Advertisement

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

      Despite achieving targets for low-density lipoprotein (LDL) cholesterol, blood pressure, and glycemia in accordance with current standards of care, patients with dyslipidemia remain at high residual risk of vascular events. Atherogenic dyslipidemia, characterized by elevated triglycerides and low levels of high-density lipoprotein (HDL) cholesterol, often with elevated apolipoprotein B and non-HDL cholesterol, is common in patients with established cardiovascular disease (CVD), type 2 diabetes mellitus, or metabolic syndrome and contributes to both macrovascular and microvascular residual risk. However, atherogenic dyslipidemia is largely underdiagnosed and undertreated in clinical practice. The Residual Risk Reduction Initiative (R3i) was established to address this highly relevant clinical issue. The aims of this position paper are (1) to highlight evidence that atherogenic dyslipidemia is associated with residual macrovascular and microvascular risk in patients at high risk for CVD, despite current standards of care for dyslipidemia and diabetes; and (2) to recommend therapeutic intervention for reducing this residual vascular risk supported by evidence and expert consensus. Lifestyle modification with nutrition and exercise is an important, effective, and underutilized first step in reducing residual vascular risk. Therapeutic intervention aimed at achievement of all lipid targets is also often required. Combination lipid-modifying therapy, with the addition of niacin, a fibrate, or omega-3 fatty acids to statin therapy, increases the probability of achieving all lipid goals. Outcomes studies are in progress to evaluate whether these combination treatment strategies translate to a clinical benefit greater than that achieved with statins alone. The R3i highlights the need to address with lifestyle and/or pharmacotherapy the high level of residual risk of CVD events and microvascular complications among patients with dyslipidemia receiving therapy for high levels of LDL cholesterol and for diabetes in accordance with current standards of care.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Booth G.L.
        • Kapral M.K.
        • Fung K.
        • Tu J.V.
        Recent trends in cardiovascular complications among men and women with and without diabetes.
        Diabetes Care. 2006; 29: 32-37
        • 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
        • 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).
        Circulation. 2002; 106: 3143-3421
        • American Diabetes Association
        Standards of medical care in diabetes-2008.
        Diabetes Care. 2008; 31: S12-S54
        • Smith Jr, S.C.
        • Allen J.
        • Blair S.N.
        • Bonow R.O.
        • Brass L.W.
        • Fonarow G.C.
        • Grundy S.M.
        • Hiratzka L.
        • Jones D.
        • Krumholz H.M.
        • Mosca L.
        • Pasternak R.C.
        • Pearson T.
        • Pfeffer M.A.
        • Taubert K.A.
        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
        • Buse J.B.
        • Ginsberg H.N.
        • Bakris G.L.
        • Clark N.G.
        • Costa F.
        • Eckel R.
        • Fonseca V.
        • Gerstein H.C.
        • Grundy S.
        • Nesto R.W.
        • et al.
        • American Diabetes Association
        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
        • Graham I.
        • Atar D.
        • Borch-Johnsen K.
        • Boysen G.
        • Burell G.
        • Cifkova R.
        • Dallongeville J.
        • De Backer G.
        • Ebrahim S.
        • Gjelsvik B.
        • et al.
        • Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts)
        European guidelines on cardiovascular disease prevention in clinical practice: executive summary.
        Eur Heart J. 2007; 28: 2375-2414
        • Rydén L.
        • Standl E.
        • Bartnik M.
        • Van den Berghe G.
        • Betteridge J.
        • de Boer M.-J.
        • Cosentino F.
        • Jönsson B.
        • Laakso M.
        • Malmberg K.
        • et al.
        • Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD)
        Guidelines on diabetes, pre-diabetes, and cardiovascular disease: executive summary.
        Eur Heart J. 2007; 28: 88-136
        • Gregg E.W.
        • Gu Q.
        • Cheng Y.J.
        • Narayan K.M.
        • Cowie C.C.
        Mortality trends in men and women with diabetes, 1971–2000.
        Ann Intern Med. 2007; 147: 149-155
        • Lipscombe L.L.
        • Hux J.E.
        Trends in diabetes prevalence, incidence, and mortality in Ontario, Canada 1995–2005: a population-based study.
        Lancet. 2007; 369: 750-756
        • Zimmet P.
        • Alberti K.G.
        • Shaw J.
        Global and societal implications of the diabetes epidemic.
        Nature. 2001; 414: 782-787
        • 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
        • Ford E.S.
        • 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
        • Fox C.S.
        • Coady S.
        • Sorlie P.D.
        • D'Agostino Sr, R.B.
        • Pencina M.V.
        • Vasan R.S.
        • Meigs J.B.
        • Levy D.
        • Savage P.J.
        Increasing cardiovascular disease burden due to diabetes mellitus: the Framingham Heart Study.
        Circulation. 2007; 115: 1544-1550
        • Leibson C.L.
        • Williamson D.F.
        • Melton III, L.J.
        • Palumbo P.J.
        • Smith S.A.
        • Ransom J.E.
        • Schilling P.L.
        • Narayan K.M.
        Temporal trends in BMI among adults with diabetes.
        Diabetes Care. 2001; 24: 1584-1589
        • Murray C.J.
        • Lopez A.D.
        Regional patterns of disability-free life expectancy and disability-adjusted life expectancy: Global Burden of Disease Study.
        Lancet. 1997; 349: 1347-1352
        • Ho P.M.
        • Magid D.J.
        • Shetterly S.M.
        • Olson K.L.
        • Peterson P.N.
        • Masoudi F.A.
        • Rumfeld J.S.
        Importance of therapy intensification and medication nonadherence for blood pressure control in patients with coronary disease.
        Arch Intern Med. 2008; 168: 271-276
        • 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
      1. UKPDS report number 38.
        BMJ. 1998; 317: 703-713
        • Stratton I.M.
        • Cull C.A.
        • Adler A.I.
        • Matthews D.R.
        • Neil H.A.
        • Holman R.R.
        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
        • Kemp T.M.
        • Barr E.L.M.
        • Zimmet P.Z.
        • Cameron A.J.
        • Wellborn T.A.
        • Colagiuri S.
        • Phillips P.
        • Shaw J.E.
        Glucose, lipid, and blood pressure control in Australian adults with type 2 diabetes: the 1999–2000 AusDiab.
        Diabetes Care. 2005; 28: 1490-1492
        • Gaede P.
        • Vedel P.
        • Larsen N.
        • Jensen G.V.
        • Parving H.H.
        • Pedersen O.
        Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes.
        N Engl J Med. 2003; 348: 383-393
        • Gaede P.
        • Lund-Andersen H.
        • Parving H.H.
        • Pedersen O.
        Effect of a multifactorial intervention on mortality in type 2 diabetes.
        N Engl J Med. 2008; 358: 580-591
        • 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
        • Sacks F.M.
        • Pfeffer M.A.
        • Moye L.A.
        • Rouleau J.L.
        • Rutherford J.D.
        • Cole T.G.
        • Brown L.
        • Warnica J.W.
        • Arnold J.M.
        • Wun C.C.
        • Davis B.R.
        • Braunwald E.
        The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels.
        N Engl J Med. 1996; 335: 1001-1009
        • 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
        • 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
        • Shepherd J.
        • Blauw G.J.
        • Murphy M.B.
        • Bollen E.L.
        • Buckley B.M.
        • Cobbe S.M.
        • Ford I.
        • Gaw A.
        • Hyland M.
        • Jukema J.L.
        • et al.
        • PROSPER study group
        Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial.
        Lancet. 2002; 360: 1623-1630
        • Sever P.S.S.
        • Dahlöf B.
        • Poulter N.
        • Wedel H.
        • Beevers G.
        • Caufield M.
        • Collins R.
        • Kjeldsen S.E.
        • Kristinsson A.
        • McInnes G.T.
        • et al.
        • ASCOT Investigators
        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
        • 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
        • Knopp R.H.
        • D'Emden M.
        • Smilde J.G.
        • Pocock S.J.
        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
        • Shepherd J.
        • Cobbe S.M.
        • Ford I.
        • Isles C.G.
        • Lorimer A.R.
        • MacFarlane P.W.
        • McKillop J.H.
        • Packard C.J.
        Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia.
        N Engl J Med. 1995; 333: 1301-1307
        • Downs J.R.
        • Clearfield M.
        • Weis S.
        • Whitney E.
        • Shapiro D.R.
        • Beere P.A.
        • Langendorfer A.
        • Stein E.A.
        • Kruyer W.
        • Gotto Jr, A.M.
        • AFCAPS/TexCAPS Research Group
        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
        • Colhoun H.M.
        • Betteridge D.J.
        • Durrington P.N.
        • Hitman G.A.
        • Neil H.A.
        • Livingstone S.J.
        • Thomason M.J.
        • Mackness M.I.
        • Charlton-Menys V.
        • Fuller J.H.
        • CARDS Investigators
        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
        • Baigent C.
        • Keech A.
        • Kearney P.M.
        • Blackwell L.
        • Buck G.
        • Pollicino C.
        • Kirby A.
        • Sourjina T.
        • Peto R.
        • Collins R.
        • Simes R.
        • Cholesterol Treatment Trialists' (CTT) Collaborators
        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
        • Kearney P.M.
        • Blackwell P.M.
        • Collins R.
        • Keech A.
        • Simes J.
        • Peto R.
        • Armitage J.
        • Baigent C.
        • Cholesterol Treatment Trialists' (CTT) Collaborators
        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
        • Grundy S.M.
        • Cleeman J.I.
        • Merz C.N.
        • Brewer Jr, H.B.
        • Clark L.T.
        • Hunninghake D.B.
        • Pasternak R.C.
        • Smith Jr, S.C.
        • Stone N.J.
