Reducing residual vascular risk in patients with atherogenic dyslipidemia: Where do we go from here?

Clinical Lipidology

Volumn 5, Issue 6, 2010, Pages 811-826

  Hermans, Michel P ^a   Fruchart, Jean Charles ^b  

^a CLINIQUES UNIVERSITAIRES SAINT LUC   (Belgium)

^b Fondation Cæur and Artères   (France)

Author keywords

apoB; cardiovascular; diabetes; HDL C; insulin resistance; metabolic syndrome; microangiopathy; residual risk; triglyceride; VLDL

Indexed keywords

APOLIPOPROTEIN A1; APOLIPOPROTEIN B100; EZETIMIBE; FENOFIBRATE; FIBRIC ACID DERIVATIVE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INSULIN; LAROPIPRANT PLUS NICOTINIC ACID; LOW DENSITY LIPOPROTEIN CHOLESTEROL; NICOTINIC ACID; SIMVASTATIN; TRIACYLGLYCEROL; VERY LOW DENSITY LIPOPROTEIN CHOLESTEROL;

ATHEROSCLEROSIS; CARDIOVASCULAR RISK; DIABETIC ANGIOPATHY; DIABETIC MICROANGIOPATHY; DIABETIC NEPHROPATHY; DIABETIC RETINOPATHY; DIET THERAPY; DISEASE SEVERITY; DYSLIPIDEMIA; EXERCISE; HIGH RISK PATIENT; HUMAN; HYPERCHOLESTEROLEMIA; HYPERINSULINEMIA; HYPERTRIGLYCERIDEMIA; INSULIN RESISTANCE; LIFESTYLE MODIFICATION; METABOLIC SYNDROME X; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK REDUCTION;

EID: 79952125432     PISSN: 17460875     EISSN: None     Source Type: Journal    
DOI: 10.2217/clp.10.65     Document Type: Review

References (134)

1. Libby PL: The forgotten majority. Unfinished business in cardiovascular risk reduction. J. Am. Coll. Cardiol. 46, 1225-1228 (2005).
2. Fruchart J-C, Sacks F, Hermans MP et al.: Executive statement: the Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidemic patients. A condensed position paper by the Residual Risk Reduction Initiative (R3i). Diab. Vasc. Dis. Res. 5, 319-335 (2008).
3. Fruchart J-C, Sacks F, Hermans MP et al.; for the Residual Risk Reduction Initiative: The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia. Am. J. Cardiol. 102(Suppl.), 1-34 (2008).
4. Jones PH: Expert perspective: reducing cardiovascular risk in metabolic syndrome and Type 2 diabetes mellitus beyond low-density lipoprotein cholesterol lowering. Am. J. Cardiol. 102, 41L-47L (2008).
5. Grundy SM, Cleeman JI, Merz CN et al.: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 110, 227-239 (2004). (Pubitemid 38924592)
6. Grundy SM, Cleeman JI, Daniels SR et al.; American Heart Association; National Heart, Lung, and Blood Institute: Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112, 2735-2752 (2005). (Pubitemid 41532612)
7. Graham I, Atar D, Borch-Johnsen K et al.; European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG): European guidelines on cardiovascular disease prevention in clinical practice. Fourth Joint Task Force of the European Society of Cardiology and other Societies on Cardiovascular Disease Prevention in Clinical Practice. Executive summary. Eur. Heart J. 28, 2375-2414 (2007). (Pubitemid 47542237)
8. Ryden L, Standl E, Bartnik M et al.: Guidelines on diabetes, prediabetes, and cardiovascular diseases: executive summary. The 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). Eur. Heart J. 28, 88-136 (2007). (Pubitemid 46137814)
9. Brunzell JD, Davidson M, Furberg CD et al.: Lipoprotein management in patients with cardiometabolic risk: consensus conference report from the American Diabetes Association and the American College of Cardiology Foundation. J. Am. Coll. Cardiol. 51, 1512-1524 (2008). (Pubitemid 351470037)
10. American Diabetes Association: Clinical practice recommendations. Diabetes Care 33, S1-S100 (2010).
11. Dodson PM: Diabetes and the Eye. In: Diabetic Retinopathy. Dodson PM (Ed.). Oxford University Press, Oxford, UK (2009).
