced vasodilation with an antagonist to prostaglandin D2 receptor subtype1. Clin Pharmacol Ther. 2007;81:849–857
  257. Maccubbin D, Sirah W, Betteridge A. Lipid-altering efficacy and tolerability profile of extended release niacin/laropiprant in patients with primary hypercholesterolemia or mixed hyperlipidemia. Eur Heart J. 2007;28(suppl):108;Abstract P715
  258. Paolini JF, Mitchel YB, Reyes R, Kher U, Lai E, Watson DJ, et al. Effects of laropiprant on nicotinic acid-induced flushing in patients with dyslipidemia. Am J Cardiol. 2008;101:625–630
  259. Grundy SM, Vega GL, McGovern ME, Tulloch BP, Kendall DM, Fitz-Patrick D, et al. Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes: results of the Assessment of Diabetes Control and Evaluation of the Efficacy of Niaspan Trial. Arch Intern Med. 2002;162:1568–1576
  260. Ginsberg HN. Niacin in the metabolic syndrome: more risk than benefit?. Nature Clin Pract Endo Metab. 2006;2:2–3
  261. Clinical Trial. AIM HIGH: Niacin plus statin to prevent vascular events. Accessed June 5, 2008 http://www.clinicaltrials.gov./ct2/show/NCT00120289?term=NCT00120289&rank=1
  262. Clinical Trial Treatment of HDL to reduce the incidence of vascular events (HPS2-THRIVE). Accessed 5 June 2008 http://www.clinicaltrials.gov./ct2/show/NCT00461630?term=HPS2-THRIVE&rank=1
  263. Harris WS, Connor WE, Alam N, Illingworth DR. Reduction of postprandial triglyceridemia in humans by dietary n-3 fatty acids. J Lipid Res. 1988;29:1451–1460
  264. Harris WS. Omega-3 fatty acids and cardiovascular disease: a case for omega-3 index as a new risk factor. Pharmacol Res. 2007;55:217–223
  265. Montori VM, Farmer A, Wollan PC, Dinheen SF. Fish oil supplementation in type 2 diabetes: a quantitative systemic review. Diabetes Care. 2000;23:1407–1415
  266. Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? (A meta-analysis of controlled trials). Circulation. 1993;88:523–533
  267. Appel LJ, Miller ER, Seidler AJ, Whelton PK. Does supplementation of diet with ‘fish oil’ reduce blood pressure? (A meta-analysis of controlled clinical trials). Arch Intern Med. 1993;153:1429–1438
  268. Kris-Etherton PM, Harris WS, Appel LJ American Heart Association, Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106:2742–2757
  269. Sethi S, Ziouzenkova O, Ni H, Wagner DD, Plutzky J, Mayadas TN. Oxidized omega-3 fatty acids in fish oil inhibit leukocyte-endothelial interactions through activation of PPAR α. Blood. 2002;100:1340–1346
  270. Secondary prevention in primary and secondary care for patients following a myocardial infarction (Clinical guideline. May 2007. National Institute Health and Clinical Excellence). http://www.nice.org.uk/nicemedia/pdf/CG48NICEGuidance.pdfAccessed October 22, 2008
  271. Harris WS, Ginsberg HN, Arunakul N, Schachter NS, Windsor SL, Adams M, et al. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovasc Risk. 1997;4:385–391
  272. Davidson MH, Stein EA, Bays HE, Maki KC, Doyle RT, Shalwitz RA, et al. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007;29:1354–1367
  273. Durrington PN, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, et al. An omega-3-polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001;85:544–548
  274. Leaf A, Kang JX, Xiao YF. Omega-3 fatty acids and ventricular arrhythmias. World Rev Nutr Diet. 2005;94:129–138
  275. Leaf A. Omega-3 fatty acids and prevention of arrhythmias. Curr Opin Lipidol. 2007;18:31–34
  276. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomized open-label, blinded endpoint analysis. Lancet. 2007;369:1090–1098
  277. GISSI-HF Investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;published online on 29 August. Doi: 10.1016/S0140-6736(08)61239-8