        • National Heart, Lung, and Blood Institute, American College of Cardiology Foundation, American Heart Association
        Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines.
        Circulation. 2004; 110 (Erratum in: Circulation 2004;110:763): 227-239
        • Brunzell J.D.
        • Davidson M.
        • Furberg C.D.
        • Goldberg R.B.
        • Howard B.V.
        • Stein J.H.
        • Witzum J.L.
        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
        • LaRosa J.C.
        • Grundy S.M.
        • Waters D.D.
        • Shear C.
        • Barter P.
        • Fruchart J.C.
        • Gotto A.M.
        • Greten H.
        • Kastelein J.J.
        • Shepherd J.
        • Wenger N.K.
        • Treating to New Targets (TNT) Investigators
        Intensive lipid lowering with atorvastatin in patients with stable coronary disease.
        N Engl J Med. 2005; 352: 1425-1435
        • Cannon C.P.
        • Braunwald E.
        • McCabe C.H.
        • Rader D.J.
        • Rouleau J.L.
        • Belder R.
        • Joyal S.V.
        • Hill K.A.
        • Pfeffer M.A.
        • Skene A.M.
        • Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction-22 Investigators
        Intensive versus moderate lipid lowering with statins after acute coronary syndromes.
        N Engl J Med. 2004; 350: 1495-1504
        • Centers for Disease Control and Prevention (CDC), National Diabetes-Surveillance System
        Diabetes data and trends.
        (CDC Web site) (Accessed June 2008)
        • International Diabetes Federation
        E-Atlas. 2005.
        (Accessed June 2008)
        • American Diabetes Association
        Economic consequences of diabetes mellitus in the U.S. in 1997: American Diabetes Association.
        Diabetes Care. 1998; 21: 296-309
        • American Diabetes Association
        Economic costs of diabetes in the U.S. in 2007.
        Diabetes Care. 2008; 31: 596-615
        • Yusuf S.
        • Hawken S.
        • Ounpuu S.
        • Dans T.
        • Avezum A.
        • Lanas F.
        • McQueen M.
        • Budaj A.
        • Pais P.
        • Varigos J.
        • Lisheng L.
        • INTERHEART Study Investigators
        Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
        Lancet. 2004; 364: 937-952
        • Austin M.A.
        • King M.C.
        • Vranizan K.M.
        • Krauss R.M.
        Atherogenic lipoprotein phenotype: a proposed genetic marker for coronary heart disease risk.
        Circulation. 1990; 82: 495-506
        • Ninomiya J.K.
        • L'Italien G.
        • Criqui M.H.
        • Whyte J.L.
        • Gamst A.
        • Chen R.S.
        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
        • Alsheikh-Ali A.A.
        • Lin J.-L.
        • Abourjaily P.
        • Ahearn D.
        • Kuvin J.T.
        • Karas J.H.
        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
        • 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
        • Austin M.A.
        • Hokanson J.E.
        • Edwards K.L.
        Hypertriglyceridemia as a cardiovascular risk factor.
        Am J Cardiol. 1998; 81: 7B-12B
        • Sarwar N.
        • Danesh J.
        • Eiriksdottir G.
        • Sigurdsson G.
        • Wareham N.
        • Bingham S.
        • Boekholdt S.M.
        • Khaw J.T.
        • Gnudson V.
        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
        • Nordestgaard B.G.
        • 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
        • Bansal S.
        • Buring J.E.
        • Rifai N.
        • Mora S.
        • Sacks F.M.
        • Ridker P.M.
        Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women.
        JAMA. 2007; 298: 309-316
        • 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
        • 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
        • St. Pierre A.C.
        • Cantin B.
        • Dagenais G.R.
        • Mauriege P.
        • Bernard P.M.
        • Despres J.P.
        • Lamarche B.
        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
        • Walldius G.
        • Jungner I.
        • Holme I.
        • Aastveit A.H.
        • 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
        • Shai I.
        • Rimm E.B.
        • Hankinson S.E.
        • Curhan G.
        • Manson J.E.
        • Rifai N.
        • Stampfer M.J.
        • Ma J.
        Multivariate assessment of lipid parameters as predictors of coronary heart disease among postmenopausal women: potential implications for clinical guidelines.
        Circulation. 2004; 110: 2824-2830
        • Jiang R.
        • Schulze M.B.
        • Li T.
        • Rifai N.
        • Stampfer M.J.
        • Rimm E.B.
        • Hu F.B.
        Non-HDL cholesterol and apolipoprotein B predict cardiovascular disease events among men with type 2 diabetes.
        Diabetes Care. 2004; 27: 1991-1997
        • Pischon T.
        • Girman C.J.
        • Sacks F.M.
        • Rifai N.
        • Stampfer M.J.
        • Rimm E.B.
        Non-high-density lipoprotein cholesterol and apolipoprotein B in the prediction of coronary heart disease in men.
        Circulation. 2005; 112: 3375-3383
        • Gotto Jr, A.M.
        • Whitney E.
        • Stein E.A.
        • Shapiro D.R.
        • Clearfield M.
        • Weis S.
        • Jou J.Y.
        • Langendorfer A.
        • Beere P.A.
        • Watson D.J.
        • Downs J.R.
        • de Cani J.S.
        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
        • Simes R.J.
        • Marschner I.C.
        • Hunt D.
        • Colquhoun D.
        • Sullivan D.
        • Stewart R.A.
        • Hague W.
        • Keech A.
        • Thompson P.
        • White H.
        • Shaw J.
        • Tonin A.
        • LIPID Investigators
        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
        • van Lennep J.E.
        • Westerveld H.T.
        • Van Lennep H.W.
        • Zwinderman A.H.
        • Erkelens D.W.
        • van der Wall E.E.
        Apolipoprotein concentrations during treatment and recurrent coronary artery disease events.
        Arterioscler Thromb Vasc Biol. 2000; 20: 2408-2413
        • Kathiresan S.
        • Otvos J.D.
        • Sullivan L.M.
        • Keyes M.J.
        • Schaefer E.J.
        • Wilson P.W.
        • D'Agostino R.B.
        • Vasan R.S.
        • Robins S.J.
        Increased small low-density lipoprotein particle number: a prominent feature of the metabolic syndrome in the Framingham Heart Study.
        Circulation. 2006; 113: 20-29
        • Vega G.L.
        • Grundy S.M.
        Occurrence of species of low-density lipoprotein with defective clearance in patients with primary moderate hypercholesterolaemia.
        J Intern Med. 1992; 232: 405-413
        • Alaupovic P.
        • Mack W.
        • Knight-Gibson C.
        • Hodis H.N.
        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
        • Sacks F.M.
        • Alaupovic P.
        • Moye L.A.
        • Cole T.G.
        • Sussex B.
        • Stampfer M.J.
        • Pfeffer M.A.
        • Braunwald E.
        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
        • Lee S.J.
        • Campos H.
        • Moye L.A.
        • Sacks F.M.
        LDL containing apolipoprotein CIII is an independent risk factor for coronary events in diabetic patients.
        Arterioscler Thromb Vasc Biol. 2003; 23: 853-858
        • Chivot L.
        • Mainard F.
        • Bigot E.
        • Bard J.M.
        • Auget J.L.
        • Madec Y.
        • Fruchart J.C.
        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
        • Luc G.
        • Fievet C.
        • Arveiler D.
        • Evans E.
        • Bard J.M.
        • Cambien F.
        • Fruchart J.C.
        • Ducimetiere P.
        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
        • Blankenhorn D.H.
        • Alaupovic P.
        • Wickham E.
        • Chin H.P.
        • Azen S.P.
        Prediction of angiographic change in native human coronary arteries and aortocoronary bypass grafts.
        Circulation. 1990; 81: 470-476
        • Hodis H.N.
        • Mack W.J.
        • Azen J.P.
        • Alaupovic P.
        • Pogoda J.M.
        • Labree L.
        • Hemphill L.C.
        • Kramsch D.M.
        • Blankenhorn D.H.
        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
        • Olivieri O.
        • Bassi A.
        • Stranieri C.
        • Trabetti E.
        • Martinelli N.
        • Pizzolo F.
        • Girelli D.
        • Friso S.
        • Pignatti P.F.
        • Corrocher R.
        Apolipoprotein C-III, metabolic syndrome, and risk of coronary artery disease.
        J Lipid Res. 2003; 44: 2374-2381
        • Onat A.
        • Hergenc G.
        • Sansoy V.
        • Fobker M.
        • Ceyhan K.
        • Toprak S.
        • Assmann G.
        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
        • Zheng C.Y.
        • Khoo C.
        • Ikewaki K.
        • Sacks F.M.
        Rapid turnover of apolipoprotein CIII containing triglyceride-rich lipoproteins contributing to formation of LDL subfractions.
        J Lipid Res. 2007; 48: 1190-1203
        • Chan D.C.
        • Watts G.F.
        • Nguyen M.N.
        • Barrett P.H.
        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
        • Kawakami A.
        • Aikawa M.
        • Libby P.
        • Alcaide P.
        • Luscinskas F.W.
        • Sacks F.M.
        Apolipoprotein CIII in apolipoprotein B lipoproteins enhances the adhesion of human monocytic cells to endothelial cells.
        Circulation. 2006; 113: 691-700
        • Kawakami A.
        • Aikawa M.
        • Alcaide P.
        • Luscinskas F.W.
        • Libby P.
        • Sacks F.M.
        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
        • Cohn J.S.
        • Patterson B.W.
        • Uffelman K.D.
        • 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
        • Campos H.
        • Perlov D.
        • Khoo C.
        • Sacks F.M.
        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
        • Juntti-Berggren L.
        • Refai E.
        • Appelskog I.
        • Andersson M.
