期刊论文详细信息
Cardiovascular Diabetology
Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor
Enrique Z Fisman2  Robert Klempfner1  Alexander Tenenbaum2 
[1] Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 69978, Israel;Cardiovascular Diabetology Research Foundation, Holon, 58484, Israel
关键词: Type 2 diabetes;    Triglycerides;    Statins;    Obesity;    Metabolic syndrome;    Insulin resistance;    Hypertriglyceridemia;    Fibrates;    Cholesterol;    Cardiovascular risk;   
Others  :  1118930
DOI  :  10.1186/s12933-014-0159-y
 received in 2014-11-24, accepted in 2014-11-25,  发布年份 2014
PDF
【 摘 要 】

The existence of an independent association between elevated triglyceride (TG) levels, cardiovascular (CV) risk and mortality has been largely controversial. The main difficulty in isolating the effect of hypertriglyceridemia on CV risk is the fact that elevated triglyceride levels are commonly associated with concomitant changes in high density lipoprotein (HDL), low density lipoprotein (LDL) and other lipoproteins. As a result of this problem and in disregard of the real biological role of TG, its significance as a plausible therapeutic target was unfoundedly underestimated for many years. However, taking epidemiological data together, both moderate and severe hypertriglyceridaemia are associated with a substantially increased long term total mortality and CV risk. Plasma TG levels partially reflect the concentration of the triglyceride-carrying lipoproteins (TRL): very low density lipoprotein (VLDL), chylomicrons and their remnants. Furthermore, hypertriglyceridemia commonly leads to reduction in HDL and increase in atherogenic small dense LDL levels. TG may also stimulate atherogenesis by mechanisms, such excessive free fatty acids (FFA) release, production of proinflammatory cytokines, fibrinogen, coagulation factors and impairment of fibrinolysis. Genetic studies strongly support hypertriglyceridemia and high concentrations of TRL as causal risk factors for CV disease. The most common forms of hypertriglyceridemia are related to overweight and sedentary life style, which in turn lead to insulin resistance, metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Intensive lifestyle therapy is the main initial treatment of hypertriglyceridemia. Statins are a cornerstone of the modern lipids-modifying therapy. If the primary goal is to lower TG levels, fibrates (bezafibrate and fenofibrate for monotherapy, and in combination with statin; gemfibrozil only for monotherapy) could be the preferable drugs. Also ezetimibe has mild positive effects in lowering TG. Initial experience with en ezetimibe/fibrates combination seems promising. The recently released IMPROVE-IT Trial is the first to prove that adding a non-statin drug (ezetimibe) to a statin lowers the risk of future CV events. In conclusion, the classical clinical paradigm of lipids-modifying treatment should be changed and high TG should be recognized as an important target for therapy in their own right. Hypertriglyceridemia should be treated.

【 授权许可】

   
2014 Tenenbaum et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150208031625797.pdf 1215KB PDF download
Figure 1. 81KB Image download
【 图 表 】

Figure 1.

【 参考文献 】
  • [1]Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, Goldberg AC, Howard WJ, Jacobson MS, Kris-Etherton PM, Lennie TA, Levi M, Mazzone T, Pennathur S: Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation 2011, 123:2292-2333.
  • [2]Nordestgaard BG, Varbo A: Triglycerides and cardiovascular disease. Lancet 2014, 384:626-635.
  • [3]Criqui MH, Heiss G, Cohn R, Cowan LD, Suchindran CM, Bangdiwala S, Kritchevsky S, Jacobs DR Jr, O’Grady HK, Davis CE: Plasma triglyceride level and mortality from coronary heart disease. N Engl J Med 1993, 328:1220-1225.
  • [4]Laakso M, Lehto S, Penttila I, Pyorala K: Lipids and lipoproteins predicting coronary heart disease mortality and morbidity in patients with non-insulin-dependent diabetes. Circulation 1993, 88:1421-1430.
  • [5]West KM, Ahuja MM, Bennett PH, Czyzyk A, De Acosta OM, Fuller JH, Grab B, Grabauskas V, Jarrett RJ, Kosaka K: The role of circulating glucose and triglyceride concentrations and their interactions with other “risk factors” as determinants of arterial disease in nine diabetic population samples from the WHO multinational study. Diabetes Care 1983, 6:361-369.
  • [6]Fontbonne A, Eschwege E, Cambien F, Richard JL, Ducimetiere P, Thibult N, Warnet JM, Claude JR, Rosselin GE: Hypertriglyceridaemia as a risk factor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes: results from the 11-year follow-up of the Paris Prospective Study. Diabetologia 1989, 32:300-304.
  • [7]Bass KM, Newschaffer CJ, Klag MJ, Bush TL: Plasma lipoprotein levels as predictors of cardiovascular death in women. Arch Intern Med 1993, 153:2209-2216.
  • [8]Austin MA, McKnight B, Edwards KL, Bradley CM, McNeely MJ, Psaty BM, Brunzell JD, Motulsky AG: Cardiovascular disease mortality in familial forms of hypertriglyceridemia: a 20-year prospective study. Circulation 2000, 101:2777-2782.
