Current Cardiology Reports

, Volume 14, Issue 6, pp 721–731

Management of Dyslipidemias in the Presence of the Metabolic Syndrome or Type 2 Diabetes

Lipid Abnormalities and Cardiovascular Prevention (G De Backer, Section Editor)


In the metabolic syndrome and type 2 diabetes, excess energy intake on the background of genetic predisposition and lifestyle factors leads to the dysregulation of fatty acid metabolism and acquired insulin resistance. These initial metabolic defects are reflected to both lipoprotein and glucose metabolism and contribute to increased risk for cardiovascular disease. However, even after controlling for the traditional cardiovascular risk factors, subjects with the metabolic syndrome and type 2 diabetes remain at high residual cardiovascular risk despite of low/normal LDL-cholesterol concentration. For 2 decades, statin therapy has been the cornerstone of treatment of dyslipidemia in these disorders. In the metabolic syndrome and type 2 diabetes, only statin treatment has demonstrated consistently a significant reduction in cardiovascular and all cause mortality in clinical trials. Lately, increased incidence of diabetes especially in the high-risk populations using statins has raised the debate whether statins are indicated for primary prevention especially in the metabolic syndrome. Guidelines recommend intensified lifestyle intervention to those in high risk groups on statin therapy to reduce the residual risk. Despite of the proven efficacy on plasma lipids, fibrate, or niacin as monotherapy, or in combination with statins has failed in reducing cardiovascular mortality. This underlies the fact that improvement in dyslipidemia or other biomarkers is not equal to the reduction in cardiovascular events. However, fibrates in combination with statins seem to be beneficial to reduce CVD events in subjects with low HDL-cholesterol (< 0.9–1.1 mmol/L) and elevated triglycerides (> 2.3 mmol/L), but the data are derived from subgroup analysis of clinical trials. The position of niacin and ezetimibe and omega-3 fatty acids in treatment of dyslipidemia in the metabolic syndrome and type 2 diabetes is even less clear and remains to be established in future clinical trials.


Atherosclerosis Cardiovascular risk Coronary heart disease Fibrates High density-lipoprotein Insulin resistance Diabetes Macrovascular complication Metabolic syndrome Nicotinic acid Remnant particle Residual risk Statins Triglyceride Triglyceride-rich lipoprotein Type 2 diabetes Very low-density lipoprotein Dyslipidemia 


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    • Roger VL, Go AS, Lloyd-Jones DM, et al. Executive summary: heart disease and stroke statistics–2012 update: a report from the American Heart Association. Circulation. 2012;125:188–97. This important review highlights the up-to-date development and trends of CVD and risk factors in USA. The statistic summary for 2010 reports that in the U.S. 67% of the adult population has a BMI ≥ 25 and the age-adjusted prevalence of MetS is 34 %. CrossRefPubMedGoogle Scholar
  2. 2.
    Lloyd-Jones DM, Hong Y, Labarthe D, et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic impact goal through 2020 and beyond. Circulation. 2010;121:586–613.CrossRefPubMedGoogle Scholar
  3. 3.
    Turner RC, Millns H, Neil HA, et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ. 1998;316:823–8.CrossRefPubMedGoogle Scholar
  4. 4.
    • Betteridge DJ. Medscape. Lipid control in patients with diabetes mellitus. Nat Rev Cardiol. 2011;8:278–90. A thorough review focusing on lipid abnormalities and treatment of CVD risk in both type 1 and type 2 diabetes. CrossRefPubMedGoogle Scholar
  5. 5.
    Ford ES, Ajani UA, Croft JB, et al. Explaining the decrease in U.S. deaths from coronary disease, 1980–2000. N Engl J Med. 2007;356:2388–98.CrossRefPubMedGoogle Scholar
  6. 6.
    Cholesterol Treatment Trialists' (CTT) Collaborators, Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Peto R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomized trials of statins: a meta-analysis. Lancet. 2008;371:117–25.CrossRefPubMedGoogle Scholar
  7. 7.