        • Imreh G.
        • Dekki N.
        • Uhles S.
        • Yu L.
        • Griffiths W.J.
        • Zaitsev S.
        • 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
        • Chen M.
        • Breslow J.L.
        • 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
        • Klein R.L.
        • McHenry M.B.
        • Lok K.H.
        • Hunter S.J.
        • Le N.A.
        • Jenkins A.J.
        • Zheng D.
        • Semler A.
        • Page G.
        • Brown W.V.
        • Lyons T.J.
        • Garvey W.T.
        • DCCT/EDIC Research Group
        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
        • Birjmohun R.S.
        • Dallinga-Thie G.M.
        • Kuivenhoven J.A.
        • Stroes E.S.
        • Otvos J.D.
        • Wareham N.J.
        • Luben R.
        • Kastelein J.J.
        • Khaw K.T.
        • Boekholdt S.M.
        Apolipoprotein A-II is inversely associated with risk of future coronary artery disease.
        Circulation. 2007; 116: 2029-2035
        • Stampfer M.J.
        • Sacks F.M.
        • Salvini S.
        • Willett W.C.
        • Hennekens C.H.
        A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction.
        N Engl J Med. 1991; 325: 373-381
        • Ballantyne C.M.
        • Olsson A.G.
        • Cook T.J.
        • Mercuri M.F.
        • Pedersen T.R.
        • 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
        • Barter P.J.
        • Gotto A.M.
        • LaRosa J.C.
        • Maroni J.
        • Szarek M.
        • Grundy S.M.
        • Kastelein J.J.
        • Bittner V.
        • Fruchart J.C.
        • Treating to New Targets Investigators
        HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events.
        N Engl J Med. 2007; 357: 1301-1310
        • Miller M.
        • Cannon C.P.
        • Murphy S.A.
        • Qin J.
        • Ray K.K.
        • 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
        • Jenkins A.J.
        • Rowley K.G.
        • Lyons T.J.
        • Best J.D.
        • Hill M.A.
        • Klein R.L.
        Lipoproteins and diabetic microvascular complications.
        Curr Pharm Des. 2004; 10: 3395-3418
        • Chew E.Y.
        • Klein M.L.
        • Ferris III, F.L.
        • Remaley N.A.
        • Murphy R.P.
        • Chantry K.
        • Hoogwerf B.J.
        • Miller D.
        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
        • Ucgun N.I.
        • 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
        • Chowdhury T.A.
        • Hopkins D.
        • Dodson P.M.
        • Vafidis G.C.
        The role of serum lipids in exudative diabetic maculopathy: is there a place for lipid-lowering therapy?.
        Eye. 2002; 16: 689-693
        • Davis M.D.
        • Fisher M.R.
        • Gangnon R.E.
        • Barton F.
        • Aiello L.M.
        • Chew E.Y.
        • Ferris III, F.L.
        • Knatterud G.L.
        Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss.
        Invest Ophthalmol Vis Sci. 1998; 39: 233-252
        • Lyons T.J.
        • Jenkins A.J.
        • Zheng D.
        • Lackland D.T.
        • McGee D.
        • Garvey W.T.
        • Klein R.L.
        Diabetic retinopathy and serum lipoprotein subclasses in the DCCT/EDIC cohort.
        Invest Ophthalmol Vis Sci. 2004; 45: 910-918
        • Caramori M.L.
        • Fioretto P.
        • Mauer M.
        The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient?.
        Diabetes. 2000; 49: 1399-1408
        • Retnakaran R.
        • Cull C.A.
        • Thorne K.I.
        • Adler A.I.
        • Holman R.R.
        • UKPDS Study Group
        Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74.
        Diabetes. 2006; 55: 1832-1839
        • Hadjadj S.
        • Duly-Bouhanick B.
        • Bekherraz A.
        • Bridoux F.
        • Gallois Y.
        • Mauco G.
        • Ebran J.
        • Marre M.
        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
        • Cusick M.
        • Chew E.Y.
        • Hoogwerf B.
        • Agron E.
        • Wu L.
        • Lindley A.
        • Ferris III, F.L.
        • Early Treatment Diabetic Retinopathy Study Research Group
        Risk factors for renal replacement therapy in the Early Treatment Diabetic Retinopathy Study (ETDRS): ETDRS 26.
        Kidney Int. 2004; 66: 1173-1179
        • Smulders Y.
        • Rakic M.
        • Stehouwer C.
        • Weijers R.N.
        • Slaats E.H.
        • Silberbusch J.
        Determinants of progression of microalbuminuria in patients with NIDDM: a prospective study.
        Diabetes Care. 1997; 20: 999-1005
        • Chaturvedi N.
        • Fuller J.H.
        • Taskinen M.R.
        • 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
        • Jenkins A.J.
        • Lyons T.J.
        • Zheng D.
        • Otvos J.D.
        • Lackland D.T.
        • McGee D.
        • Garvey W.T.
        • Klein R.L.
        • DCCT/EDIC Research Group
        Lipoproteins in the DCCT/EDIC Research Group: associations with diabetic nephropathy.
        Kidney Int. 2003; 64: 817-828
        • Molitch M.E.
        • 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
        • Tesfaye S.
        • Chaturvedi N.
        • Eaton S.E.
        • Ward J.D.
        • Manes C.
        • Ionescu-Tirogoviste C.
        • Witte D.R.
        • Fuller J.H.
        • EURODIAB Prospective Complications Study Group
        Vascular risk factors and diabetic neuropathy.
        N Engl J Med. 2005; 352: 341-350
        • Kempler P.
        • Tesfaye S.
        • Chaturvedi N.
        • Stevens L.K.
        • Webb D.J.
        • Eaton S.
        • Kerenyi Z.
        • Tamas G.
        • Ward J.D.
        • EURODIAB IDDM Complications Study Group
        Autonomic neuropathy is associated with increased cardiovascular risk factors: the EURODIAB IDDM Complications Study.
        Diabet Med. 2002; 19: 900-909
        • 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
        • Delerive P.
        • Fruchart J.C.
        • Staels B.
        Peroxisome proliferator-activated receptors in inflammation control.
        J Endocrinol. 2001; 169: 453-459
        • Fruchart J.C.
        • 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
        • Dichtl W.
        • Nilsson L.
        • Goncalves I.
        • Ares M.P.
        • Banfi C.
        • Calara F.
        • Hamsten A.
        • Eriksson P.
        • Nilsson J.
        Very low-density lipoprotein activates nuclear factor-κB in endothelial cells.
        Circ Res. 1999; 84: 1085-1094
        • Kawakami A.
        • Aikawa M.
        • Nitta N.
        • Yoshida M.
        • Libby P.
        • Sacks F.M.
        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
        • Ting H.J.
        • Stice J.P.
        • Schaff U.Y.
        • Hui D.Y.
        • Rutledge J.C.
        • Knowlton A.A.
        • Passerini A.G.
        • Simon S.I.
        Triglyceride-rich lipoproteins prime aortic endothelium for inflammatory responses to TNF-α.
        Circ Res. 2007; 100: 381-390
        • Marx N.
        • Duez H.
        • Fruchart J.C.
        • Staels B.
        Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells.
        Circ Res. 2004; 94: 1168-1178
        • Pettersson C.
        • Fogelstrand L.
        • Rosengren B.
        • Stahlman S.
        • Hurt-Camejo E.
        • Fagerberg B.
        • Wiklund O.
        Increased lipolysis by secretory phospholipase A2 group V of lipoproteins in diabetic dyslipidaemia.
        J Intern Med. 2008; 264: 155-165
        • Kontush A.
        • Chapman M.J.
        Functionally defective high-density lipoprotein: a new therapeutic target at the crossroads of dyslipidaemia, inflammation, and atherosclerosis.
        Pharmacol Rev. 2006; 58: 342-374
        • De Souza J.A.
        • Vindis C.
        • Hansel B.
        • Negre-Salvayre A.
        • Therond P.
        • Cerrano Jr, C.V.
        • Chantepie S.
        • Salvayre S.
        • Bruckert E.
        • Chapman M.J.
        • Kontush A.
        Metabolic syndrome features small, apolipoprotein A-I-poor, triglyceride-rich HDL3 particles with defective anti-apoptotic activity.
        Atherosclerosis. 2008; 197: 84-94
        • Brown J.D.
        • Plutzky J.
        Peroxisome proliferator-activated receptors as transcriptional nodal points and therapeutic targets.
        Circulation. 2007; 115: 518-533
        • Mason R.P.
        Molecular basis of differences among statins and a comparison with antioxidant vitamin.
        Am J Cardiol. 2006; 98: 34P-41P
        • Ray K.K.
        • Cannon C.P.
        • 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: 18P-25P
        • Rosenson R.S.
        • Tangney C.C.
        Antiatherothrombotic properties of statins.
        JAMA. 1998; 279: 1643-1650
        • 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
        • 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
        • Giugliano D.
        • Esposito K.
        Mediterranean diet and metabolic diseases.
        Curr Opin Lipidol. 2008; 19: 63-68
        • McKellar G.
        • Morrison E.
        • McEntegart A.
        • Hampson R.
        • Tierney A.
        • Mackle G.
        • Scoular J.
        • Scott J.A.
        • Capell H.A.
        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
        • Gao X.
        • Chen H.
        • Fung T.T.
        • Logroscino G.
        • Schwarzschild M.A.
        • Hu F.B.
        • Ascherio A.
        Prospective study of dietary patterns and risk of Parkinson disease.
        Am J Clin Nutr. 2007; 86: 1486-1494
        • Scarmeas N.
        • Luchsinger J.A.
        • Mayeux R.
        • Stern Y.
        Mediterranean diet and Alzheimer disease mortality.