12. Tesfaye S, Chaturvedi N, Eaton SE et al.; EURODIAB Prospective Complications Study Group: Vascular risk factors and diabetic neuropathy. N. Engl. J. Med. 352, 341-350 (2005).
13. Hermans MP: Diabetic macro- and microvascular disease in Type 2 diabetes. Diabetes Vasc. Dis. Res. 4, S7-S11 (2007). (Pubitemid 47121957)
14. Hermans MP, Ahn SA, Rousseau MF: Erectile dysfunction, microangiopathy and UKPDS risk in Type 2 diabetes. Diabetes Metab. 35, 484-489 (2009).
15. Rajamani K, Colman PG, Li LP et al.; FIELD study investigators: Effect of fenofibrate on amputation events in people with Type 2 diabetes mellitus (FIELD study): a prespecified analysis of a randomised controlled trial. Lancet 373, 1780-1788 (2009).
16. Chew EY, Ambrosius WT, Howard LT et al.; ACCORD Study Group: Rationale, design, and methods of the Action to Control Cardiovascular Risk in Diabetes Eye Study (ACCORD-EYE). Am. J. Cardiol. 99(12A), 103I-111I (2007).
17. Friedewald VE Jr, Ballantyne CM, Davidson MH, Guyton JR, Roberts WC: The editor's roundtable: lipid management beyond statins - reducing residual cardiovascular risk. Am. J. Cardiol. 102, 559-567 (2008).
18. Fruchart JC, Nierman MC, Stroes ES, Kastelein JJ, Duriez P: New risk factors for atherosclerosis and patient risk assessment. Circulation 109(23 Suppl. 1), III15-III19 (2004). (Pubitemid 38786438)
19. Assmann G, Cullen P, Fruchart JC et al.: International Task Force for Prevention of Coronary Heart Disease: implications of emerging risk factors for therapeutic intervention. Nutr. Metab. Cardiovasc. Dis. 15, 373-381 (2005). (Pubitemid 41578783)
20. Yusuf S, Hawken S, Ôunpuu S et al.; on behalf of the INTERHEART investigators: Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364, 937-952 (2004). (Pubitemid 39208455)
21. Brown G, Albers JJ, Fisher LD et al.: Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N. Engl. J. Med. 323, 1289-1298 (1990). (Pubitemid 20364735)
22. HPS Collaborative Group: MRC/BHF Heart Protection Study of Cholesterol- Lowering with Simvastatin in 5,963 People with Diabetes: a randomised placebo-controlled trial. Lancet 361, 2005-2016 (2003).
23. Sacks FM, Tonkin AM, Shepherd J et al.: Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project. Circulation 102, 1893-1900 (2000).
24. Colhoun HM, Betteridge DJ, Durrington PN et al.; 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 364, 685-696 (2004). (Pubitemid 39140624)
25. LaRosa JC, Grundy SM, Waters DD et al.: Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N. Engl. J. Med. 352, 1425-1435 (2005). (Pubitemid 40471450)
26. Shepherd J, Barter P, Carmena R et al.; Treating to New Targets Investigators: 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 29, 1220-1226 (2006). (Pubitemid 44125913)
27. Ridker PM, Danielson E, Fonseca FA et al.; JUPITER Study Group: Rosuvastatin to prevent vascular events in men and women with elevated C-reative protein. N. Engl. J. Med. 359, 2195-2207 (2008).
28. Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M: Mortality from coronary heart disease in subjects with Type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N. Engl. J. Med. 339, 229-234 (1998). (Pubitemid 28350165)
29. Juutilainen A, Lehto S, Rönnemaa T, Pyörälä K, Laakso M: Type 2 diabetes as a 'coronary heart disease equivalent'. An 18 year prospective population-based study in Finnish subjects. Diabetes Care 28, 2901-2907 (2005). (Pubitemid 43942922)
30. Buyken AE, von Eckardstein A, Schulte H, Cullen P, Assmann G: Type 2 diabetes mellitus and risk of coronary heart disease: results of the 10-year follow-up of the PROCAM study. Eur. J. Cardiovasc. Prev. Rehabil. 14, 230-236 (2007). (Pubitemid 46650078)
31. Mazzone T, Chait A, Plutzky J: Cardiovascular disease risk in Type 2 diabetes mellitus: insights from mechanistic studies. Lancet 371, 1800-1809 (2008). (Pubitemid 351697956)
32. Schramm TK, Gislason GH, Køber L et al.: Diabetes patients requiring glucose-lowering therapy and nondiabetics with a prior myocardial infarction carry the same cardiovascular risk: a population study of 3.3 million people. Circulation 117, 1945-1954 (2008). (Pubitemid 351543470)
33. Ferrieres J, Tocque-Le Gousse E, Fabry C, Hermans MP; on behalf of the French CEPHEUS investigators: Assessment of lipid-lowering treatment in France. Arch. Cardiovasc. Dis. 101, 557-563 (2008).
34. Hermans MP, Castro Cabezas M, Strandberg T et al.: Centralized pan- European survey on the under-treatment of hypercholesterolaemia (CEPHEUS): overall findings from eight countries. Curr. Med. Res. Opin. 26, 445-454 (2010).
35. Manninen V, Tenkanen L, Koskinen P et al.: Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Implications for treatment. Circulation 85 37-45 (1992).
36. Davignon J, Cohn JS: Triglycerides: a risk factor for coronary heart disease. Atherosclerosis 124(Suppl.) S57-S64 (1996).
37. Brites FD, Bonavita CD, De Geitere C et al.: Alterations in the main steps of reverse cholesterol transport in male patients with primary hypertriglyceridemia and low HDL-cholesterol levels. Atherosclerosis 152, 181-192 (2000).
38. Fruchart JC, Duriez P: HDL and triglyceride as therapeutic targets. Curr. Opin. Lipidol. 13, 605-616 (2002). (Pubitemid 36009199)
39. Kathiresan S, Otvos JD, Sullivan LM et al.: Increased small low-density lipoprotein particle number. A prominent feature of the metabolic syndrome in the Framingham Heart Study. Circulation 113, 20-29 (2006). (Pubitemid 43958484)
40. Alsheikh-Ali AA, Lin JL, Abourjaily P, Ahearn D, Kuvin JT, Karas RH: 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. 100, 1499-1501 (2007). (Pubitemid 350050854)
41. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM: Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA 298, 309-316 (2007). (Pubitemid 47080485)
42. Barter P, Gotto AM, LaRosa JC et al.; Treating to New Targets Investigators: HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N. Engl. J. Med. 357, 1301-1310 (2007). (Pubitemid 47481452)
43. Miller M, Cannon CP, Murphy SA, Qin J, Ray KK, Braunwald E; PROVE-IT TIMI 22 Investigators: Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE-IT TIMI 22 trial. J. Am. Coll. Cardiol. 51, 724-730 (2008). (Pubitemid 351221217)
44. Rana JS, Visser ME, Arsenault BJ et al.: Metabolic dyslipidemia and risk of future coronary heart disease in apparently healthy men and women: The EPIC-Norfolk prospective population study. Int. J. Cardiol. 143(3), 399-404 (2010).
45. Assmann G, Cullen P, Schulte H: Non-LDL-related dyslipidemia and coronary risk: a case-control study. Diab. Vasc. Dis. Res. 7, 204-212 (2010).
46. Labreuche J, Deplanque D, Touboul PJ, Bruckert E, Amarenco P: Association between change in plasma triglyceride levels and risk of stroke and carotid atherosclerosis systematic review and meta-regression analysis. Atherosclerosis 212(1), 9-15(2010).
47. Sarwar N, Sandhu MS, Ricketts SL et al.: Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet 375, 1634-1639 (2010).