    Cooney MT, Dudina A, De Bacquer D, et al. HDL cholesterol protects against cardiovascular disease in both genders, at all ages and at all levels of risk. Atherosclerosis. 2009;206:611–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Goff Jr DC, Gerstein HC, Ginsberg HN, et al. Prevention of cardiovascular disease in persons with type 2 diabetes mellitus: current knowledge and rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol. 2007;99:420.CrossRefGoogle Scholar
  9. 9.
    Taskinen MR. Diabetic dyslipidaemia: from basic research to clinical practice. Diabetologia. 2003;46:733–49.CrossRefPubMedGoogle Scholar
  10. 10.
    Haffner SM, Stern MP, Hazuda HP, et al. Cardiovascular risk factors in confirmed prediabetic individuals. Does the clock for coronary heart disease start ticking before the onset of clinical diabetes? JAMA. 1990;263:2893–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Hu FB, Stampfer MJ, Haffner SM, et al. Elevated risk of cardiovascular disease prior to clinical diagnosis of type 2 diabetes. Diabetes Care. 2002;25:1129–34.CrossRefPubMedGoogle Scholar
  12. 12.
    Adiels M, Olofsson SO, Taskinen MR, Boren J. Diabetic dyslipidaemia. Curr Opin Lipidol. 2006;17:238–46.CrossRefPubMedGoogle Scholar
  13. 13.
    Tota-Maharaj R, Defilippis AP, Blumenthal RS, Blaha MJ. A practical approach to the metabolic syndrome: review of current concepts and management. Curr Opin Cardiol. 2010;25:502–12.CrossRefPubMedGoogle Scholar
  14. 14.
    Zhang H, Dellsperger KC, Zhang C. The link between metabolic abnormalities and endothelial dysfunction in type 2 diabetes: an update. Basic Res Cardiol. 2012;107:1–11.Google Scholar
  15. 15.
    Semenkovich CF. Insulin resistance and atherosclerosis. J Clin Invest. 2006;116:1813–22.CrossRefPubMedGoogle Scholar
  16. 16.
    Natali A, Ferrannini E. Endothelial dysfunction in type 2 diabetes. Diabetologia. 2012;55:1559–63.CrossRefPubMedGoogle Scholar
  17. 17.
    • Mora S, Wenger NK, Demicco DA, et al. Determinants of residual risk in secondary prevention patients treated with high- versus low-dose statin therapy: the Treating to New Targets (TNT) study. Circulation. 2012;125:1979–87. Analysis of the TNT trial data comparing atorvastatin 80 and 10 mg explores risk factors associated with residual risk in statin treated subjects among more than 9000 coronary patients with low LDL-C (<130 mg/dL) on atorvastatin 10 mg. The residual risk correlated with baseline apoproteins, increased BMI, smoking, hypertension, and diabetes indicating multifactorial treatment. CrossRefPubMedGoogle Scholar
  18. 18.
    Gaede P, Valentine WJ, Palmer AJ, et al. Cost-effectiveness of intensified vs conventional multifactorial intervention in type 2 diabetes: results and projections from the Steno-2 study. Diabetes Care. 2008;31:1510–5.CrossRefPubMedGoogle Scholar
  19. 19.
    • Catapano AL, Reiner Z, De Backer G, et al. ESC/EAS Guidelines for the management of dyslipidaemias The task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis. 2011;217 Suppl 1:1–44. The guidelines focus on management of dyslipidemia based on total CVD risk estimation. The treatment targets are given for different risk categories. Evidence-based treatment recommendations cover a wide range of clinical scenarios such as MetS, diabetes, familial dyslipidemias, secondary dyslipidemias, women, and elderly. PubMedGoogle Scholar
  20. 20.
    • Perk J, De Backer G, Gohlke H, et al. for the Authors/Task Force Members of the The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J. 2012;33:1635–701. Latest European guidelines offering a comprehensive diagnostic guidance, risk assessment, and treatment recommendations for primary and secondary CVD prevention. The risk categories are clearly defined and the targets of treatment for dyslipidemias are consistent with the EAS/ESC guidelines. Google Scholar
  21. 21.