        Neurology. 2007; 69: 1084-1093
        • Trichopoulou A.
        • Kouris-Blazos A.
        • Wahlqvist M.L.
        • Gnardellis C.
        • Lagiou P.
        • Polychronopoulos E.
        • Vassilakou T.
        • Lipworth L.
        • Trichopoulos D.
        Diet and overall survival in the elderly.
        BMJ. 1995; 311: 1457-1460
        • Esposito K.
        • Marfella R.
        • Ciotola M.
        • Di Palo C.
        • Giugliano F.
        • D'Armiento M.
        • D'Andrea F.
        • Giugliano D.
        Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome.
        JAMA. 2004; 292: 1440-1446
        • Appel L.J.
        • Sacks F.M.
        • Carey V.J.
        • Obarzanek E.
        • Swain J.F.
        • Miller III, E.R.
        • Conlin P.R.
        • Erlinger T.P.
        • Laranjo N.M.
        • Charleston J.
        • McCarron P.
        • Bishop L.M.
        • OmniHeart Collaborative Research Group
        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
        • Sacks F.M.
        • Svetkey L.P.
        • Vollmer W.M.
        • Appel L.J.
        • Bray G.A.
        • Harsha D.
        • Obarzanek E.
        • Conlin P.R.
        • Miller III, E.R.
        • Simons-Morton D.G.
        • Karanja N.
        • Lin P.H.
        • DASH-Sodium Collaborative Research Group
        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
        • Schaefer E.J.
        • Gleason J.A.
        • Dansinger M.L.
        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
        • Brousseau M.E.
        • Schaefer E.J.
        Diet and coronary heart disease: clinical trials.
        Curr Atheroscler Rep. 2000; 2: 487-493
        • Parikh P.
        • McDaniel M.C.
        • Ashen M.D.
        • Miller J.I.
        • Sorrentino M.
        • Chan V.
        • Blumenthal R.S.
        • Sperling L.S.
        Diets and cardiovascular disease: an evidence-based assessment.
        J Am Coll Cardiol. 2005; 45: 1379-1387
        • De Lorgeril M.
        • Renaud S.
        • Mamelle N.
        • Salen P.
        • Martin J.L.
        • Monjaud I.
        • Guidollet J.
        • Touboul P.
        • Delaye J.
        Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease.
        Lancet. 1994; 343: 1454-1459
        • 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
        • Marchioli R.
        • Barzi F.
        • Bomba E.
        • Chieffo C.
        • Di Gregorio D.
        • Di Mascio R.
        • Franzosi M.G.
        • Geraci E.
        • Maggioni A.P.
        • Mantini L.
        • et al.
        • GISSI-Prevenzione Investigators
        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
        • Mensink R.P.
        • Zock P.L.
        • Kester A.D.
        • Katan M.B.
        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
        • Garg A.
        High-monounsaturated fat diet for diabetic patients: is it time to change the current dietary recommendations?.
        Diabetes Care. 1994; 17: 242-246
        • Covas M.I.
        • Nyyssonen K.
        • Poulsen H.E.
        • Kaikkonen J.
        • Zunft H.J.
        • Kiesewetter H.
        • Gaddi A.
        • de la Torre R.
        • Mursu J.
        • Baumler H.
        • et al.
        • EUROLIVE Study Group
        The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial.
        Ann Intern Med. 2006; 145: 333-341
        • Laaksonen D.E.
        • Nyyssönen K.
        • Niskanen L.
        • Rissanen T.H.
        • Salonen J.T.
        Prediction of cardiovascular mortality in middle-aged men by dietary and serum linoleic and polyunsaturated fatty acids.
        Arch Intern Med. 2005; 165: 193-199
        • Campos H.
        • Baylin A.
        • Willett W.C.
        Alpha linolenic acid and risk of nonfatal myocardial infarction.
        Circulation. 2008; 118: 339-344
        • Forsythe C.E.
        • Phinney S.D.
        • Fernandez M.L.
        • Quann E.E.
        • Wood R.J.
        • Bibus D.M.
        • Kraemer W.J.
        • Feinman R.D.
        • Volek J.S.
        Comparison of low fat and low carbohydrate diets on circulating fatty acid composition and markers of inflammation.
        Lipids. 2008; 43: 65-77
        • Bassuk S.S.
        • Manson J.E.
        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
        • Joen C.Y.
        • Lokken R.P.
        • Hu F.B.
        • Van Dam R.M.
        Physical activity of moderate intensity and risk of type 2 diabetes: a systematic review.
        Diabetes Care. 2007; 30: 744-752
        • 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
        • Weinstein A.R.
        • Sesso H.D.
        • Lee I.M.
        • Rexrode K.M.
        • Cook N.R.
        • Manson J.E.
        • Buring J.E.
        • Gaziano J.M.
        The joint effects of physical activity and body mass index on coronary heart disease risk in women.
        Arch Intern Med. 2008; 168: 884-890
        • DeFronzo R.A.
        • Sherwin R.S.
        • Kraemer N.
        Effect of physical training on insulin action in obesity.
        Diabetes. 1987; 36: 1379-1385
        • Thomas D.E.
        • Elliott E.J.
        • Naughton G.A.
        Exercise for type 2 diabetes mellitus.
        Cochrane Database System Rev. 2006; 3 (CD002968)
        • Sigal R.J.
        • Kenny G.P.
        • Boule N.G.
        • Wells G.A.
        • Prud'homme D.
        • Fortier M.
        • Reid R.D.
        • Tulloch H.
        • Coyle D.
        • Phillips P.
        • Jennings A.
        • Jaffey J.
        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
        • Kraus W.E.
        • Houmard J.A.
        • Duscha B.D.
        • Knetzger K.J.
        • Wharton M.B.
        • McCartney J.S.
        • Bales C.W.
        • Henes S.
        • Samsa G.P.
        • Otvos J.D.
        • Kulkarni K.R.
        • Slentz C.A.
        Effects of the amount and intensity of exercise on plasma lipoproteins.
        N Engl J Med. 2002; 347: 1483-1492
        • Kodama S.
        • Tanaka S.
        • Saito K.
        • Shu M.
        • Sone Y.
        • Onitake F.
        • Shimano H.
        • Yamamoto S.
        • Kondo K.
        • Ohashi Y.
        • Yamada N.
        • Sone H.
        Effect of aerobic exercise training on serum lipid levels of high density lipoprotein cholesterol: a meta-analysis.
        Arch Intern Med. 2007; 167: 999-1008
        • Kelley G.A.
        • Kelley K.S.
        • Tran Z.V.
        Exercise, lipids, and lipoproteins in older adults: a meta-analysis.
        Prev Cardiol. 2005; 8: 206-214
        • Kelley G.A.
        • Kelley K.S.
        Aerobic exercise and lipids and lipoproteins in children and adolescents: a meta-analysis of randomized controlled trials.
        Atherosclerosis. 2007; 191: 447-453
        • Kelley G.A.
        • Kelley K.S.
        • Tran Z.V.
        Walking, lipids, and lipoproteins: a meta-analysis of randomized controlled trials.
        Prev Med. 2004; 38: 651-661
        • Stewart K.J.
        • Bacher A.C.
        • Turner K.
        • Lim J.G.
        • Hees P.S.
        • Shapiro E.P.
        • Tayback M.
        • Ouyang P.
        Exercise and risk factors associated with metabolic syndrome in older adults.
        Am J Prev Med. 2005; 28: 9-18
        • Duncan G.E.
        • Anton S.D.
        • Sydeman S.J.
        • Newton Jr, R.L.
        • Corsica J.A.
        • Durning P.E.
        • Ketterson T.U.
        • Martin A.D.
        • Limacher M.C.
        • Perri M.G.
        Prescribing exercise at varied levels of intensity and frequency: a randomized trial.
        Arch Intern Med. 2005; 165: 2362-2369
        • Laaksonen D.E.
        • Lindstrom J.
        • Lakka T.A.
        • Eriksson J.G.
        • Niskanen L.
        • Wikstrom K.
        • Aunola S.
        • Keinanen-Kiuaanniemi S.
        • Laakso M.
        • Valle T.T.
        • et al.
        • Finnish Diabetes Prevention Study
        Physical activity in the prevention of type 2 diabetes: the Finnish diabetes prevention study.
        Diabetes. 2005; 54: 158-165
        • Johnson J.L.
        • Slenz C.A.
        • Houmard J.A.
        • Samsa G.P.
        • Duscha B.D.
        • Aiken L.B.
        • McCartney J.S.
        • Tanner C.J.
        • Kraus W.E.
        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
        • Chiuve S.E.
        • McCullough M.L.
        • Sacks F.M.
        • Rimm E.B.
        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
        • 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
        • 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
        • Staels B.
        • Fruchart J.C.
        Therapeutic roles of peroxisome proliferator-activated receptor agonists.
        Diabetes. 2005; 54: 2460-2470
        • Duez H.
        • Lefebvre B.
        • Poulain P.
        • Torra I.P.
        • Percevault F.
        • Luc G.
        • Peters J.M.
        • Gonzalez F.J.
        • Gineste R.
        • Helleboid S.
        • et al.
        Regulation of human apo A-I by gemfibrozil and fenofibrate through selective PPARα modulation.
        Arterioscler Thromb Vasc Biol. 2005; 25: 585-589
        • Chapman M.J.
        Fibrates in 2003: therapeutic action in atherogenic dyslipidaemia and future perspectives.
        Atherosclerosis. 2003; 171: 1-13
        • Feher M.D.
        • Caslake M.
        • Foxton J.
        • Cox A.
        • Packard C.J.
        Atherogenic lipoprotein phenotype in type 2 diabetes: reversal with micronised fenofibrate.