48. Garvey WT, Kwon S, Zheng D et al.: Effects of insulin resistance and Type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes 52, 453-462 (2003). (Pubitemid 36173203)
49. Adiels M, Olofsson S-O, Taskinen M-R, Borén J: Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome. Arterioscler. Thromb. Vasc. Biol. 28, 1225-1236 (2008).
50. Lteif A, Mather K: Insulin resistance, metabolic syndrome and vascular diseases: update and mechanistic linkages. Can. J. Cardiol. 20(Suppl. B), 66B-76B (2004).
51. Assmann G, Schulte H, Seedorf U: Cardiovascular risk assessment in the metabolic syndrome: results from the Prospective Cardiovascular Munster (PROCAM) Study. Int. J. Obes. (Lond.) 32(Suppl. 2), S11-S16 (2008). (Pubitemid 351671296)
52. Bonora E, Targher G, Formentini G et al.: The metabolic syndrome is an independent predictor of cardiovascular disease in Type 2 diabetic subjects. Prospective data from the Verona Diabetes Complications Study. Diabet. Med. 21, 52-58 (2004). (Pubitemid 38168029)
53. Bruno G, Merletti F, Biggeri A et al.: Metabolic syndrome as a predictor of all-cause and cardiovascular mortality in Type 2 diabetes: the Casale Monferrato Study. Diabetes Care 27, 2689-2694 (2004). (Pubitemid 39441471)
54. Metascreen Writing Committee: The metabolic syndrome is a risk indicator of microvascular and macrovascular complications in diabetes. Results from Metascreen, a multicenter diabetes clinic-based survey. Diabetes Care 29, 2701-2707 (2006).
55. Cull CA, Jensen CC, Retnakaran R, Holman RR: Impact of the metabolic syndrome on macrovascular and microvascular outcomes in Type 2 diabetes mellitus: United Kingdom Prospective Diabetes Study 78. Circulation 116, 2119-2126 (2007). (Pubitemid 350060349)
56. Sadikot SM, Misra A: The metabolic syndrome: an exercise in utility or futility? Diabetes Metab. Syndr. Clin. Res. Rev. 1, 3-21 (2007). (Pubitemid 46722235)
57. Alberti KG, Eckel RH, Grundy SM et al.: Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120, 1640-1645 (2009).
58. Hermans MP, Ahn SA, Amoussou-Guenou KD, Rousseau MF: Impact of metabolic syndrome on microvascular complications in Type 2 diabetes. Diab. Metab. Syndr. 4(3), 150-154 (2010).
59. Sadikot S, Hermans MP: Here we go again The metabolic syndrome revisited! Diab. Metab. Syndr. 4, 111-120 (2010).
60. Davis RA: Cell and molecular biology of the assembly and secretion of apolipoprotein B-containing lipoproteins by the liver. Biochim. Biophys. Acta 1440, 1-31 (1999). (Pubitemid 29406146)
61. Blasiole DA, Davis RA, Attie AD: The physiological and molecular regulation of lipoprotein assembly and secretion. Mol. Biosyst. 3, 608-619 (2007). (Pubitemid 47258227)
62. Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem. 18, 499-502 (1972).
63. Walldius G, Jungner I, Holme I, Aastveit AH, Kolar W, Steiner E: High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet 358, 2026-2033 (2001). (Pubitemid 34084825)
64. Lu W, Resnick HE, Jablonski KA et al.: Non-HDL cholesterol as a predictor of cardiovascular disease in Type 2 diabetes: The Strong Heart Study. Diab. Care 26, 16-23 (2003). (Pubitemid 36928989)
65. Denke MA: Weighing in before the fight. Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol versus apolipoprotein B as the best predictor for coronary heart disease and the best measure of therapy. Circulation 112, 3368-3370 (2005).