    Barter P, Gotto AM, LaRosa JC, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357:1301–10.CrossRefPubMedGoogle Scholar
  22. 22.
    American Diabetes Association. Standards of medical care in diabetes–2012. Diabetes Care. 2012;35 Suppl 1:S11–63.Google Scholar
  23. 23.
    Boekholdt SM, Arsenault BJ, Mora S, et al. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA. 2012;307:1302–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Taskinen MR, Barter PJ, Ehnholm C, et al. Ability of traditional lipid ratios and apolipoprotein ratios to predict cardiovascular risk in people with type 2 diabetes. Diabetologia. 2010;53:1846–55.CrossRefPubMedGoogle Scholar
  25. 25.
    Emerging Risk Factors Collaboration, Di Angelantonio E, Sarwar N, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302:1993–2000.CrossRefPubMedGoogle Scholar
  26. 26.
    Chapman MJ, Ginsberg HN, Amarenco P, et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J. 2011;32:1345–61.CrossRefPubMedGoogle Scholar
  27. 27.
    Sarwar N, Danesh J, Eiriksdottir G, et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2007;115:450–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298:299–308.CrossRefPubMedGoogle Scholar
  29. 29.
    Bansal S, Buring JE, Rifai N, et al. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA. 2007;298:309–16.CrossRefPubMedGoogle Scholar
  30. 30.
    Sarwar N, Sandhu MS, et al. Triglyceride coronary disease genetics consortium and emerging risk factors collaboration, triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet. 2010;375:1634–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35:1364–79.CrossRefPubMedGoogle Scholar
  32. 32.
    • Cholesterol Treatment Trialists' (CTT) Collaboration, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81. This study assessed the relation of genetically raised triglyceride concentration and risk of CVD in a cohort of 73252 individuals with genetic analyses. Authors show that elevated TG concentrations due to a specific genetic variation in apoA5 gene, that regulates planned triglyceride concentration, are independently associated with CHD in a dose-dependent manner. Mean difference in TG concentration per observed C-allele was 0.25 mmol/L, instead, LDL-C, HDL-C, and apoB-concentrations were similar. Furthermore, C-allele carriers had higher levels of small dense LDL, VLDL particles, and small HDL particles compared with the wild haplotype. The authors conclude that a relationship exists between triglyceride mediated pathways and coronary heart disease. CrossRefPubMedGoogle Scholar
  33. 33.
    • Mihaylova B, Emberson J, Blackwell L, et al. for the Cholesterol Treatment Trialists’ (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomized trials. Lancet. 2012;380:581–90. A meta-analysis including data from 22 trials of statin treatment (n = 134537) and 5 trials of more vs less statin (n = 39612). In individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in LDL-C produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. Since benefits greatly exceed any known hazards of statin therapy, the authors suggest that the guidelines might need to be reconsidered among low-risk population. Google Scholar
  34. 34.
    • Kostis WJ, Cheng JQ, Dobrzynski JM, et al. Meta-analysis of statin effects in women vs men. J Am Coll Cardiol. 2012;59:572–82. A meta-analysis including data from 18 statin trials with sex-specific outcomes. The benefits of statin treatment were significant in both women and men in primary and secondary prevention irrespective of baseline risk, used treatment or type of endpoint studied. CrossRefPubMedGoogle Scholar
  35. 35.
    Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364:685–96.CrossRefPubMedGoogle Scholar
  36. 36.
    Knopp RH, d' Emden M, Smilde JG, Pocock SJ. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points 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;29:1478–85.CrossRefPubMedGoogle Scholar
  37. 37.
    Wanner C, Krane V, Marz W, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353:238–48.CrossRefPubMedGoogle Scholar
  38. 38.
    Shepherd J, Barter P, Carmena R, et al. Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating to New Targets (TNT) study. Diabetes Care. 2006;29:1220–6.CrossRefPubMedGoogle Scholar
  39. 39.
    Collins R, Armitage J, Parish S, et al. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361:2005–16.CrossRefPubMedGoogle Scholar
  40. 40.