        Diabetes Metab Res Rev. 1999; 15: 395-399
        • Vakkilainen J.
        • Steiner G.
        • Ansquer J.C.
        • Aubin F.
        • Rattier S.
        • Foucher C.
        • Hamsten A.
        • Taskinen M.R.
        • DAIS Group
        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
        • Rosenson R.S.
        • Wolff D.A.
        • Huskin A.L.
        • Helenowski I.B.
        • Rademaker R.W.
        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
        • Ruotolo G.
        • Ericsson C.G.
        • Tettamanti C.
        • Karpe F.
        • Grip L.
        • Svane B.
        • Nilsson J.
        • de Faire U.
        • Hamsten A.
        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
        • Robins S.J.
        • Collins D.
        • Wittes J.T.
        • Papademetriou V.
        • Deedwania P.C.
        • Schaefer E.J.
        • McNamara J.R.
        • Kashyap M.L.
        • Hershman J.M.
        • Wexler L.F.
        • Rubins H.B.
        • VA-HIT Study Group
        Veterans Affairs High-Density Lipoprotein Intervention Trial.
        JAMA. 2001; 285: 1585-1591
        • Hiukka A.
        • Leinonen E.
        • Jauhiainen M.
        • Sundvall J.
        • Ehnholm C.
        • Keech A.C.
        • Taskinen M.R.
        Long-term effects of fenofibrate on VLDL and HDL subspecies in participants with type 2 diabetes.
        Diabetologia. 2007; 50: 2067-2075
        • May H.T.
        • Anderson J.L.
        • Pearson R.R.
        • Jensen J.R.
        • Horne B.D.
        • Lavasani F.
        • Yannicelli H.D.
        • Muhlestein J.B.
        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
        • Asztalos B.F.
        • Collins D.
        • Horvarth K.V.
        • Bloomfield H.E.
        • Robins S.J.
        • Schaefer E.J.
        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
        • Ooi T.C.
        • Cousins M.
        • Ooi D.S.
        • Nakajima K.
        • Edwards A.L.
        Effect of fibrates on postprandial remnant-like particles in patients with combined hyperlipidemia.
        Atherosclerosis. 2004; 172: 375-382
        • Rosenson R.S.
        • Huskin A.L.
        • Wolff D.A.
        • Helenowski I.B.
        • Rademaker A.W.
        Fenofibrate reduces fasting and postprandial inflammatory responses among hypertriglyceridemia patients with the metabolic syndrome.
        Atherosclerosis. 2008; 198: 381-388
        • Ooi T.C.
        • Heinonen T.
        • Alaupovic P.
        • Davignon J.
        • Leiter L.
        • Lupien P.J.
        • Sniderman A.D.
        • Tan M.H.
        • Tremblay G.
        • Sorisky A.
        • Shurzinske L.
        • Black D.M.
        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
        • Lamendola C.
        • Abbasi F.
        • Chu J.W.
        • Hutchinson H.
        • Cain V.
        • Leary E.
        • McLaughlin T.
        • Stein E.
        • Reaven G.
        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
        • Wagner J.A.
        • Larson P.J.
        • Weiss S.
        • Miller J.L.
        • Doebber T.W.
        • Wu M.S.
        • Moller D.E.
        • Gottesdiener K.M.
        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
        • Davidson M.H.
        • Bays H.E.
        • Stein E.
        • Maki K.C.
        • Shalwitz R.A.
        • Doyle R.
        Effects of fenofibrate on atherogenic dyslipidemia in hypertriglyceridemic subjects.
        Clin Cardiol. 2006; 29: 268-273
        • Sacks F.M.
        • Alaupovic P.
        • Moye L.A.
        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
        • Alaupovic P.
        • Heinonen T.
        • Shurzinske L.
        • Black D.M.
        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
        • Ballantyne C.M.
        • Herd J.A.
        • Ferlic L.L.
        • Dunn J.K.
        • Farmer J.A.
        • Jones P.H.
        • Schein J.R.
        • Gotto A.M.
        Influence of low HDL on progression of coronary artery disease and response to fluvastatin therapy.
        Circulation. 1999; 99: 736-743
        • Han S.H.
        • Quon M.J.
        • Koh K.K.
        Beneficial vascular and metabolic effects of peroxisome proliferatoractivated receptor-α activators.
        Hypertension. 2005; 46: 1086-1092
        • Zambon A.
        • Gervois P.
        • Pauletto P.
        • Fruchart J.C.
        • 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
        • Muhlestein J.B.
        • May H.T.
        • Jensen J.R.
        • Horne B.D.
        • Lanman R.B.
        • Lavasani F.
        • Wolfert R.L.
        • Pearson R.R.
        • Yannicelli H.D.
        • Anderson J.L.
        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
        • Koh K.
        • Quon M.J.
        • Han S.H.
        • Chung W.J.
        • Ahn J.Y.
        • Seo Y.H.
        • Choi I.S.
        • Shin E.K.
        Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia.
        J Am Coll Cardiol. 2005; 45: 1649-1653
        • Aguilar-Salinas C.A.
        • Lerman-Garber I.
        • Perez J.
        • Villa A.R.
        • Martinez C.L.
        • Turrubiatez L.C.
        • Wong B.
        • Gomez Perez F.J.
        • Gutierrez Robledo L.M.
        Ciprofibrate versus gemfibrozil in the treatment of mixed hyperlipidemias: an open-label, multicenter study.
        Metabolism. 2001; 50: 729-733
        • Lalloyer F.
        • Vandewalle B.
        • Percevault F.
        • Torpier G.
        • Kerr-Conte J.
        • Oosterveer M.
        • Paumelle R.
        • Fruchart J.C.
        • Kuipers F.
        • Pattou F.
        • Fievet C.
        • Staels B.
        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
        • 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
        • Orasanu G.
        • Ziouzenkova O.
        • Devchand P.R.
        • Nehra V.
        • Hamdy O.
        • Horton E.S.
        • Plutzky J.
        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
        • 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.
        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
        • Rubins H.B.
        • Robins S.J.
        • Collins D.
        • Nelson D.B.
        • Elam M.B.
        • Schaefer E.J.
        • Faas F.H.
        • Anderson J.W.
        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
        • 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
        • Tenenbaum A.
        • Motro M.
        • Fisman E.Z.
        • 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
        • Frick M.H.
        • Elo O.
        • Haapa K.
        • Heinonen O.P.
        • Heinsalmi P.
        • Helo P.
        • Huttunen J.K.
        • Kaitaniemi P.
        • Koskinen P.
        • Manninen V.
        Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia.
        N Engl J Med. 1987; 317: 1237-1245
        • Manninen V.
        • Tenkanen L.
        • Koskinen P.
        • Huttunen J.K.
        • Mantarri M.
        • Heinonen O.P.
        • Frick M.H.
        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
        • Keech A.
        • Simes R.J.
        • Barter P.
        • Best J.
        • Scott J.
        • Taskinen M.R.
        • Forder P.
        • Pillai A.
        • Davis T.
        • Glasziou P.
        • et al.
        • FIELD study investigators
        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
        • Scott R.
        • d'Emden M.
        • Best J.
        • Drury P.
        • Ehnholm C.
        • Kesaniemi A.
        • Pardy C.
        • Tse D.
        • Barter P.
        • Taskinen M.R.
        • Copt S.
        • Keech A.
        • FIELD Investigators
        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 (Abstract 3691): II_838
        • Robins S.J.
        • Rubins H.B.
        • Faas F.H.
        • Schaefer E.J.
        • Elam M.B.
        • Anderson J.W.
        • Collins D.
        • Veterans Affairs HDL Intervention Trial (VA-HIT)
        Insulin resistance and cardiovascular events with low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT).
        Diabetes Care. 2003; 26: 1513-1517
        • Otvos J.D.
        • Collins D.
        • Freedman D.S.
        • Shalaurova L.
        • Schaefer E.J.
        • McNamara J.R.
        • Bloomfield H.E.
        • Robins S.J.
        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
        • Tenkanen L.
        • Mantarri M.
        • Kovanen P.T.
        • 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
        • Keech A.
        • Simes J.
        • Barter P.
        • Best J.
        • Scott R.
        • Taskinen M.R.
        • FIELD Management Committee
        Correction to the FIELD study report [letter].
        Lancet. 2006; 368: 1415
        • Frick M.H.
        • Syvanne M.
        • Nieminen M.S.
        • Kauma H.
        • Majahalme S.
        • Virtanen V.
        • Kesaniemi Y.A.
        • Pasternack A.
        • Taskinen M.R.
        • Lopid Coronary Angiography Trial (LOCAT) Study Group
        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
        • Ericsson C.G.
        • 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
        • 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
        • Chinetti-Gbaguidi G.
        • Fruchart J.C.
        • Staels B.
        Pleiotropic effects of fibrates.
        Curr Atheroscler Rep. 2005; 7: 396-401
        • Dormandy J.A.
        • Charbonnel B.
        • Eckland D.J.
        • Erdmann E.
        • Massi-Benedetti M.
        • Moules I.K.
        • Skene A.M.
        • Lefebvre P.J.
        • Murray G.D.
        • Standl E.
        • et al.
        • PROactive Investigators
        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
        • Nissen S.E.
        • Nicholls S.J.
        • Wolski K.
        • Nesto R.
        • Kupfer S.
        • Perez A.
        • Jure H.
        • De Larochelliere R.
        • Staniloae C.S.
        • Mavromatis K.
        • et al.
        • PERISCOPE Investigators
        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
        • Keating G.M.
        • Croom K.F.
        Fenofibrate: a review of its use in primary dyslipidaemia, the metabolic syndrome and type 2 diabetes mellitus.
        Drugs. 2007; 67: 121-153
        • Grundy S.M.