66. Pischon T, Girman GJ, Sacks FM, Rifai N, Stampfer NJ, Rimm EB: Non-high-density lipoprotein cholesterol and apolipoprotein B in the prediction of coronary heart disease in men, Circulation 112, 3375-3383 (2005). (Pubitemid 43739551)
67. Sniderman AD: Apolipoprotein B versus non-high-density lipoprotein cholesterol. And the winner is Circulation 112, 3366-3367 (2005). (Pubitemid 43739547)
68. Ahmad J, Khan AR, Ahmed F, Siddiqui S: Non-HDL cholesterol versus apolipoprotein B in the identification of dyslipidemic phenotypes associated with cardiovascular risk in Type 2 diabetic dyslipoproteinemia. Diab. Metab. Syndr. 1, 29-36 (2007). (Pubitemid 46696576)
69. Hermans MP, Ahn SA, Rousseau MF: The non-HDL-C/HDL-C ratio provides cardiovascular risk stratification similar to the ApoB/ApoA1 ratio in diabetics: Comparison with reference lipid markers. Diab. Metab. Syndr. 1, 23-28 (2007). (Pubitemid 46696577)
70. Sulkes D, Brown BG, Krauss RM, Segrest JP, Sniderman AD, Roberts WC: The editor's roundtable: expanded versus standard lipid panels in assessing and managing cardiovascular risk. Am. J. Cardiol. 101, 828-842 (2008).
71. Rosenson RS: Management of non-high-density lipoprotein abnormalities. Atherosclerosis 207, 328-335 (2009).
72. Kawakami A, Osaka M, Tani M et al.: Apolipoprotein CIII links hyperlipidemia with vascular endothelial cell dysfunction. Circulation 118, 731-742 (2008).
73. Mendivil CO, Zheng C, Furtado J, Lel J, Sacks FM: Metabolism of very-low-density lipoprotein and low-density lipoprotein containing apolipoprotein C-III and not other small apolipoproteins. Arterioscler. Thromb. Vasc. Biol. 30, 239-245 (2010).
74. Zheng C, Khoo C, Furtado J, Sacks FM: Apolipoprotein C-III and the metabolic basis for hypertriglyceridemia and the dense low-density lipoprotein phenotype. Circulation 121, 1722-1734 (2010).
75. Kannel WB, Vasan RS, Keyes MJ, Sullivan LM, Robins SJ: Usefulness of the triglyceride-high-density lipoprotein versus the cholesterol-high-density lipoprotein ratio for predicting insulin resistance and cardiometabolic risk (from the Framingham Offspring Cohort). Am. J. Cardiol. 101, 497-501 (2008). (Pubitemid 351199440)
76. da Luz PL, Favarato D, Faria-Neto JR Jr, Lemos P, Chagas AC: High ratio of triglycerides to HDL-Cholesterol predicts extensive coronary disease. Clinics (Sao Paulo) 63, 427-432 (2008).
77. Bittner V, Johnson BD, Zineh I et al.: The triglyceride/high-density lipoprotein cholesterol ratio predicts all-cause mortality in women with suspected myocardial ischemia: a report from the Women's Ischemia Syndrome Evaluation (WISE). Am. Heart J. 157, 548-555 (2009).
78. Cordero A, Andrés E, Ordoñez B et al.; MESYAS (Metabolic Syndrome Active Subjects) Study Investigators: usefulness of triglycerides-to-high-density lipoprotein cholesterol ratio for predicting the first coronary event in men. Am. J. Cardiol. 104, 1393-1397 (2009).
79. Ginsberg HN, Elam MB, Lovato LC et al.; ACCORD Study Group: Effects of combination lipid therapy in Type 2 diabetes mellitus. N. Engl. J. Med. 362, 1563-1574 (2010).
80. Fruchart J-C, Sacks FM, Hermans MP: Implications of the ACCORD lipid study: perspective from the Residual Risk Reduction Initiative (R3i). Curr. Med. Res. Opin. 26, 1793-1797 (2010).