    Sattar N, Gaw A, Scherbakova O, et al. Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation. 2003;108:414–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Clearfield M, Downs JR, Lee M, et al. Implications from the Air Force/Texas Coronary Atherosclerosis Prevention Study for the Adult Treatment Panel III guidelines. Am J Cardiol. 2005;96:1674–80.CrossRefPubMedGoogle Scholar
  42. 42.
    Ridker PM, MacFadyen JG, Fonseca FA, et al. Number needed to treat with rosuvastatin to prevent first cardiovascular events and death among men and women with low low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein: justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin (JUPITER). Circ Cardiovasc Qual Outcomes. 2009;2:616–23.CrossRefPubMedGoogle Scholar
  43. 43.
    Ridker PM, Danielson E, Fonseca FA, et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet. 2009;373:1175–82.CrossRefPubMedGoogle Scholar
  44. 44.
    Pedersen TR, Kjekshus J, Berg K, et al. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383–9.Google Scholar
  45. 45.
    Girman CJ, Rhodes T, Mercuri M, et al. The metabolic syndrome and risk of major coronary events in the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Am J Cardiol. 2004;93:136–41.CrossRefPubMedGoogle Scholar
  46. 46.
    Deedwania P, Barter P, Carmena R, et al. Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the treating to new targets study. Lancet. 2006;368:919–28.CrossRefPubMedGoogle Scholar
  47. 47.
    Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled tria. Lancet. 2003;361:1149–58.CrossRefPubMedGoogle Scholar
  48. 48.
    •• Taskinen MR, Adiels M, Westerbacka J, et al. Dual metabolic defects are required to produce hypertriglyceridemia in obese subjects. Arterioscler Thromb Vasc Biol. 2011;31:2144–50. A paper studying apoB and TG kinetics utilizing stable isotopes in obese normoTG and hyperTG men matched for BMI and waist circumference compared with lean normoTG men. Obese hyper TG men have increased production and decreased removal rates of large VLDL particle together with increases of liver fat content and apo CIII levels. The authors demonstrate that VLDL1 secretion rate is driven by liver fat content whereas the catabolic rate of large VLDL particles are inversely correlated with apo CIII levels. Thus, dual metabolic defects are requested to produce hypertriglyceridemia in obese men. CrossRefPubMedGoogle Scholar
  49. 49.
    Fabbrini E, Mohammed BS, Korenblat KM, et al. Effect of fenofibrate and niacin on intrahepatic triglyceride content, very low-density lipoprotein kinetics, and insulin action in obese subjects with nonalcoholic fatty liver disease. J Clin Endocrinol Metab. 2010;95:2727–35.CrossRefPubMedGoogle Scholar
  50. 50.
    Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.CrossRefPubMedGoogle Scholar
  51. 51.
    •• Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375:735–42. The first meta-analysis of studies on diabetogenic potential of statins. This paper launched the discussion of new onset diabetes being a side-effect of statins and statin use in primary prevention. CrossRefPubMedGoogle Scholar
  52. 52.
    Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011;305:2556–64.CrossRefPubMedGoogle Scholar
  53. 53.
    •• Waters DD, Ho JE, Demicco DA, et al. Predictors of new-onset diabetes in patients treated with atorvastatin results from 3 large randomized clinical trials. J Am Coll Cardiol. 2011;57:1535–45. A meta-analysis of TNT, IDEAL, and SPARCL trials reporting that baseline fasting blood glucose, body mass index, hypertension, and fasting triglycerides are independent predictors of new-onset T2D during statin treatment. Patients without these risk factors had a diabetes risk of 2% or less in each trial, and those with 1 risk factor had a risk of 4% to 5%. When 3 or 4 of the risk factors were present the risk of new-onset T2D exceeded 10%. CrossRefPubMedGoogle Scholar
  54. 54.
    • Sattar N, Taskinen M. Statins are diabetogenic–myth or reality? Atheroscler. Suppl. 2012;13:1–10. An updated review highlighting the current available evidence related to new-onset diabetes as a side-effect of statins and the potential mechanisms of this association. Google Scholar
  55. 55.