        • Vega G.L.
        • Yuan Z.
        • Battisti W.P.
        • Brady W.E.
        • Palmisano J.
        Effectiveness and tolerability of simvastatin plus fenofibrate for combined hyperlipidemia (the SAFARI trial).
        Am J Cardiol. 2005; 95: 462-468
        • Athyros V.G.
        • Papageorgiou A.A.
        • Athyrou V.V.
        • Demitriadis D.S.
        • Kontopoulos A.G.
        Atorvastatin and micronized fenofibrate alone and in combination in type 2 diabetes with combined hyperlipidemia.
        Diabetes Care. 2002; 25: 1198-1202
        • Alsheikh-Ali A.A.
        • Kuvin J.T.
        • Karas R.H.
        Risk of adverse events with fibrates.
        Am J Cardiol. 2004; 94: 935-938
        • Ballantyne C.M.
        • Corsini A.
        • Davidson M.H.
        • Holdaas H.
        • Jacobson T.A.
        • Leitersdorf E.
        • Marz W.
        • Reckless J.P.
        • Stein E.A.
        Risk of myopathy with statin therapy in high-risk patients.
        Arch Intern Med. 2003; 163: 553-564
        • Rosenson R.S.
        Current overview of statin-induced myopathy.
        Am J Med. 2004; 116: 408-416
        • Jones P.H.
        • Davidson M.H.
        Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin.
        Am J Cardiol. 2005; 95: 120-122
        • Backman J.T.
        • Kyrklund C.
        • Kivisto K.T.
        • Wang J.S.
        • Neuvonen P.J.
        Plasma concentrations of active simvastatin acid are increased by gemfibrozil.
        Clin Pharmacol Ther. 2000; 68: 122-129
        • Kyrklund C.
        • Backman J.T.
        • Neuvonen M.
        • Neuvonen P.J.
        Gemfibrozil increases plasma pravastatin concentrations and reduces pravastatin renal clearance.
        Clin Pharmacol Ther. 2003; 73: 538-544
        • Kyrklund C.
        • Backman J.T.
        • Kivisto K.T.
        • Neuvonen M.
        • Laitila J.
        • Neuvonen P.J.
        Plasma concentrations of active lovastatin acid are markedly increased by gemfibrozil but not by bezafibrate.
        Clin Pharmacol Ther. 2001; 69: 340-345
        • Schneck D.W.
        • Birmingham B.K.
        • Zalikowski J.A.
        • Mitchell P.D.
        • Wang Y.
        • Martin P.D.
        • Lasseter K.C.
        • Brown C.D.
        • Windass A.S.
        • Raza A.
        The effect of gemfibrozil on the pharmacokinetics of rosuvastatin.
        Clin Pharmacol Ther. 2004; 75: 455-463
        • Backman J.T.
        • Luurila H.
        • Neuvonen M.
        • Neuvonen P.J.
        Rifampicin markedly decreases and gemfibrozil increases the plasma concentrations of atorvastatin and its metabolites.
        Clin Pharmacol Ther. 2005; 78: 154-167
        • Prueksaritanont T.
        • Subramanian R.
        • Fang X.
        • Ma B.
        • Qiu Y.
        • Lin J.H.
        • Pearson P.G.
        • Baillie T.A.
        Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization.
        Drug Metab Dispos. 2002; 30: 505-512
        • Prueksaritanont T.
        • Tang C.
        • Qiu Y.
        • Mu L.
        • Subramanian R.
        • Lin J.H.
        Effects of fibrates on metabolism of statins in human hepatocytes.
        Drug Metab Dispos. 2002; 30: 1280-1287
        • Pan W.
        • Gustavsson L.E.
        • Achari R.
        • Rieser M.J.
        • Ye X.
        • Gutterman C.
        • Wallin B.A.
        Lack of clinically significant pharmacokinetic interaction between fenofibrate and pravastatin in healthy volunteers.
        J Clin Pharmacol. 2000; 40: 316-323
        • Bergman A.J.
        • Murphy G.
        • Burke J.
        • Zhao J.J.
        • Valesky R.
        • Liu L.
        • Lasseter K.C.
        • He W.
        • Prueksaritanont T.
        • Qiu Y.
        • et al.
        Simvastatin does not have a clinically significant pharmacokinetic interaction with fenofibrate in humans.
        J Clin Pharmacol. 2004; 44: 1054-1062
        • Gustavson L.E.
        • Schweitzer S.M.
        • Koehne-Voss S.
        • Achari R.
        • Chira T.O.
        • Esslinger H.U.
        • Yannicelli H.D.
        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
        • Martin P.D.
        • Dane A.L.
        • Schneck D.W.
        • Warwick M.J.
        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
        • Penn R.
        • Williams III, R.X.
        • Guha-Ray D.K.
        • Sawyers W.G.
        • Braun S.L.
        • Rains K.T.
        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
        • Davidson M.H.
        • Armani A.
        • McKenney J.M.
        • Jacobson T.A.
        Safety considerations with fibrate therapy.
        Am J Cardiol. 2007; 99: 3C-18C
        • Tonelli M.
        • Collins D.
        • Robins S.
        • Bloomfield H.
        • Curhan G.C.
        • 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
        • 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
        • Ford E.S.
        • Smith S.J.
        • Stroup K.K.
        • Steinberg K.K.
        • Mueller P.W.
        • Thacker S.B.
        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
        • Spence J.D.
        • Ban H.
        • Chambless L.E.
        • Stampfer M.J.
        Vitamin Intervention for Stroke Prevention trial: an efficacy analysis.
        Stroke. 2005; 36: 2404-2409
        • Bonaa K.H.
        • Njolstad I.
        • Ueland P.M.
        • Schirmer H.
        • Tverdal A.
        • Steigen T.
        • Wang H.
        • Nordrehaug J.E.
        • Arnesen E.
        • Rasmussen K.
        • NORVIT Trial Investigators
        Homocysteine lowering and cardiovascular events after acute myocardial infarction.
        N Engl J Med. 2006; 354: 1578-1588
        • 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
        • Ginsberg H.N.
        • Bonds D.
        • Lovato L.C.
        • Crouse J.R.
        • Elam M.B.
        • Linz P.E.
        • O'Connor P.J.
        • Leiter L.A.
        • Weiss D.
        • Lipkin E.
        • Fleg F.L.
        • ACCORD Study Group
        Evolution of the lipid trial protocol of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.
        Am J Cardiol. 1997; 99: 56i-67i
        • Morgan J.M.
        • Capuzzi D.M.
        • Guyton J.R.
        • Centor R.M.
        • Goldberg R.
        • Robbins D.C.
        • DiPette D.C.
        • Jenkins S.
        • Marcovina S.
        Treatment effect of NIASPAN, a controlled-release niacin, in patients with hypercholesterolemia: a placebo-controlled trial.
        J Cardiovasc Pharmacol Ther. 1996; 1: 195-202
        • Goldberg A.
        • Alagona Jr, P.
        • Capuzzi D.M.
        • Guyton J.
        • Morgan J.M.
        • Rodgers J.
        • Sachson R.
        • Samuel P.
        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
        • McCormack P.L.
        • Keating G.M.
        Prolonged-release nicotinic acid: a review of its use in the treatment of dyslipidaemia.
        Drugs. 2005; 65: 2719-2740
        • Morgan J.M.
        • Capuzzi D.M.
        • Baksh R.I.
        • Intenzo C.
        • Carey C.M.
        • Reese D.
        • Walker K.
        Effects of extended-release niacin on lipoprotein subclass distribution.
        Am J Cardiol. 2003; 91: 1432-1436
        • Pan J.
        • Lin M.
        • Kesala R.L.
        • Van J.
        • Charles M.A.
        Niacin treatment of the atherogenic lipid profile and Lp(a) in diabetes.
        Diabetes Obes Metab. 2002; 4: 255-261
        • Karpe F.
        • Frayn K.N.
        The nicotinic acid receptor – a new mechanism for an old drug.
        Lancet. 2004; 363: 1892-1894
        • Soudijn W.
        • van Wijngaarden I.
        • Ijzerman A.P.
        Nicotinic acid receptor subtypes and their ligands.
        Med Res Rev. 2007; 27: 417-433
        • Wang W.
        • Basinger A.
        • Neese R.A.
        • Shane B.
        • Myong S.A.
        • Christiansen M.
        • Hellerstein M.K.
        Effect of nicotinic acid administration on hepatic very low density lipoprotein-triglyceride production.
        Am J Physiol Endocrinol Metab. 2001; 280: E540-E547
        • Kamanna V.S.
        • Kashyap M.L.
        Mechanism of action of niacin on lipoprotein metabolism.
        Curr Atheroscler Rep. 2000; 2: 36-46
        • Shepherd J.
        • Packard C.J.
        • Patsch J.R.
        • Gotto Jr, A.M.
        • Taunton O.D.
        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
        • Hernandez M.
        • Wright S.D.
        • Cai T.Q.
        Critical role of cholesterol ester transfer protein in nicotinic acid-mediated HDL elevation in mice.
        Biochem Biophys Res Commun. 2007; 355: 1075-1080
        • Rosenson R.S.
        Antiatherothrombotic effects of nicotinic acid.
        Atherosclerosis. 2003; 171: 87-96
        • Coronary Drug Project Research Group
        Clofibrate and niacin in coronary heart disease.
        JAMA. 1975; 231: 360-381
        • Canner P.L.
        • Berge K.G.
        • Wenger N.K.
        • Stamler J.
        • Friedman L.
        • Prineas R.J.
        • Friedewald W.
        Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin.
        J Am Coll Cardiol. 1986; 8: 1245-1255
        • Canner P.L.
        • Furberg C.D.