  • [9]He Y, Lam TH, Li LS, He SF, Liang BQ: Triglyceride and coronary heart disease mortality in a 24-year follow-up study in Xi’an, China. Ann Epidemiol 2004, 14:1-7.
  • [10]Almeda-Valdes P, Cuevas-Ramos D, Mehta R, Muñoz-Hernandez L, Cruz-Bautista I, Perez-Mendez O, Tusie-Luna MT, Gomez-Perez FJ, Pajukanta P, Matikainen N, Taskinen MR, Aguilar-Salinas CA: Factors associated with postprandial lipemia and apolipoprotein A-V levels in individuals with familial combined hyperlipidemia.BMC Endocr Disord 2014, 14:90.
  • [11]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.
  • [12]Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM: Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA 2007, 298:309-316.
  • [13]Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, Wood AM, Lewington S, Sattar N, Packard CJ, Collins R, Thompson SG, Danesh J: Major lipids, apolipoproteins, and risk of vascular disease. JAMA 2009, 302:1993-2000.
  • [14]Schwartz GG, Olsson AG, Szarek M, Sasiela WJ: Relation of characteristics of metabolic syndrome to short-term prognosis and effects of intensive statin therapy after acute coronary syndrome: an analysis of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial. Diabetes Care 2005, 28:2508-2513.
  • [15]Kasai T, Miyauchi K, Kurata T, Ohta H, Okazaki S, Miyazaki T, Kajimoto K, Kubota N, Daida H: Prognostic value of the metabolic syndrome for long-term outcomes in patients undergoing percutaneous coronary intervention. Circ J 2006, 70:1531-1537.
  • [16]Anderson JL, Horne BD, Jones HU, Reyna SP, Carlquist JF, Bair TL, Pearson RR, Lappe DL, Muhlestein JB: Which features of the metabolic syndrome predict the prevalence and clinical outcomes of angiographic coronary artery disease? Cardiology 2004, 101:185-193.
  • [17]Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report Circulation 2002, 106:3143-3421.
  • [18]Heiss G, Tamir I, Davis CE, Tyroler HA, Rifkand BM, Schonfeld G, Jacobs D, Frantz ID Jr: Lipoprotein-cholesterol distributions in selected North American populations: the lipid research clinics program prevalence study. Circulation 1980, 61:302-315.
  • [19]Ford ES, Li C, Zhao G, Pearson WS, Mokdad AH: Hypertriglyceridemia and its pharmacologic treatment among US adults. Arch Intern Med 2009, 169:572-578.
  • [20]Berglund L, Brunzell JD, Goldberg AC, Goldberg IJ, Sacks F, Murad MH, Stalenhoef AF: Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012, 97:2969-2989.
  • [21]Assmann G, Schulte H, von Eckardstein A: Hypertriglyceridemia and elevated lipoprotein(a) are risk factors for major coronary events in middle-aged men. Am J Cardiol 1996, 77:1179-1184.
  • [22]Kasai T, Miyauchi K, Yanagisawa N, Kajimoto K, Kubota N, Ogita M, Tsuboi S, Amano A, Daida H: Mortality risk of triglyceride levels in patients with coronary artery disease. Heart 2013, 99:22-29.
  • [23]Neil HA, Cooper J, Betteridge DJ, Capps N, McDowell IF, Durrington PN, Seed M, Mann JI, Humphries SE: All-cause and cardiovascular mortality in treated patients with severe hypertriglyceridemia: A long-term prospective registry study. Atherosclerosis 2010, 211:618-623.
  • [24]Miselli MA, Nora ED, Passaro A, Tomasi F, Zuliani G: Plasma triglycerides predict ten-years all-cause mortality in outpatients with type 2 diabetes mellitus: a longitudinal observational study.Cardiovasc Diabetol 2014, 13:135.
  • [25]Mora S, Rifai N, Buring JE, Ridker PM: Fasting compared with nonfasting lipids and apolipoproteins for predicting incident cardiovascular events. Circulation 2008, 118:993-1001.
  • [26]Stalenhoef AF, de Graaf J: Association of fasting and nonfasting serum triglycerides with cardiovascular disease and the role of remnant-like lipoproteins and small, dense LDL. Curr Opin Lipidol 2008, 19:355-361.
  • [27]Patsch JR, Miesenbock G, Hopferwieser T, Mu hlberger V, Knapp E, Dunn JK, Gotto AM Jr, Patsch W: Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state. Arterioscler Thromb 1992, 12:1336-1345.
  • [28]Karpe F: Postprandial lipoprotein metabolism and atherosclerosis. J Intern Med 1999, 246:341-355.
  • [29]Eberly LE, Stamler J, Neaton JD: Relation of triglyceride levels, fasting and nonfasting, to fatal and nonfatal coronary heart disease. Arch Intern Med 2003, 163:1077-1083.
  • [30]Durrington PN: Triglycerides are more important in atherosclerosis than epidemiology has suggested. Atherosclerosis 1998, 141(Supp l 1):S57-S62.
  • [31]Deedwania P, Barter P, Carmena R, Fruchart JC, Grundy SM, Haffner S, Kastelein JJ, LaRosa JC, Schachner H, Shepherd J, Waters DD: 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, 368:919-928.