    Keech A, Simes RJ, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366:1849–61.CrossRefPubMedGoogle Scholar
  56. 56.
    Scott R, O'Brien R, Fulcher G, et al. Effects of fenofibrate treatment on cardiovascular disease risk in 9795 individuals with type 2 diabetes and various components of the metabolic syndrome: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetes Care. 2009;32:493–8.CrossRefPubMedGoogle Scholar
  57. 57.
    Jun M, Foote C, Lv J, et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet. 2010;375:1875–84.CrossRefPubMedGoogle Scholar
  58. 58.
    Steiner G, Hamsten A, Hosking J, et al. for the 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;357:905–10.Google Scholar
  59. 59.
    Meade T, Zuhrie R, Cook C, Cooper J. Bezafibrate in men with lower extremity arterial disease: randomised controlled trial. BMJ. 2002;325:1139.CrossRefPubMedGoogle Scholar
  60. 60.
    Emmerich KH, Poritis N, Stelmane I, et al. Efficacy and safety of etofibrate in patients with non-proliferative diabetic retinopathy. Klin Monbl Augenheilkd. 2009;226:561–7.CrossRefPubMedGoogle Scholar
  61. 61.
    ACCORD Study Group, Ginsberg HN, Elam MB, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362:1563–74.CrossRefPubMedGoogle Scholar
  62. 62.
    Sacks FM, Carey VJ, Fruchart JC. Combination lipid therapy in type 2 diabetes. N Engl J Med. 2010;363:692–4. author reply 694–5.CrossRefPubMedGoogle Scholar
  63. 63.
    Bruckert E, Labreuche J, Deplanque D, et al. Fibrates effect on cardiovascular risk is greater in patients with high triglyceride levels or atherogenic dyslipidemia profile: a systematic review and meta-analysis. J Cardiovasc Pharmacol. 2011;57:267–72.CrossRefPubMedGoogle Scholar
  64. 64.
    Lee M, Saver JL, Towfighi A, et al. Efficacy of fibrates for cardiovascular risk reduction in persons with atherogenic dyslipidemia: a meta-analysis. Atherosclerosis. 2011;217:492–8.CrossRefPubMedGoogle Scholar
  65. 65.
    Awan Z, Seidah NG, MacFadyen JG, et al. Rosuvastatin, proprotein convertase subtilisin/kexin type 9 concentrations, and LDL cholesterol response: the JUPITER trial. Clin Chem. 2012;58:183–9.CrossRefPubMedGoogle Scholar
  66. 66.
    Farnier M. The role of proprotein convertase subtilisin/kexin type 9 in hyperlipidemia: focus on therapeutic implications. Am J Cardiovasc Drugs. 2011;11:145–52.CrossRefPubMedGoogle Scholar
  67. 67.
    Rosenblit PD. Do persons with diabetes benefit from combination statin and fibrate therapy? Curr Cardiol Rep. 2012;14:112–24.CrossRefPubMedGoogle Scholar
  68. 68.
    Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986;8:1245–55.CrossRefPubMedGoogle Scholar
  69. 69.
    Chapman MJ, Redfern JS, McGovern ME, Giral P. Niacin and fibrates in atherogenic dyslipidemia: pharmacotherapy to reduce cardiovascular risk. Pharmacol Ther. 2010;126:314–45.CrossRefPubMedGoogle Scholar
  70. 70.
    Boden WE, Probstfield JL, et al. AIM-HIGH Investigators; niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255–67.CrossRefPubMedGoogle Scholar
  71. 71.
    Leiter LA, Betteridge DJ, Farnier M, et al. Lipid-altering efficacy and safety profile of combination therapy with ezetimibe/statin vs statin monotherapy in patients with and without diabetes: an analysis of pooled data from 27 clinical trials. Diabetes Obes Metab. 2011;13:615–28.CrossRefPubMedGoogle Scholar
  72. 72.
    Fleg JL, Mete M, Howard BV, et al. Effect of statins alone vs statins plus ezetimibe on carotid atherosclerosis in type 2 diabetes: the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial. J Am Coll Cardiol. 2008;52:2198–205.CrossRefPubMedGoogle Scholar
  73. 73.