        • Terrin M.L.
        • McGovern M.E.
        Benefits of niacin by glycemic status in patients with healed myocardial infarction (from the Coronary Drug Project).
        Am J Cardiol. 2005; 95: 254-257
        • Brown G.
        • Albers J.J.
        • Fisher L.D.
        • Schaefer S.M.
        • Lin J.T.
        • Kaplan C.
        • Zhao X.Q.
        • Bisson B.D.
        • Fitzpatrick V.F.
        • Dodge H.T.
        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
        • McKenney J.M.
        • Jones P.H.
        • Bays H.E.
        • Knopp R.H.
        • Kashyap M.L.
        • Ruoff G.E.
        • McGovern M.E.
        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
        • Brown B.G.
        • Zhao X.Q.
        • Chait A.
        • Fisher L.D.
        • Cheung M.C.
        • Morse J.S.
        • Dowdy A.A.
        • Marino E.K.
        • Bolson E.L.
        • Alaupovic P.
        • Frohlich J.
        • Albers J.J.
        Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease.
        N Engl J Med. 2001; 345: 1583-1592
        • Taylor A.J.
        • Sullenberger L.E.
        • Lee H.J.
        • Lee J.K.
        • Grace K.A.
        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
        • Taylor A.J.
        • Lee H.J.
        • Sullenberger L.E.
        The effect of 24-months of combination statin and extended-release niacin on carotid intima-media thickness.
        Curr Med Res Opin. 2006; 22: 2243-2250
        • 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
        • Brown G.
        Expert commentary: niacin safety.
        Am J Cardiol. 2007; 99: 32C-34C
        • Guyton J.R.
        • Bays H.E.
        Safety considerations with niacin therapy.
        Am J Cardiol. 2007; 99: 22C-31C
        • Lai E.
        • De Lepeleire I.
        • Crumley T.M.
        • Liu F.
        • Wenning L.A.
        • Michiels N.
        • Vets E.
        • O'Neill G.
        • Wagner J.A.
        • Gottesdiener K.
        Suppression of niacin-induced vasodilation with an antagonist to prostaglandin D2 receptor subtype1.
        Clin Pharmacol Ther. 2007; 81: 849-857
        • 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 (Abstract P715): 108
        • Paolini J.F.
        • Mitchel Y.B.
        • Reyes R.
        • Kher U.
        • Lai E.
        • Watson D.J.
        • Norquist J.M.
        • Meehan A.G.
        • Bays H.E.
        • Davidson M.
        • Ballantyne C.M.
        Effects of laropiprant on nicotinic acid-induced flushing in patients with dyslipidemia.
        Am J Cardiol. 2008; 101: 625-630
        • Grundy S.M.
        • Vega G.L.
        • McGovern M.E.
        • Tulloch B.P.
        • Kendall D.M.
        • Fitz-Patrick D.
        • Ganda O.P.
        • Rosenson R.S.
        • Buse J.B.
        • Robertson D.D.
        • Sheehan J.P.
        • Diabetes Multicenter Research Group
        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
        • Ginsberg H.N.
        Niacin in the metabolic syndrome: more risk than benefit?.
        Nature Clin Pract Endo Metab. 2006; 2: 2-3
        • Clinical Trial
        AIM HIGH: Niacin plus statin to prevent vascular events.
        (Accessed June 5, 2008)
      2. Clinical Trial Treatment of HDL to reduce the incidence of vascular events.
        (Accessed 5 June 2008)
        • Harris W.S.
        • Connor W.E.
        • Alam N.
        • Illingworth D.R.
        Reduction of postprandial triglyceridemia in humans by dietary n-3 fatty acids.
        J Lipid Res. 1988; 29: 1451-1460
        • Harris W.S.
        Omega-3 fatty acids and cardiovascular disease: a case for omega-3 index as a new risk factor.
        Pharmacol Res. 2007; 55: 217-223
        • Montori V.M.
        • Farmer A.
        • Wollan P.C.
        • Dinheen S.F.
        Fish oil supplementation in type 2 diabetes: a quantitative systemic review.
        Diabetes Care. 2000; 23: 1407-1415
        • Morris M.C.
        • Sacks F.
        • Rosner B.
        Does fish oil lower blood pressure?.
        Circulation. 1993; 88: 523-533
        • Appel L.J.
        • Miller III, E.R.
        • Seidler A.J.
        • Whelton P.K.
        Does supplementation of diet with ‘fish oil’ reduce blood pressure?.
        Arch Intern Med. 1993; 153: 1429-1438
        • Kris-Etherton P.M.
        • Harris W.S.
        • Appel L.J.
        • American Heart Association, Nutrition Committee
        Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease.
        Circulation. 2002; 106: 2742-2757
        • Sethi S.
        • Ziouzenkova O.
        • Ni H.
        • Wagner D.D.
        • Plutzky J.
        • Mayadas T.N.
        Oxidized omega-3 fatty acids in fish oil inhibit leukocyte-endothelial interactions through activation of PPAR α.
        Blood. 2002; 100: 1340-1346
      3. Secondary prevention in primary and secondary care for patients following a myocardial infarction.
        (Accessed October 22, 2008)
        • Harris W.S.
        • Ginsberg H.N.
        • Arunakul N.
        • Schachter N.S.
        • Windsor S.L.
        • Adams M.
        • Berglund O.
        • Osmundsen K.
        Safety and efficacy of Omacor in severe hypertriglyceridemia.
        J Cardiovasc Risk. 1997; 4: 385-391
        • Davidson M.H.
        • Stein E.A.
        • Bays H.E.
        • Maki K.C.
        • Doyle R.T.
        • Shalwitz R.A.
        • Ballantyne C.M.
        • Ginsberg H.N.
        • COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators
        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
        • Durrington P.N.
        • Bhatnagar D.
        • Mackness M.I.
        • Morgan J.
        • Julier K.
        • Khan M.A.
        • France M.
        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
        • Leaf A.
        • Kang J.X.
        • Xiao Y.F.
        Omega-3 fatty acids and ventricular arrhythmias.
        World Rev Nutr Diet. 2005; 94: 129-138
        • Leaf A.
        Omega-3 fatty acids and prevention of arrhythmias.
        Curr Opin Lipidol. 2007; 18: 31-34
        • Yokoyama M.
        • Origasa H.
        • Matsuzaki M.
        • Matsuzawa Y.
        • Saito Y.
        • Ishikawa Y.
        • Oikawa S.
        • Sasaki K.
        • Hishida H.
        • Itakura H.
        • et al.
        • Japan EPA Lipid Intervention Study (JELIS) Investigators
        Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomized open-label, blinded endpoint analysis.
        Lancet. 2007; 369: 1090-1098
        • 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)
        • Morehouse L.A.
        • Sugarman E.D.
        • Bourassa P.A.
        • Sand T.M.
        • Zimetti F.
        • Gao F.
        • Rothblat G.H.
        • Milici A.J.
        Inhibition of CETP activity by torcetrapib reduces susceptibility to diet-induced atherosclerosis in New Zealand White rabbits.
        J Lipid Res. 2007; 48: 1263-1272
        • Osono Y.
        • Woollett L.A.
        • Marotti K.R.
        • Melchior G.W.
        • Dietschy J.M.
        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
        • Boekholdt S.M.
        • Sacks F.M.
        • Jukema J.W.
        • Shepherd J.
        • Freeman D.J.
        • McMahon A.D.
        • Cambien F.
        • Nicaud V.
        • de Grooth G.J.
        • Talmud P.J.
        • 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
        • Nagano M.
        • Yamashita S.
        • Hirano K.
        • Takano M.
        • Maruyama T.
        • Ishihara M.
        • Sagehashi Y.
        • Kujiraoka T.
        • Tanaka K.
        • Hattori H.
        • et al.
        Molecular mechanisms of cholesteryl ester transfer protein deficiency in Japanese.
        J Atheroscler Thromb. 2004; 11: 110-121
        • Barzilai N.
        • Atzmon G.
        • Schechter E.J.
        • Schaefer E.J.
        • Cupples A.L.
        • Lipton R.
        • Cheng S.
        • Shuldiner A.R.
        Unique lipoprotein phenotype and genotype associated with exceptional longevity.
        JAMA. 2003; 290: 2030-2040
        • Curb J.D.
        • Abbott R.D.
        • Rodriguez B.L.
        • Masaki K.
        • Chen R.
        • Sharp D.S.
        • Tall A.R.
        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
        • Brousseau M.E.
        • O'Connor Jr, J.J.
        • Ordovas J.M.
        • Collins D.
        • Otvos J.D.
        • Massov T.
        • McNamara J.R.
        • Rubins H.B.
        • Robins S.J.
        • Schaefer E.J.
        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
        • Barter P.
        • Caulfield M.
        • Eriksson M.
        • Grundy S.M.
        • Kastelein J.J.
        • Komadja M.
        • Lopez-Sendon J.
        • Mosca L.
        • Tardif J.C.
        • Waters D.D.
        • ILLUMINATE Investigators
        Effects of torcetrapib on morbidity and mortality in patients at high risk for coronary events.
        N Engl J Med. 2007; 357: 2109-2122
        • Nissen S.E.
        • Tardif J.C.
        • Nicholls S.J.
        • Revkin J.H.
        • Shear C.L.
        • Duggan W.T.
        • Ruzyllo W.
        • Bachinsky W.B.
        • Lasala G.P.
        • Tuzcu E.M.
        • ILLUSTRATE Investigators
        Effect of torcetrapib on the progression of coronary atherosclerosis.
        N Engl J Med. 2007; 356: 1304-1316
        • Kastelein J.J.P.
        • van Leuven S.I.
        • Burgess L.
        • Evans G.W.