  • [32]Cohn JS, McNamara JR, Cohn SD, Ordovas JM, Schaefer EJ: Plasma apolipoprotein changes in the triglyceride-rich lipoprotein fraction of human subjects fed a fat-rich meal. J Lipid Res 1988, 29:925-936.
  • [33]Karpe F, Bell M, Bjorkegren J, Hamsten A: Quantification of postprandial triglyceride-rich lipoproteins in healthy men by retinyl ester labeling and simultaneous measurement of apolipoproteins B-48 and B-100. Arterioscler Thromb Vasc Biol 1995, 15:199-207.
  • [34]Campos H, Khoo C, Sacks FM: Diurnal and acute patterns of postprandial apolipoprotein B-48 in VLDL, IDL, and LDL from normolipidemic humans. Atherosclerosis 2005, 181:345-351.
  • [35]Nakano T, Tanaka A, Okazaki M, Tokita Y, Nagamine T, Nakajima K: Particle size of apoB-48 carrying lipoproteins in remnant lipoproteins isolated from postprandial plasma. Ann Clin Biochem 2011, 48:57-64.
  • [36]Tabas I, Williams KJ, Boren J: Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation 2007, 116:1832-1844.
  • [37]Kannel WB, Vasan RS: Triglycerides as vascular risk factors: new epidemiologic insights. Curr Opin Cardiol 2009, 24:345-350.
  • [38]Wu L, Parhofer KG: Diabetic dyslipidemia. Metabolism 2014.
  • [39]Adiels M, Boren J, Caslake MJ, Stewart P, Soro A, Westerbacka J, Wennberg B, Olofsson SO, Packard C, Taskinen MR: Overproduction of VLDL1 driven by hyperglycemia is a dominant feature of diabetic dyslipidemia. Arterioscler Thromb Vasc Biol 2005, 25:1697-1703.
  • [40]Guerin M, Le Goff W, Lassel TS, Van Tol A, Steiner G, Chapman MJ: Atherogenic role of elevated CE transfer from HDL to VLDL(1) and dense LDL in type 2 diabetes : impact of the degree of triglyceridemia. Arterioscler Thromb Vasc Biol 2001, 21:282-288.
  • [41]Berneis KK, Krauss RM: Metabolic origins and clinical significance of LDL heterogeneity. J Lipid Res 2002, 43:1363-1379.
  • [42]Donahoo WT, Kosmiski LA, Eckel RH: Drugs causing dyslipoproteinemia. Endocrinol Metab Clin North Am 1998, 27:677-697.
  • [43]Brunzell JD: Clinical practice. Hypertriglyceridemia. N Engl J Med 2007, 357:1009-1017.
  • [44]Brinton EA: Effects of ethanol intake on lipoproteins and atherosclerosis. Curr Opin Lipidol 2010, 21:346-351.
  • [45]Taskinen MR, Nikkilä EA, Välimäki M, Sane T, Kuusi T, Kesäniemi A, Ylikahri R: Alcohol-induced changes in serum lipoproteins and in their metabolism. Am Heart J 1987, 113(2 Pt 2):458-464.
  • [46]Ginsberg HN: New perspectives on atherogenesis: role of abnormal triglyceride-rich lipoprotein metabolism. Circulation 2002, 106:2137-2142.
  • [47]Batal R, Tremblay M, Barrett PH, Jacques H, Fredenrich A, Mamer O, Davignon J, Cohn JS: Plasma kinetics of apoC-III and apoE in normolipidemic and hypertriglyceridemic subjects. J Lipid Res 2000, 41:706-718.
  • [48]Cohn JS, Patterson BW, Uffelman KD, Davignon J, Steiner G: Rate of production of plasma and very-low-density lipoprotein (VLDL) apolipoprotein C-III is strongly related to the concentration and level of production of VLDL triglyceride in male subjects with different body weights and levels of insulin sensitivity. J Clin Endocrinol Metab 2004, 89:3949-3955.
  • [49]Campos H, Moye LA, Glasser SP, Stampfer MJ, Sacks FM: Low density lipoprotein size, pravastatin treatment, and coronary events. JAMA 2001, 286:1468-1474.
  • [50]Zheng C, Khoo C, Ikewaki K, Sacks FM: Rapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractions. J Lipid Res 2007, 48:1190-1203.
  • [51]Ooi EM, Barrett PH, Chan DC, Watts GF: Apolipoprotein C-III: understanding an emerging cardiovascular risk factor. Clin Sci 2008, 114:611-624.
  • [52]Malmstrom R, Packard CJ, Caslake M, Bedford D, Stewart P, Yki-Jarvinen H, Shepherd J, Taskinen MR: Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM. Diabetologia 1997, 40:454-462.
  • [53]Kamagate A, Dong HH: FoxO1 integrates insulin signaling to VLDL production. Cell Cycle 2008, 7:3162-3170.
  • [54]Lee SJ, Moye LA, Campos H, Williams GH, Sacks FM: Hypertriglyceridemia but not diabetes status is associated with VLDL containing apolipoprotein CIII in patients with coronary heart disease. Atherosclerosis 2003, 167:293-302.