    Baigent C, Landray M, Reith T, et al. for the Sharp Collaborative Group. Study of Heart and Renal Protection (SHARP): randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9438 patients with chronic kidney disease. Am Heart J. 2010;160:785–94.e10.CrossRefGoogle Scholar
  74. 74.
    Harris WS, Miller M, Tighe AP, et al. Omega-3 fatty acids and coronary heart disease risk: clinical and mechanistic perspectives. Atherosclerosis. 2008;197:12–24.CrossRefPubMedGoogle Scholar
  75. 75.
    Skulas-Ray AC, Kris-Etherton PM, Harris WS, et al. Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia. Am J Clin Nutr. 2011;93:243–52.CrossRefPubMedGoogle Scholar
  76. 76.
    Kromhout D, Yasuda S, Geleijnse JM, Shimokawa H. Fish oil and omega-3 fatty acids in cardiovascular disease: do they really work? Eur Heart J. 2012;33:436–43.CrossRefPubMedGoogle Scholar
  77. 77.
    Abeywardena MY, Patten GS. Role of Omega3 Longchain polyunsaturated fatty acids in reducing cardio-metabolic risk factors. Endocrin Metab Immune Disord Drug Targets. 2011;11:232–46.Google Scholar
  78. 78.
    Wierzbicki AS, Clarke RE, Viljoen A, Mikhailidis DP. Triglycerides: a case for treatment? Curr Opin Cardiol. 2012;27:398–404.CrossRefPubMedGoogle Scholar
  79. 79.
    • Kwak SM, Myung SK, Lee YJ, et al. Efficacy of Omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials. Arch Intern Med. 2012;172:686–94. A thorough meta-analysis of 13 RCTs demonstrating insufficient evidence of omega-3 fatty acid supplements to reduce overall cardiovascular events in patients with a history of cardiovascular disease. CrossRefPubMedGoogle Scholar
  80. 80.
    • The ORIGIN Trial Investigators. n-3 Fatty Acids and Cardiovascular Outcomes in Patients with Dysglycemia. N Engl J Med. 2012. Latest large outcome trial testing lipid lowering in glycemic subjects to reduce CVD endpoints. Supplementation with 1 g of omega-3 fatty acids did not affect CVD mortality, death from arrhythmia, or rates of major cardiovascular events compared with among over 12.000 subjects with dysglycemia and additional risk factors and therefore at high risk for T2D. About half of the study population received statins. Google Scholar
  81. 81.
    Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109–22.CrossRefPubMedGoogle Scholar
  82. 82.
    Barter PJ, Rye KA, Tardif JC, et al. Effect of torcetrapib on glucose, insulin, and hemoglobin A1c in subjects in the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial. Circulation. 2011;124:555–62.CrossRefPubMedGoogle Scholar
  83. 83.
    •• Drew BG, Rye KA, Duffy SJ, et al. The emerging role of HDL in glucose metabolism. Nat Rev Endocrinol. 2012;8:237–45. A thorough review discussing the emerging role of HDL in glucose metabolism and potential therapeutic options achieved by raising HDL. The authors highlight that classical anti-atherogenic and anti-inflammatory properties as well as other actions of HDL may affect insulin secretion from the β-cell, direct glucose uptake by the muscle, and insulin sensitivity. CrossRefPubMedGoogle Scholar
  84. 84.
    • Fryirs MA, Barter PJ, Appavoo M, et al. Effects of high-density lipoproteins on pancreatic beta-cell insulin secretion. Arterioscler Thromb Vasc Biol. 2010;30:1642–8. This study utilized rat primary islets and Min6 cell to examine in vitro the effects of human HDL to stimulate insulin secretion in a ABCG1-dependent mechanism, both in basal, and high-glucose conditions. The key finding was that HDL as well as apoproteins apoA-I and apoA-II increased β-cell insulin secretion. The authors suggest that raising HDL levels may be beneficial in T2D. CrossRefPubMedGoogle Scholar
  85. 85.