  278. Morehouse LA, Sugarman ED, Bourassa PA, Sand TM, Zimetti F, Gao F, et al. Inhibition of CETP activity by torcetrapib reduces susceptibility to diet-induced atherosclerosis in New Zealand White rabbits. J Lipid Res. 2007;48:1263–1272
  279. Osono Y, Woollett LA, Marotti KR, Melchior GW, Dietschy JM. Centripetal cholesterol flux from extrahepatic organs to the liver is independent of the concentration of high density lipoprotein-cholesterol in plasma. Proc Natl Acad Sci U S A. 1996;93:4114–4119
  280. Boekholdt SM, Sacks FM, Jukema JW, Shepherd J, Freeman DJ, McMahon AD, et al Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment: individual patient meta-analysis of 13,677 subjects. Circulation. 2005;111:278–287
  281. Nagano M, Yamashita S, Hirano K, Takano M, Maruyama T, Ishihara M, et al Molecular mechanisms of cholesteryl ester transfer protein deficiency in Japanese. J Atheroscler Thromb. 2004;11:110–121
  282. Barzilai N, Atzmon G, Schechter EJ, Schaefer EJ, Cupples AL, Lipton R, et al. Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA. 2003;290:2030–2040
  283. Curb JD, Abbott RD, Rodriguez BL, Masaki K, Chen R, Sharp DS, et al. A prospective study of HDL-C and cholesteryl ester transfer protein gene mutations and the risk of coronary heart disease in the elderly. J Lipid Res. 2004;45:948–953
  284. Brousseau ME, O'Connor JJ, Ordovas JM, Collins D, Otvos JD, Massov T, et al. Cholesteryl ester transfer protein TaqI B2B2 genotype is associated with higher HDL cholesterol levels and lower risk of coronary heart disease end points in men with HDL deficiency: Veterans Affairs HDL Cholesterol Intervention Trial. Arterioscler Thromb Vasc Biol. 2002;22:1148–1154
  285. Barter P, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komadja M, et al. Effects of torcetrapib on morbidity and mortality in patients at high risk for coronary events. N Engl J Med. 2007;357:2109–2122
  286. Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT, et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med. 2007;356:1304–1316
  287. Kastelein JJP, van Leuven SI, Burgess L, Evans GW, Kuivenhoven JA, Barter PJ, et al. Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N Engl J Med. 2007;356:1620–1630
  288. Bots ML, Visseren FL, Evans GW, Riley WA, Revkin JH, Tegeler CH, et al. Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial. Lancet. 2007;370:153–160
  289. Krishna R, Anderson MS, Bergman AJ, Jin B, Fallon M, Cote J, et al Effect of the cholesteryl ester transfer protein inhibitor, anacetrapib, on lipoproteins in patients with dyslipidaemia and on 24-h ambulatory blood pressure in healthy individuals: two double-blind, randomised placebo-controlled phase I studies. Lancet. 2007;370:1907–1914
  290. Hollander P. Endocannabinoid blockade for improving glycemic control and lipids in patients with type 2 diabetes mellitus. Am J Med. 2007;120(suppl 1):S18–S28
  291. Scheen AJ, Finer N, Hollander P, Jensen MD, Van Gaal LF RIO-Diabetes Study Group. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet. 2006;368:1660–1672
  292. Despres JP, Golay A, Sjostrom L Rimonabant in Obesity-Lipids Study Group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005;353:2121–2134
  293. Henness S, Robinson DM, Lyseng-Williamson KA. Rimonabant. Drugs. 2006;66:2109–2119
  294. Van Gaal LF, Scheen AJ, Rissanen AM, Rossner S, Hanotin C, Ziegler O RIO-Europe Study Group. Long-term effect of CB1 blockade with rimonabant on cardiometabolic risk factors: two year results from the RIO-Europe Study. Eur Heart J. 2008;29:1761–1771