  • [55]Cheal KL, Abbasi F, Lamendola C, McLaughlin T, Reaven GM, Ford ES: Relationship to insulin resistance of the adult treatment panel III diagnostic criteria for identification of the metabolic syndrome. Diabetes 2004, 53:1195-1200.
  • [56]Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F: Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung and Blood Institute scientific statement. Circulation 2005, 112:2735-2752.
  • [57]Won KB, Chang HJ, Kim HC, Jeon K, Lee H, Shin S, Cho IJ, Park SH, Lee SH, Jang Y: Differential impact of metabolic syndrome on subclinical atherosclerosis according to the presence of diabetes.Cardiovasc Diabetol 2013, 12:41.
  • [58]Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr: 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 2009, 120:1640-1645.
  • [59]An X, Yu D, Zhang R, Zhu J, Du R, Shi Y, Xiong X: Insulin resistance predicts progression of de novo atherosclerotic plaques in patients with coronary heart disease: a one-year follow-up study.Cardiovasc Diabetol 2012, 11:71.
  • [60]Nieves DJ, Cnop M, Retzlaff B, Walden CE, Brunzell JD, Knopp RH, Kahn SE: The atherogenic lipoprotein profile associated with obesity and insulin resistance is largely attributable to intraabdominal fat. Diabetes 2003, 52:172-179.
  • [61]Novo S, Peritore A, Trovato RL, Guarneri FP, Di Lisi D, Muratori I, Novo G: Preclinical atherosclerosis and metabolic syndrome increase cardio- and cerebrovascular events rate: a 20-year follow up.Cardiovasc Diabetol 2013, 12:155.
  • [62]Feinberg MS, Schwartz R, Tanne D, Fisman EZ, Hod H, Zahger D, Schwammenthal E, Eldar M, Behar S, Tenenbaum A: Impact of the metabolic syndrome on the clinical outcomes of non-clinically diagnosed diabetic patients with acute coronary syndrome. Am J Cardiol 2007, 99:667-672.
  • [63]Brunzell JD, Ayyobi AF: Dyslipidemia in the metabolic syndrome and type 2 diabetes mellitus. Am J Med 2003, 115(Suppl 8A):24S-28S.
  • [64]Herder M, Arntzen KA, Johnsen SH, Mathiesen EB: The metabolic syndrome and progression of carotid atherosclerosis over 13 years. The Tromsø study.Cardiovasc Diabetol 2012, 11:77.
  • [65]Pilz S, Scharnagl H, Tiran B, Seelhorst U, Wellnitz B, Boehm BO, Schaefer JR, Marz W: Free fatty acids are independently associated with all-cause and cardiovascular mortality in subjects with coronary artery disease. J Clin Endocrinol Metab 2006, 91:2542-2547.
  • [66]Oliver MF: Prevention of ventricular fibrillation during acute myocardial ischemia: control of free fatty acids. J Cardiovasc Pharmacol Ther 2001, 6:213-217.
  • [67]Tripathy D, Mohanty P, Dhindsa S, Syed T, Ghanim H, Aljada A, Dandona P: Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects. Diabetes 2003, 52:2882-2887.
  • [68]Lee JY, Sohn KH, Rhee SH, Hwang D: Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J Biol Chem 2001, 276:16683-16689.
  • [69]Itoh Y, Kawamata Y, Harada M, Kobayashi M, Fujii R, Fukusumi S, Ogi K, Hosoya M, Tanaka Y, Uejima H, Tanaka H, Maruyama M, Satoh R, Okubo S, Kizawa H, Komatsu H, Matsumura F, Noguchi Y, Shinohara T, Hinuma S, Fujisawa Y, Fujino M: Free fatty acids regulate insulin secretion from pancreatic cells through GPR40. Nature 2003, 422:173-176.
  • [70]Briscoe CP, Tadayyon M, Andrews JL, Benson WG, Chambers JK, Eilert MM, Ellis C, Elshourbagy NA, Goetz AS, Minnick DT, Murdock PR, Sauls HR Jr, Shabon U, Spinage LD, Strum JC, Szekeres PG, Tan KB, Way JM, Ignar DM, Wilson S, Muir AI: The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids. J Biol Chem 2003, 278:11303-11311.
  • [71]Hirasawa A, Tsumaya K, Awaji T, Katsuma S, Adachi T, Yamada M, Sugimoto Y, Miyazaki S, Tsujimoto G: Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med 2005, 11:90-94.
  • [72]Mathew M, Tay E, Cusi K: Elevated plasma free fatty acids increase cardiovascular risk by inducing plasma biomarkers of endothelial activation, myeloperoxidase and PAI-1 in healthy subjects.Cardiovasc Diabetol 2010, 9:9.
  • [73]Boden G, Lebed B, Schatz M, Homko C, Lemieux S: Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance in healthy subjects. Diabetes 2001, 50:1612-1617.
  • [74]Itani SI, Ruderman NB, Schmieder F, Boden G: Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IκB-α. Diabetes 2002, 51:2005-2011.