        • Kuivenhoven J.A.
        • Barter P.J.
        • Revkin J.H.
        • Grobbee D.E.
        • Riley W.A.
        • Shear C.L.
        • Duggan W.T.
        • Bots M.L.
        • RADIANCE Investigators
        Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia.
        N Engl J Med. 2007; 356: 1620-1630
        • Bots M.L.
        • Visseren F.L.
        • Evans G.W.
        • Riley W.A.
        • Revkin J.H.
        • Tegeler C.H.
        • Shear C.L.
        • Duggan W.T.
        • Vicari R.M.
        • Grobbee D.E.
        • Kastelein J.J.
        • RADIANCE 2 Investigators
        Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial.
        Lancet. 2007; 370: 153-160
        • Krishna R.
        • Anderson M.S.
        • Bergman A.J.
        • Jin B.
        • Fallon M.
        • Cote J.
        • Rosko K.
        • Chavez-Eng C.
        • Lutz R.
        • Bloomfield D.M.
        • 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
        • Hollander P.
        Endocannabinoid blockade for improving glycemic control and lipids in patients with type 2 diabetes mellitus.
        Am J Med. 2007; 120: S18-S28
        • Scheen A.J.
        • Finer N.
        • Hollander P.
        • Jensen M.D.
        • Van Gaal L.F.
        • 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
        • Despres J.P.
        • 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
        • Henness S.
        • Robinson D.M.
        • Lyseng-Williamson K.A.
        Rimonabant.
        Drugs. 2006; 66: 2109-2119
        • Van Gaal L.F.
        • Scheen A.J.
        • Rissanen A.M.
        • 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
        • Van Gaal L.
        • Pi-Sunyer X.
        • Despres J.P.
        • 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: S229-S2240
        • Nissen S.E.
        • Nicholls S.J.
        • Wolski K.
        • Rodes-Cabau J.
        • Cannon C.P.
        • Deanfield J.E.
        • Despres J.P.
        • Kastelein J.J.
        • Steinhubl S.R.
        • Kapadia S.
        • et al.
        • STRADIVARIUS Investigators
        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
        • Christensen R.
        • Kristensen P.K.
        • Bartels E.M.
        • Bliddal H.
        • Astrup A.
        Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials.
        Lancet. 2007; 370: 1706-1713
        • Bell R.A.
        • Camacho F.
        • Duren-Winfield V.T.
        • Bonds D.E.
        • Anderson R.T.
        • Konen J.C.
        • Goff Jr, D.C.
        Improving diabetes care among low-income North Carolinians: Project IDEAL.
        N C Med J. 2005; 66: 96-102
        • Nathan D.M.
        • Buse J.B.
        • Davidson M.B.
        • Heine R.J.
        • Holman R.R.
        • Sherwin R.
        • Zinman B.
        • Professional Practice Committee, American Diabetes Association, European Association for the Study of Diabetes
        Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy.
        Diabetologia. 2006; 49: 1711-1721
        • American Diabetes Association
        Nutrition recommendations and interventions for diabetes – 2006: a position statement of the American Diabetes Association.
        Diabetes Care. 2006; 29: 2140-2155
        • 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
        • Patel A.
        • MacMahon S.
        • Chalmers J.
        • Neal B.
        • Woodward M.
        • Billot L.
        • Harrap S.
        • Poulter N.
        • Marre M.
        • Cooper M.
        • et al.
        • ADVANCE Collaborative Group
        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
        • 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
        • Sandhu S.
        • Wiebe N.
        • Fried L.F.
        • Tonelli M.
        Statins for improving renal outcomes: a meta-analysis.
        J Am Soc Nephrol. 2006; 17: 2006-2016
        • Douglas K.
        • O'Malley P.G.
        • Jackson J.L.
        Meta-analysis: the effect of statins on albuminuria.
        Ann Intern Med. 2006; 145: 117-124
        • 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
        • Athyros V.G.
        • Mikhailidis D.P.
        • Papageorgiou A.A.
        • Symeonidis A.N.
        • Pehlivanidis A.N.
        • Bouloukos V.I.
        • Elisaf M.
        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
        • Tonelli M.
        • Isles C.
        • Craven T.
        • Tonkin A.
        • Pfeffer M.A.
        • Shepherd J.
        • Sacks F.M.
        • Furberg C.
        • Cobbe S.M.
        • Simes 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
        • Shepherd J.
        • Kastelein J.J.
        • Bittner V.
        • Deedwania P.
        • Breazna A.
        • Dobson S.
        • Wilson D.J.
        • Zuckerman A.
        • Wenger N.K.
        • Treating to New Targets Investigators
        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
        • Campese V.M.
        • Park J.
        HMG-CoA reductase inhibitors and the kidney.
        Kidney Int. 2007; 71: 1215-1222
        • Ansquer J.C.
        • Foucher C.
        • Rattier S.
        • Taskinen M.R.
        • 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
        • Dodson P.M.
        Medical treatment for diabetic retinopathy: do the FIELD microvascular study results support a role for lipid lowering?.
        Practical Diabetes International. 2008; 25: 76-79
        • Zhang J.
        • McGwin Jr, G.
        Association of statin use with the risk of developing diabetic retinopathy.
        Arch Ophthalmol. 2007; 125: 1096-1099
        • 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
        • 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.
        • et al.
        • FIELD Study Investigators
        Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial.
        Lancet. 2007; 370: 1687-1697
        • Simó R.
        • Hernández C.
        Fenofibrate for diabetic retinopathy.
        Lancet. 2007; 370: 1667-1668
        • 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: S35-S39
        • 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
        • Davis T.M.
        • Yeap B.B.
        • Davis W.A.
        • Bruce D.G.
        Lipid-lowering therapy and peripheral sensory neuropathy in type 2 diabetes: the Fremantle Diabetes Study.
        Diabetologia. 2008; 51: 562-566
        • Ii M.
        • Nishimura H.
        • Kusano K.F.
        • Qin G.
        • Yoon Y.S.
        • Wecker A.
        • Asahara T.
        • Losordo D.W.
        Neuronal nitric oxide synthase mediates statin-induced restoration of vasa nervorum and reversal of diabetic neuropathy.
        Circulation. 2005; 112: 93-102
        • Fried L.F.
        • Forrest K.Y.
        • Ellis D.
        • Chang Y.
        • Silvers N.
        • Orchard T.J.
        Lipid modulation in insulin-dependent diabetes mellitus: effect on microvascular outcomes.
        J Diabetes Complications. 2001; 15: 113-119
        • Coste T.C.
        • Gerbi A.
        • Vague P.
        • Pieroni G.
        • Raccah D.
        Neuroprotective effect of docosahexaenoic acid-enriched phospholipids in experimental diabetic neuropathy.
        Diabetes. 2003; 52: 2578-2585
        • Gerbi A.
        • Maixent J.-M.
        • Ansaldi J.-L.
        • Pierlovisi M.
        • Coste T.
        • Pelissier J.F.
        • Vague P.
        • Raccah D.
        Fish oil supplementation prevents diabetes-induced nerve conduction velocity and neuroanatomical changes in rats.
        J Nutr. 1999; 129: 207-313
        • Okuda Y.
        • Mizutani M.
        • Ogawa M.
        • Sone H.
        • Asano M.
        • Asakura Y.
        • Isaka M.
        • Suzuki M.
        • Kawakami Y.
        • Field J.B.
        • Yamashita K.
        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
        • Burgess D.
        • Hunt D.
        • Li L.P.
        • Zhang J.
        • Sy R.
        • Laakso M.
        • Davis T.
        • Colman P.
        • Forder P.
        • Williamson E.
        • Pike R.
        • Keech A.
        • FIELD Investigators
        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
        • Stevens M.J.
        • Li F.
        • Drel V.R.
        • Abatan O.I.
        • Kim H.
        • Burnett D.
        • Larkin D.
        • Obrosova I.G.
        Nicotinamide reverses neurological and neurovascular deficits in streptozotocin diabetic rats.
        J Pharmacol Exp Ther. 2007; 320: 458-464
        • Chew E.Y.
        • Ambrosius W.T.
        • Howard L.T.
        • Greven C.M.
        • Johnson S.
        • Danis R.P.
        • Davis M.D.
        • Genuth S.
        • Domanski M.
        • ACCORD Study Group
        Rationale, design and methods of the Action to Control Cardiovascular Risk in Diabetes Eye Study (ACCORD-EYE).
        Am J Cardiol. 2007; 99: 103i-111i
        • Kim J.
        • Ahn J.H.
        • Kim J.H.
        • Yu Y.S.
        • Kim H.S.
        • Ha J.
        • Shinn S.H.
        • Oh Y.S.
        Fenofibrate regulates retinal endothelial cell survival through the AMPK signal transduction pathway.
        Exp Eye Res. 2007; 84: 886-893
        • 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
        • Goetze S.
        • Eilers F.
        • Bungenstock A.
        • Kintscher U.
        • Stawowy P.
        • Blaschke F.
        • Graf K.
        • Law R.E.
        • Fleck E.
        • Grafe M.
        PPAR activators inhibit endothelial cell migration by targeting Akt.
        Biochem Biophys Res Comm. 2002; 293: 1431-1437
        • Demircan N.
        • Safran B.G.
        • Soylu M.
        • Ozcan A.A.
        • Sizmaz S.
        Determination of vitreous interleukin-1 (IL-1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy.
        Eye. 2006; 20: 1366-1369
        • Ryan K.E.
        • McCance D.R.
        • Powell L.
        • McMahon R.
        • Trimble E.R.
        Fenofibrate and pioglitazone improve endothelial function and reduce arterial stiffness in obese glucose tolerant men.
        Atherosclerosis. 2007; 194: e123-e130
        • 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