81. Sumner AE, Vega GL, Genovese DJ, Finley KB, Bergman RN, Boston RC: Normal triglyceride levels despite insulin resistance in African Americans: role of lipoprotein lipase. Metabolism 54, 902-909 (2005). (Pubitemid 40827206)
82. Dehout F, Haumont S, Gaham N, Amoussou-Guenou KD, Hermans MP: Metabolic syndrome in Bantu subjects with Type 2 diabetes from sub-Saharan extraction: prevalence, gender differences and HOMA-hyperbolic product. Diab. Metab. Syndr. 2, 5-11 (2008). (Pubitemid 351209310)
83. Munoko TH, Hermans MP: Phenotypic characterization of first generation Maghrebian migrants with Type 2 diabetes: a gender-based comparison with a reference North-Caucasian Belgian cohort. Diab. Met. Syndr. 2, 115-124 (2008). (Pubitemid 351622630)
84. Paramsothy P, Knopp R, Bertoni AG, Tsai MY, Rue T, Heckbert SR: Combined hyperlipidemia in relation to race/ethnicity, obesity, and insulin resistance in the Multi-Ethnic Study of Atherosclerosis (MESA). Metabolism 58, 212-219 (2009).
85. Dobiásová M, Frohlich J: The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FERHDL). Clin. Biochem. 34, 583-588 (2001). (Pubitemid 34014853)
86. Kim-Dorner SJ, Deuster PA, Zeno SA, Remaley AT, Poth M: Should triglycerides and the triglycerides to high-density lipoprotein cholesterol ratio be used as surrogates for insulin resistance? Metabolism 59, 299-304 (2010).
87. Katcher HI, Hill AM, Lanford JL, Yoo JS, Kris-Etherton PM: Lifestyle approaches and dietary strategies to lower LDL-cholesterol and triglycerides and raise HDL-Cholesterol. Endocrinol. Metab. Clin. North Am. 38, 45-78 (2009).
88. Stevens RJ, Kothari V, Adler AI, Stratton IM; United Kingdom Prospective Diabetes Study (UKPDS) Group: The UKPDS Risk Engine: a model for the risk of coronary heart disease in Type 2 diabetes. Clin. Science 101, 671-679 (2001). (Pubitemid 33135349)
89. Assmann G, Cullen P, Schulte H: Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Münster (PROCAM) study. Circulation 105, 310-315 (2002). (Pubitemid 34106178)
90. Kothari V, Stevens RJ, Adler AI et al.: UKPDS 60: risk of stroke in Type 2 diabetes estimated by the UK Prospective Diabetes Study risk engine. Stroke 33, 1776-1781 (2002). (Pubitemid 34761059)
91. Stevens RJ, Coleman RL, Adler AI, Stratton IM, Matthews DR, Holman RR: UKPDS 66: risk factors for myocardial infarction case fatality and stroke case fatality in Type 2 diabetes. Diabetes Care 27, 201-207 (2004). (Pubitemid 38196733)
92. Coleman RL, Stevens RJ, Retnakaran R, Holman RR: Framingham, SCORE and DECODE do not provide reliable cardiovascular risk estimates in Type 2 diabetes. Diabetes Care 30, 1292-1293 (2007).
93. Eichler K, Puhan MA, Steurer J, Bachmann LM: Prediction of first coronary events with the Framingham score: a systematic review. Am. Heart J. 153, 722-731 (2007).
94. Wilson PW: Risk scores for prediction of coronary heart disease: an update. Endocrinol. Metab. Clin. N. Am. 38, 33-44 (2009).
95. Hermans MP, Ahn SA, Rousseau MF: Cardiometabolic phenotype and UKPDS risk in male Type 2 diabetic patients with obstructive sleep apnoea syndrome. Diabetes Metab. Syndr. 3, 50-54 (2009).
96. 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. 37, 925-932 (2007). (Pubitemid 350151189)
97. Carey VJ, Bishop L, Laranjo N, Harschfield BJ, Kwiat C, Sacks FM: Contribution of high plasma triglycerides and low high-density lipoprotein cholesterol to residual risk of coronary heart disease after establishment of low-density lipoprotein cholesterol control. Am. J. Cardiol. 106, 757-763 (2010).