  • [75]Barazzoni R, Zanetti M, Gortan Cappellari G, Semolic A, Boschelle M, Codarin E, Pirulli A, Cattin L, Guarnieri G: Fatty acids acutely enhance insulin-induced oxidative stress and cause insulin resistance by increasing mitochondrial reactive oxygen species (ROS) generation and nuclear factor-κB inhibitor (IκB)-nuclear factor-κB (NFκB) activation in rat muscle, in the absence of mitochondrial dysfunction. Diabetologia 2012, 55:773-782.
  • [76]Boden G, She P, Mozzoli M, Cheung P, Gumireddy K, Reddy P, Xiang X, Luo Z, Ruderman N: Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-κB pathway in rat liver. Diabetes 2005, 54:3458-3465.
  • [77]Hotamisligil GS: Role of endoplasmic reticulum stress and c-Jun NH2-terminal kinase pathways in inflammation and origin of obesity and diabetes. Diabetes 2005, 54:S73-S78.
  • [78]Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, Sano H, Utsumi H, Nawata H: High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 2000, 49:1939-1945.
  • [79]Shi A, Kokoeva V, Inouye K, Tzameli I, Yin H, Flier JS: TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 2006, 116:3015-3025.
  • [80]Yu C, Chen Y, Cline GW, Zhang D, Zong H, Wang Y, Bergeron R, Kim JK, Cushman SW, Cooney GJ, Atcheson B, White MF, Kraegen EW, Shulman GI: Mechanism by which fatty acids inhibit activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem 2002, 277:50230-50236.
  • [81]Saltiel AR, Kahn CR: Insulin signaling and the regulation of glucose and lipid metabolism. Nature 2001, 414:799-806.
  • [82]Newby AC: Dual role of matrix metalloproteinases (Matrixins) in intimal thickening of atherosclerotic plaque rupture. Physiol Rev 2005, 85:1-31.
  • [83]Galis ZS, Sukhova GK, Lark MW, Libby P: Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 1994, 94:2493-2503.
  • [84]Pasterkamp G, Schoneveld AH, Hijnen DJ, e Kleijn DP, Teepen H, van der Wal AC, Borst C: Atherosclerotic arterial remodeling and the localization of macrophages and matrix metalloproteinases 1, 2 and 9 in the human coronary artery. Atherosclerosis 2000, 150:245-253.
  • [85]Longo GM, Xiong W, Greiner TC, Zhao Y, Fiotti N, Baxter BT: Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. J Clin Invest 2002, 110:625-632.
  • [86]Long SD, Pekala PH: Regulation of Glut4 gene expression by arachidonic acid. Evidence for multiple pathways, one of which requires oxidation to prostaglandin. J Biol Chem 1996, 271:1138-1144.
  • [87]Armoni M, Harel C, Bar-Yoseph F, Milo S, Karnieli E: Free fatty acids repress the Glut4 gene expression in cardiac muscle via novel response elements. J Biol Chem 2005, 280:34786-34795l.
  • [88]Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H: Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003, 112:1821-1830.
  • [89]van Oostrom AJ, van Dijk H, Verseyden C, Sniderman AD, Cianflone K, Rabelink TJ, Castro Cabezas M: Addition of glucose to an oral fat load reduces postprandial free fatty acids and prevents the postprandial increase in complement component 3. Am J Clin Nutr 2004, 79:5-10.
  • [90]Rollins BJ, Walz A, Baggiolini M: Recombinant human MCP-1/JE induces chemotaxis, calcium flux, and the respiratory burst in human monocytes. Blood 1991, 78:1112-1116.
  • [91]Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr: Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003, 112:1796-1808.
  • [92]Gao Z, Zhang X, Zuberi A, Hwang D, Quon MJ, Lefevre M, Ye J: Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3T3-L1 adipocytes. Mol Endocrinol 2004, 18:2024-2034.
  • [93]Medzhitov R: Toll-like receptors and innate immunity. Nat Rev Immunol 2001, 1:135-145.
  • [94]Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Görgün C, Glimcher LH, Hotamisligil GS: Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 2004, 306:457-461.
  • [95]Tomita T, Hosoda K, Fujikura J, Inagaki N, Nakao K: The G-protein-coupled long-chain fatty acid receptor GPR40 and glucose metabolism.Front Endocrinol (Lausanne) 2014, 5:152.
  • [96]Boden G: Free fatty acids and insulin secretion in humans. Curr Diab Rep 2005, 5:167-270.
  • [97]Benjamin SM, Valdez R, Geiss LS, Rolka DB, Narayan KM: Estimated number of adults with prediabetes in the US in 2000: opportunities for prevention. Diabetes Care 2003, 26:645-649.
  • [98]Bamba V, Rader DJ: Obesity and atherogenic dyslipidemia. Gastroenterology 2007, 132:2181-2190.
  • [99]Boden G, Rao AK: Effects of hyperglycemia and hyperinsulinemia on the tissue factor pathway of blood coagulation. Curr Diab Rep 2007, 7:223-227.
  • [100]Boden G, Vaidyula VR, Homko C, Cheung P, Rao AK: Circulating tissue factor procoagulant activity and thrombin generation in patients with type 2 diabetes: Effects of insulin and glucose. J Clin Endocrinol Metab 2007, 92:4352-4358.