    Liu K, Daviglus ML, Loria CM, et al. Healthy lifestyle through young adulthood and the presence of low cardiovascular disease risk profile in middle age: the Coronary Artery Risk Development in (Young) Adults (CARDIA) study. Circulation. 2012;125:996–1004.CrossRefPubMedGoogle Scholar
  86. 86.
    • Laitinen TT, Pahkala K, Magnussen CG, et al. Ideal cardiovascular health in childhood and cardiometabolic outcomes in adulthood: the cardiovascular risk in young Finns study. Circulation. 2012;125:1971–8. A 21-year follow-up data from the Cardiovascular Risk in Young Finns Study cohort demonstrate that the number of ideal cardiovascular health metrics present in childhood is associated with reduced risk of hypertension, MetS, high LDL-C, and high-risk carotid artery intima-media thickness in young adulthood. The outcome is not affected by adjustment with age, sex, or socioeconomic status. CrossRefPubMedGoogle Scholar
  87. 87.
    Seidah NG, Prat A. The biology and therapeutic targeting of the proprotein convertases. Nat Rev Drug Discov. 2012;11:367–83.CrossRefPubMedGoogle Scholar
  88. 88.
    Chan DC, Watts GF. Dyslipidaemia in the metabolic syndrome and type 2 diabetes: pathogenesis, priorities, pharmacotherapies. Expert Opin Pharmacother. 2011;12:13–30.CrossRefPubMedGoogle Scholar
  89. 89.
    Xiao C, Hsieh J, Adeli K, Lewis GF. Gut-liver interaction in triglyceride-rich lipoprotein metabolism. Am J Physiol Endocrinol Metab. 2011;301:E429–46.CrossRefPubMedGoogle Scholar
  90. 90.
    Karpe F, Dickmann JR, Frayn KN. Fatty acids, obesity, and insulin resistance: time for a reevaluation. Diabetes. 2011;60:2441–9.CrossRefPubMedGoogle Scholar
  91. 91.
    Chapman MJ, Ginsberg HN, Amarenco P, et al. for the European Atherosclerosis Society Consensus Panel. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J. 2011;32:1345–61.Google Scholar
  92. 92.
    Hassing HC, Mooij H, Guo S, et al. Inhibition of hepatic sulfatase-2 in vivo: a novel strategy to correct diabetic dyslipidemia. Hepatology. 2012;55:1746–53.CrossRefPubMedGoogle Scholar
  93. 93.
    Grundy SM, Becker D, Clark LT, et al. for the 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). Circulation. 2002;106:3143–3421.Google Scholar
  94. 94.
    Conroy RM, Pyorala K, Fitzgerald AP, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. 2003;24:987–1003.CrossRefPubMedGoogle Scholar
  95. 95.
    ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The antihypertensive and lipid-lowering treatment to prevent heart attack trial. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA. 2002;288:2998–3007.CrossRefGoogle Scholar
  96. 96.
    de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA. 2004;292:1307–16.CrossRefPubMedGoogle Scholar
  97. 97.
    Pedersen TR, Faergeman O, Kastelein JJ, et al. Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) Study Group. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005;294:2437–45.CrossRefPubMedGoogle Scholar
  98. 98.
    Nakamura H, Itakura A, Goto A, et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomized controlled trial. Lancet. 2006;368:1155–63.Google Scholar
  99. 99.
    Kjekshus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007;357:2248–61.CrossRefPubMedGoogle Scholar
  100. 100.
    Gissi-HF I, Tavazzi L, Maggioni AP, et al. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:1231–9.CrossRefGoogle Scholar
  101. 101.
    Armitage J, Bowman L, Wallendszus K, et al. for the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group. Intensive lowering of LDL cholesterol with 80 mg vs 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet. 2010;376:1658–69.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Medicine, Division of EndocrinologyHelsinki University Central Hospital, University of HelsinkiHelsinkiFinland
  2. 2.Department of Medicine, Division of CardiologyHelsinki University Central Hospital, University of HelsinkiHelsinkiFinland

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