  295. Van Gaal L, Pi-Sunyer X, Despres JP, McCarthy C, Scheen A. Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: pooled 1-year data from the Rimonabant in Obesity (RIO) program. Diabetes Care. 2008;31(suppl 2):S229–S2240
  296. Nissen SE, Nicholls SJ, Wolski K, Rodes-Cabau J, Cannon CP, Deanfield JE, et al Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial. JAMA. 2008;299:1547–1560
  297. Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet. 2007;370:1706–1713
  298. Bell RA, Camacho F, Duren-Winfield VT, Bonds DE, Anderson RT, Konen JC, et al. Improving diabetes care among low-income North Carolinians: Project IDEAL. N C Med J. 2005;66:96–102
  299. Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, et al. Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy (A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes). Diabetologia. 2006;49:1711–1721
  300. American Diabetes Association. Nutrition recommendations and interventions for diabetes – 2006: a position statement of the American Diabetes Association. Diabetes Care. 2006;29:2140–2155
  301. The Advance Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–2572
  302. Patel A, MacMahon S, Chalmers J, Neal B, Woodward M, Billot L, et al Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370:829–840
  303. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–2559
  304. Sandhu S, Wiebe N, Fried LF, Tonelli M. Statins for improving renal outcomes: a meta-analysis. J Am Soc Nephrol. 2006;17:2006–2016
  305. Douglas K, O'Malley PG, Jackson JL. Meta-analysis: the effect of statins on albuminuria. Ann Intern Med. 2006;145:117–124
  306. HPS Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361:2005–2016
  307. Athyros VG, Mikhailidis DP, Papageorgiou AA, Symeonidis AN, Pehlivanidis AN, Bouloukos VI, et al. The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease: a subgroup analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study. J Clin Pathol. 2004;57:728–734
  308. Tonelli M, Isles C, Craven T, Tonkin A, Pfeffer MA, Shepherd J, et al Effect of pravstatin on rate of kidney function loss in people with or at risk for coronary disease. Circulation. 2005;112:171–178
  309. Shepherd J, Kastelein JJ, Bittner V, Deedwania P, Breazna A, Dobson S, et al. Effect of intensive lipid lowering with atorvastatin on renal function in patients with coronary heart disease: the Treating to New Targets (TNT) study. Clin J Am Soc Nephrol. 2007;2:1131–1139
  310. Campese VM, Park J. HMG-CoA reductase inhibitors and the kidney. Kidney Int. 2007;71:1215–1222
  311. Ansquer JC, Foucher C, Rattier S, Taskinen MR, Steiner G DAIS Investigators. Fenofibrate reduces progression to microalbuminuria over 3 years in a placebo-controlled study in type 2 diabetes: results from the Diabetes Atherosclerosis Intervention Study (DIAS). Am J Kidney Dis. 2005;45:485–493
  312. Dodson PM. Medical treatment for diabetic retinopathy: do the FIELD microvascular study results support a role for lipid lowering?. Practical Diabetes International. 2008;25:76–79
  313. Zhang J, McGwin G. Association of statin use with the risk of developing diabetic retinopathy. Arch Ophthalmol. 2007;125:1096–1099
  314. Gupta A, Gupta V, Thapar S, Bhansali A. Lipid-lowering drug atorvastatin as an adjunct in the management of diabetic macular edema. Am J Ophthalmol. 2004;137:675–682
  315. Keech AC, Mitchell P, Summanen PA, O'Day J, Davis TM, Moffitt MS, et al Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet. 2007;370:1687–1697
  316. Simó R, Hernández C. Fenofibrate for diabetic retinopathy. Lancet. 2007;370:1667–1668
  317. Cameron N, Cotter M, Inkster M, Nangle M. Looking to the future: diabetic neuropathy and effects of rosuvastatin on neuromuscular function. Diabetes Res Clin Pract. 2003;61(suppl 1):S35–S39