  • [101]Vague P, Juhan-Vague I, Aillaud MF, Badier C, Viard R, Alessi MC, Collen D: Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level and relative body weight in normal and obese subjects. Metabolism 1986, 35:250-253.
  • [102]Pannacciulli N, De Mitrio R, Giorgino R, De Pergola G: Effect of glucose tolerance status on PAI-1 plasma levels in overweight and obese subjects. Obes Res 2002, 10:717-725.
  • [103]Festa A, D’Agostino R Jr, Tracy RP, Haffner SM: Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the Insulin Resistance Atherosclerosis Study. Diabetes 2002, 51:1131-1137.
  • [104]Sobel BE, Schneider DJ: Platelet function, coagulopathy, and impaired fibrinolysis in diabetes. Cardiol Clin 2004, 22:511-526.
  • [105]Hennekens CH: Increasing burden of cardiovascular disease: current knowledge and future directions for research on risk factors. Circulation 1998, 97:1095-1102.
  • [106]Shimabukuro M, Zhou YT, Levi M, Unger RH: Fatty acid-induced beta cell apoptosis: a link between obesity and diabetes. Proc Natl Acad Sci U S A 1998, 95:2498-2502.
  • [107]Unger RH: Lipotoxicity in the pathogenesis of obesity-dependent NIDDM Genetic and clinical implications. Diabetes 1995, 44:863-870.
  • [108]Robertson RP, Harmon J, Tran PO, Poitout V: Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes 2004, 53(Suppl 1):S119-S124.
  • [109]Haber EP, Procopio J, Carvalho CR, Carpinelli AR, Newsholme P, Curi R: New insights into fatty acid modulation of pancreatic beta-cell function. Int Rev Cytol 2006, 248:1-41.
  • [110]Pick A, Clark J, Kubstrup C, Levisetti M, Pugh W, Bonner-Weir S, Polonsky KS: Role of apoptosis in failure of beta cell mass compensation for insulin resistance and beta cell defects in the male Zucker diabetic fatty rat. Diabetes 1998, 47:358-364.
  • [111]Zhou YT, Shimabukuro M, Wang MY, Lee Y, Higa M, Milburn JL, Newgard CB, Unger RH: Role of peroxisome proliferator-activated receptor alpha in disease of pancreatic beta cells. Proc Natl Acad Sci U S A 1998, 95:8898-8903.
  • [112]Arner P: Free fatty acids - do they play a central role in type 2 diabetes? Diab Obes Metab 2001, 3(Suppl 1):11-19.
  • [113]Tenenbaum H, Behar S, Boyko V, Adler Y, Fisman EZ, Tanne D, Lapidot M, Schwammenthal E, Feinberg M, Matas Z, Motro M, Tenenbaum A: Long-term effect of bezafibrate on pancreatic beta-cell function and insulin resistance in patients with diabetes. Atherosclerosis 2007, 194:265-271.
  • [114]Shafrir E, Raz I: Diabetes: mellitus or lipidus? Diabetologia 2003, 46:433-440.
  • [115]Badimon JJ, Badimon L, Fuster V: Regression of atherosclerotic lesions by high density lipoprotein plasma fraction in the cholesterol-fed rabbit. J Clin Invest 1990, 85:1234-1243.
  • [116]Rubin E, Krauss R, Spangler E, Verstuyft J, Clift S: Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI. Nature 1991, 353:265-267.
  • [117]Tangirala RK, Tsukamoto K, Chun SH, Usher D, Pure E, Rader DJ: Regression of atherosclerosis induced by liver-directed gene transfer of apolipoprotein A-I in mice. Circulation 1999, 100:1816-1822.
  • [118]Castelli WP, Garrison RJ, Wilson PW, Abbott RD, Kalousdian S, Kannel WB: Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA 1986, 256:2835-2838.
  • [119]Assmann G, Schulte H, von Eckardstein A, Huang Y: High density lipoprotein cholesterol as a predictor of coronary heart disease risk. The PROCAM experience and pathophysiological implications for reverse cholesterol transport. Atherosclerosis 1996, 124(Suppl):S11-S20.
  • [120]von Eckardstein A, Nofer JR, Assmann G: High density lipoproteins and arteriosclerosis. Role of cholesterol efflux and reverse cholesterol transport. Arterioscler Thromb Vasc Biol 2001, 21:13-27.
  • [121]Leança CC, Nunes VS, Panzoldo NB, Zago VS, Parra ES, Cazita PM, Jauhiainen M, Passarelli M, Nakandakare ER, de Faria EC, Quintão EC: Metabolism of plasma cholesterol and lipoprotein parameters are related to a higher degree of insulin sensitivity in high HDL-C healthy normal weight subjects.Cardiovasc Diabetol 2013, 12:173.
  • [122]Annema W, von Eckardstein A: High-density lipoproteins. Multifunctional but vulnerable protections from atherosclerosis. Circ J 2013, 77:2432-2448.