98. Taylor AJ, Villines TC, Stanek E et al.: Extended-release niacin or ezetimibe and carotid intima-media thickness. N. Engl. J. Med. 361, 2113-2122 (2009).
99. Villines TC, Stanek EJ, Devine PJ et al.: The ARBITER 6-HALTS Trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies in Atherosclerosis): final results and the impact of medication adherence, dose, and treatment duration. J. Am. Coll. Cardiol. 55, 2721-2726 (2010).
100. Cushman WC, Grimm RH, Cutler JA; for the ACCORD study group: Rationale and design for the blood pressure intervention of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial. Am. J. Cardiol. 99(12A), 44I-55I (2007).
101. Action to Control Cardiovascular Risk in Diabetes Study Group; Gerstein HC, Miller ME, Byington RP et al.: Effects of intensive glucose lowering in Type 2 diabetes. N. Engl. J. Med. 358, 2545-2559 (2008). (Pubitemid 351831356)
102. ACCORD Study Group; ACCORD Eye Study Group, Chew EY et al.: Effects of medical therapies on retinopathy progression in Type 2 diabetes. N. Engl. J. Med. 363 233-244 (2010).
103. The UKPDS Group: Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with Type 2 diabetes. UKPDS 33. Lancet 837-853 (1998).
104. UK Prospective Diabetes Study Group: Tight blood pressure control and risk of macrovascular and microvascular complications in Type 2 diabetes. UKPDS 38. BMJ 317, 703-713 (1998).
105. Schrier RW, Estacio RO, Esler A et al.: Effects of aggressive blood pressure control in normotensive Type 2 diabetic patients on albuminuria, retinopathy and strokes. Kidney Int. 61, 1086-1097 (2002). (Pubitemid 34175478)
106. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O: Multifactorial intervention and cardiovascular disease in patients with Type 2 diabetes. N. Engl. J. Med. 348, 383-393 (2003). (Pubitemid 36159355)
107. Stratton IM, Cull CA, Adler AI, Matthews DR, Neil HA, Holman RR: Additive effects of glycaemia and blood pressure exposure on risk of complications in Type 2 diabetes: a prospective observational study (UKPDS 75). Diabetologia 49, 1761-1769 (2006). (Pubitemid 44025030)
108. Gaede P, Lund-Andersen H, Parving HH, Pedersen O: Effect of a multifactorial intervention on mortality in Type 2 diabetes. N. Engl. J. Med. 358, 580-591 (2008). (Pubitemid 351214285)
109. Patel A, ADVANCE Collaborative Group; MacMahon S et al.: Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with Type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 370, 829-840 (2007). (Pubitemid 47362321)
110. Fioretto P, Dodson PM, Ziegler D, Rosenson RS: Residual microvascular risk in diabetes: unmet needs and future directions. Nat. Rev. Endocrinol. 6, 19-25 (2010).
111. Dorman TL, Carter RD, Bron AJ, Turner RC, Mann JI: Low density lipoprotein cholesterol: an association with the severity of diabetic retinopathy. Diabetologia 22, 167-170 (1982). (Pubitemid 12183673)
112. Klein BE, Moss SE, Klein R, Surawicz TS: The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XIII. Relationship of serum cholesterol to retinopathy and hard exudate. Ophthalmology 98, 1261-1265 (1991).
113. Chew EY, Klein ML, Ferris FL III et al.: Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Editors Report 22. Arch. Ophthalmol. 114, 1079-1084 (1996).