  318. Gulcan E, Gulcan A, Erbilen E, Toker S. Statins may be useful in diabetic foot ulceration treatment and prevention. Med Hypotheses. 2007;69:1313–1315
  319. Davis TM, Yeap BB, Davis WA, Bruce DG. Lipid-lowering therapy and peripheral sensory neuropathy in type 2 diabetes: the Fremantle Diabetes Study. Diabetologia. 2008;51:562–566
  320. Ii M, Nishimura H, Kusano KF, Qin G, Yoon YS, Wecker A, et al. Neuronal nitric oxide synthase mediates statin-induced restoration of vasa nervorum and reversal of diabetic neuropathy. Circulation. 2005;112:93–102
  321. Fried LF, Forrest KY, Ellis D, Chang Y, Silvers N, Orchard TJ. Lipid modulation in insulin-dependent diabetes mellitus: effect on microvascular outcomes. J Diabetes Complications. 2001;15:113–119
  322. Coste TC, Gerbi A, Vague P, Pieroni G, Raccah D. Neuroprotective effect of docosahexaenoic acid-enriched phospholipids in experimental diabetic neuropathy. Diabetes. 2003;52:2578–2585
  323. Gerbi A, Maixent J-M, Ansaldi J-L, Pierlovisi M, Coste T, Pelissier JF, et al. Fish oil supplementation prevents diabetes-induced nerve conduction velocity and neuroanatomical changes in rats. J Nutr. 1999;129:207–313
  324. Okuda Y, Mizutani M, Ogawa M, Sone H, Asano M, Asakura Y, et al. Long-term effects of eicosapentaenoic acid on peripheral diabetic neuropathy and serum lipids in patients with type II diabetes mellitus. J Diabetes Complications. 1996;10:280–287
  325. Burgess D, Hunt D, Li LP, Zhang J, Sy R, Laakso M, et al. Effects of fenofibrate on silent myocardial infarction, hospitalization for acute coronary syndromes and amputation in type 2 diabetes: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study [abstract]. Circulation. 2007;116:II_838
  326. Stevens MJ, Li F, Drel VR, Abatan OI, Kim H, Burnett D, et al. Nicotinamide reverses neurological and neurovascular deficits in streptozotocin diabetic rats. J Pharmacol Exp Ther. 2007;320:458–464
  327. Chew EY, Ambrosius WT, Howard LT, Greven CM, Johnson S, Danis RP, et al. Rationale, design and methods of the Action to Control Cardiovascular Risk in Diabetes Eye Study (ACCORD-EYE). Am J Cardiol. 2007;99(suppl):103i–111i
  328. Kim J, Ahn JH, Kim JH, Yu YS, Kim HS, Ha J, et al. Fenofibrate regulates retinal endothelial cell survival through the AMPK signal transduction pathway. Exp Eye Res. 2007;84:886–893
  329. Skrha J, Stulc T, Hilgertová J, Weiserová H, Kvasnicka J, Ceska R. Effect of simvastatin and fenofibrate on endothelium in Type 2 diabetes. Eur J Pharmacol. 2004;493:183–189
  330. Goetze S, Eilers F, Bungenstock A, Kintscher U, Stawowy P, Blaschke F, et al. PPAR activators inhibit endothelial cell migration by targeting Akt. Biochem Biophys Res Comm. 2002;293:1431–1437
  331. Demircan N, Safran BG, Soylu M, Ozcan AA, Sizmaz S. Determination of vitreous interleukin-1 (IL-1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy. Eye. 2006;20:1366–1369
  332. Ryan KE, McCance DR, Powell L, McMahon R, Trimble ER. Fenofibrate and pioglitazone improve endothelial function and reduce arterial stiffness in obese glucose tolerant men. Atherosclerosis. 2007;194:e123–e130
  333. Ducobu J, Scheen A, Van Gaal L, Velkeniers B, Hermans M. Belgian expert opinion: how to solve the residual risk in atherogenic dyslipidemic patients: place of fibrates. Acta Cardiol. 2008;63:235–248

 This work is funded by Solvay Pharmaceuticals, Inc.

 Statement of author disclosure: Please see the Author Disclosures section at the end of this article.

PII: S0002-9149(08)01750-5

doi: 10.1016/j.amjcard.2008.10.002

American Journal of Cardiology
Volume 102, Issue 10, Supplement , Pages 1K-34K , 17 November 2008