  • [123]Tong X, Peng H, Liu D, Ji L, Niu C, Ren J, Pan B, Hu J, Zheng L, Huang Y: High-density lipoprotein of patients with type 2 diabetes mellitus upregulates cyclooxgenase-2 expression and prostacyclin I-2 release in endothelial cells: relationship with HDL-associated sphingosine-1-phosphate.Cardiovasc Diabetol 2013, 12:27.
  • [124]Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, Lopez-Sendon J, Mosca L, Tardif JC, Waters DD, Shear CL, Revkin JH, Buhr KA, Fisher MR, Tall AR, Brewer B: Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007, 357:2109-2122.
  • [125]Funder JW: Aldosterone, sodium, and hypertension: lessons from torcetrapib? Hypertension 2010, 55:221-223.
  • [126]Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, Chaitman BR, Holme IM, Kallend D, Leiter LA, Leitersdorf E, McMurray JJ, Mundl H, Nicholls SJ, Shah PK, Tardif JC, Wright RS: Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med 2012, 367:2089-2099.
  • [127]Investigators AIM-HIGH, Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, McBride R, Teo K, Weintraub W: Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011, 365:2255-2267.
  • [128]Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, Tomson J, Wallendszus K, Craig M, Jiang L, Collins R, Armitage J: Effects of extended release niacin with laropiprant in high-risk patients. N Engl J Med 2014, 371:203-212.
  • [129]Rader DJ, Tall AR: The not-so-simple HDL story: is it time to revise the HDL cholesterol hypothesis? Nat Med 2012, 18:1344-1346.
  • [130]Rader DJ, Hovingh GK: HDL and cardiovascular disease. Lancet 2014, 384:618-625.
  • [131]Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, Pirruccello JP, Ripatti S, Chasman DI, Willer CJ, Johansen CT, Fouchier SW, Isaacs A, Peloso GM, Barbalic M, Ricketts SL, Bis JC, Aulchenko YS, Thorleifsson G, Feitosa MF, Chambers J, Orho-Melander M, Melander O, Johnson T, Li X, Guo X, Li M, Shin Cho Y, Jin Go M, Jin Kim Y, et al.: Biological, clinical and population relevance of 95 loci for blood lipids. Nature 2010, 466:707-713.
  • [132]Do R, Willer CJ, Schmidt EM, Sengupta S, Gao C, Peloso GM, Gustafsson S, Kanoni S, Ganna A, Chen J, Buchkovich ML, Mora S, Beckmann JS, Bragg-Gresham JL, Chang HY, Demirkan A, Den Hertog HM, Donnelly LA, Ehret GB, Esko T, Feitosa MF, Ferreira T, Fischer K, Fontanillas P, Fraser RM, Freitag DF, Gurdasani D, Heikkilä K, Hyppönen E, Isaacs A: Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet 2013, 45:1345-1352.
  • [133]Varbo A, Benn M, Tybjaerg-Hansen A, Jorgensen AB, Frikke-Schmidt R, Nordestgaard BG: Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol 2013, 61:427-436.
  • [134]Thomsen M, Varbo A, Tybjærg-Hansen A, Nordestgaard BG: Low nonfasting triglycerides and reduced all-cause mortality: a mendelian randomization study. Clin Chem 2014, 60:737-746.
  • [135]Calabresi L, Simonelli S, Gomaraschi M, Franceschini G: Genetic lecithin:cholesterol acyltransferase defi ciency and cardiovascular disease. Atherosclerosis 2012, 222:299-306.
  • [136]de Grooth GJ, Klerkx AH, Stroes ES, Stalenhoef AF, Kastelein JJ, Kuivenhoven JA: A review of CETP and its relation to atherosclerosis. J Lipid Res 2004, 45:1967-1974.
  • [137]Adams JN, Cox AJ, Freedman BI, Langefeld CD, Carr JJ, Bowden DW: Genetic analysis of haptoglobin polymorphisms with cardiovascular disease and type 2 diabetes in the Diabetes Heart Study.Cardiovasc Diabetol 2013, 12:31.
  • [138]Sarwar N, Sandhu MS, Ricketts SL, Butterworth AS, Di Angelantonio E, Boekholdt SM, Ouwehand W, Watkins H, Samani NJ, Saleheen D, Lawlor D, Reilly MP, Hingorani AD, Talmud PJ, Danesh J: Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet 2010, 375:1634-1639.
  • [139]Chapman MJ, Ginsberg HN, Amarenco P, Andreotti F, Borén J, Catapano AL, Descamps OS, Fisher E, Kovanen PT, Kuivenhoven JA, Lesnik P, Masana L, Nordestgaard BG, Ray KK, Reiner Z, Taskinen MR, Tokgözoglu L, Tybjærg-Hansen A, Watts GF: 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, 32:1345-1361.
  • [140]Hegele RA, Ginsberg HN, Chapman MJ, Nordestgaard BG, Kuivenhoven JA, Averna M, Borén J, Bruckert E, Catapano AL, Descamps OS, Hovingh GK, Humphries SE, Kovanen PT, Masana L, Pajukanta P, Parhofer KG, Raal FJ, Ray KK, Santos RD, Stalenhoef AF, Stroes E, Taskinen MR, Tybjærg-Hansen A, Watts GF, Wiklund O: The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diab Endocrinol 2014, 2:655-666.