114. Chowdhury TA, Hopkins D, Dodson PM, Vafidis GC: The role of serum lipids in exudative diabetic maculopathy: is there a place for lipid-lowering therapy? Eye (Lond.) 16, 689-693 (2002). (Pubitemid 35460544)
115. Misra A, Kumar S, Kishore Vikram A, Kumar A: The role of lipids in the development of diabetic microvascular complications: implications for therapy. Am. J. Cardiovasc. Drugs 3, 325-338 (2003). (Pubitemid 37369366)
116. Lyons TJ, Jenkins AJ, Zheng D et al.: Diabetic retinopathy and serum lipoprotein subclasses in the DCCT/EDIC cohort. Invest. Ophthalmol. Vis. Sci. 45, 910-918 (2004). (Pubitemid 38868391)
117. Miljanovic B, Glynn RJ, Nathan DM, Manson JE, Schaumberg DA: A prospective study of serum lipids and risk of diabetic macular edema in Type 1 diabetes. Diabetes 53, 2883-2892 (2004). (Pubitemid 39425914)
118. Ucgun NI, Yildirim Z, Kilĩ N, Gürsel E: The importance of serum lipids in exudative diabetic macular edema in Type 2 diabetic patients. Ann. NY Acad. Sci. 100, 213-217 (2007). (Pubitemid 47092655)
119. 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 366, 1849-1861 (2005).
120. Keech AC, Mitchell P, Summanen PA et al.: Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 370, 1687-1697 (2007). (Pubitemid 350100775)
121. Dodson PM: Medical treatment for diabetic retinopathy: do the FIELD microvascular study results support a role for lipid lowering? Pract. Diab. Int. 25, 76-79 (2008).
122. Scott R, O'Brien R, Fulcher G et al.; Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study Investigators: The effects of fenofibrate treatment on cardiovascular disease risk in 9795 people with Type 2 diabetes and various components of the metabolic syndrome: the FIELD study. Diabetes Care 32, 493-498 (2009).
123. Hermans MP: Impact of fenofibrate on Type 2 diabetes patients with features of the metabolic syndrome: subgroup analysis from FIELD. Curr. Cardiol. Rev. 6, 112-118 (2010).
124. Effect of fenofibrate on progression of coronary-artery disease in Type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet 357, 905-910 (2001).
125. Ansquer JC, Foucher C, Rattier S, Taskinen MR, Steiner G; DAIS Investigators: Fenofibrate reduces progression to microalbuminuria over 3 years in a placebo-controlled study in Type 2 diabetes: results from the Diabetes Atherosclerosis Intervention Study (DAIS). Am. J. Kidney Dis. 45, 485-493 (2005). (Pubitemid 40341327)
126. Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC: Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation 98, 2088-2093 (1998). (Pubitemid 28512236)
127. Fruchart JC: Peroxisome proliferator-activated receptor-a (PPARa): at the crossroads of obesity, diabetes and cardiovascular disease. Atherosclerosis 205, 1-8 (2009).
128. Jun M, Foote C, Lv J et al.: Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 375, 1875-1884 (2010).
129. Volek JS, Fernandez ML, Feinman RD, Phinney SD: Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome. Prog. Lipid Res. 47, 307-318 (2008).
130. Ducobu J, Scheen A, Van Gaal L, Velkeniers B, Hermans M: Belgian Expert opinion: how to reduce the residual risk in atherogenic dyslipidemic patients: place of fibrates. Acta Cardiol. 63, 235-248 (2008). (Pubitemid 351548712)
131. Chapman MJ, Redfern JS, McGovern ME, Giral P: Niacin and fibrates in atherogenic dyslipidemia: pharmacotherapy to reduce cardiovascular risk. Pharmacol. Ther. 126, 314-345 (2010).
132. Rosenson RS, Davidson MH, Pourfarzib R: Underappreciated opportunities for low-density lipoprotein management in patients with cardiometabolic residual risk. Atherosclerosis DOI:10.1016/j. atherosclerosis.2010.03.038 (2010) (Epub ahead of print).
133. Brown BG, McBride R, Boden WE, Probstfield J: AIM HIGH: Niacin plus statin to prevent vascular events www.clinicaltrials.gov/ct2/show/NCT00120 289?term=NCT00120289&rank=1
134. Armitage J, Baigent C, Chen Z, Landray M: HPS2-THRIVE: Treatment of HDL to reduce the incidence of vascular events. www.clinicaltrials.gov/ct2/show/ NCT00461 630?term=NCT00461630&rank=1