  • [141]Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, Agewall S, Alegria E, Chapman MJ, Durrington P, Erdine S, Halcox J, Hobbs R, Kjekshus J, Filardi PP, Riccardi G, Storey RF, Wood D: 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). Eur Heart J 2011, 32:1769-1818.
  • [142]Ray K: Statin diabetogenicity: guidance for clinicians.Cardiovasc Diabetol 2013, 12(Suppl 1):S3.
  • [143]Mita T, Nakayama S, Abe H, Gosho M, Iida H, Hirose T, Kawamori R, Watada H: Comparison of effects of pitavastatin and atorvastatin on glucose metabolism in type 2 diabetic patients with hypercholesterolemia. J Diabetes Investig 2013, 4:297-303.
  • [144]Ginsberg H: Statins in cardiometabolic disease: what makes pitavastatin different?Cardiovasc Diabetol 2013, 12(Suppl 1):S1.
  • [145]Chapman MJ, Orsoni A, Robillard P, Hounslow N, Sponseller CA, Giral P: Effect of high-dose pitavastatin on glucose homeostasis in patients at elevated risk of new-onset diabetes: insights from the CAPITAIN and PREVAIL-US studies. Curr Med Res Opin 2014, 30:775-784.
  • [146]Masana L: Pitavastatin in cardiometabolic disease: therapeutic profile.Cardiovasc Diabetol 2013, 12(Suppl 1):S2.
  • [147]Saravanan P, Davidson NC, Schmidt EB, Calder PC: Cardiovascular effects of marine omega-3 fatty acids. Lancet 2010, 376:540-550.
  • [148]Swanson D, Block R, Mousa SA: Omega-3 fatty acids EPA and DHA: health benefits throughout life. Adv Nutr 2012, 3:1-7.
  • [149]Brinton EA, Ballantyne CM, Bays HE, Kastelein JJ, Braeckman RA, Soni PN: Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study.Cardiovasc Diabetol 2013, 12:100.
  • [150]Bosch J, Gerstein HC, Dagenais GR, Díaz R, Dyal L, Jung H, Maggiono AP, Probstfield J, Ramachandran A, Riddle MC, Rydén LE, Yusuf S: n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med 2012, 367:309-318.
  • [151]Roncaglioni MC, Tombesi M, Avanzini F, Barlera S, Caimi V, Longoni P, Marzona I, Milani V, Silletta MG, Tognoni G, Marchioli R: n-3 fatty acids in patients with multiple cardiovascular risk factors. N Engl J Med 2013, 368:1800-1808.
  • [152]Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS: Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA 2012, 308:1024-1033.
  • [153]Pandor A, Ara RM, Tumur I, Wilkinson AJ, Paisley S, Duenas A, Durrington PN, Chilcott J: Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials. J Intern Med 2009, 265:568-580.
  • [154]Bozzetto L, Annuzzi G, Corte GD, Patti L, Cipriano P, Mangione A, Riccardi G, Rivellese AA: Ezetimibe beneficially influences fasting and postprandial triglyceride-rich lipoproteins in type 2 diabetes. Atherosclerosis 2011, 217:142-148.
  • [155]Teramoto T, Abe K, Taneyama T: Safety and efficacy of long-term combination therapy with bezafibrate and ezetimibe in patients with dyslipidemia in the prospective, observational J-COMPATIBLE study.Cardiovasc Diabetol 2013, 12:163.
  • [156]Farnier M, Retterstøl K, Steinmetz A, Császár A: Comparative efficacy and safety of fenofibrate/pravastatin plus ezetimibe triple therapy and simvastatin/ezetimibe dual therapy in type 2 diabetic patients with mixed hyperlipidaemia and cardiovascular disease. Diab Vasc Dis Res 2012, 9:205-215.
  • [157][http:/ / newsroom.heart.org/ news/ cholesterol-lowering-drug-with-diff erent-action-adds-to-statins-reduct ion-of-cardiovascular-risk] webcite Cannon CP (presenter): Cholesterol-lowering drug with different action adds to statin’s reduction of cardiovascular risk. American Heart Association Meeting Report Abstract LBCT.02. (accessed 21/11/2014).
  • [158]Knopp RH: Drug treatment of lipid disorders. N Engl J Med 1999, 341:498-511.
  • [159]Tenenbaum A, Fisman EZ, Motro M, Adler Y: Optimal management of combined dyslipidemia: what have we behind statins monotherapy? Adv Cardiol 2008, 45:127-153.
  • [160]Tenenbaum A, Fisman EZ, Boyko V, Benderly M, Tanne D, Haim M, Matas Z, Motro M, Behar S: Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate. Arch Intern Med 2006, 166:737-741.
  • [161]Teramoto T, Shirai K, Daida H, Yamada N: Effects of bezafibrate on lipid and glucose metabolism in dyslipidemic patients with diabetes: the J-BENEFIT study.Cardiovasc Diabetol 2012, 11:29.
  • [162]Tenenbaum A, Motro M, Fisman EZ, Tanne D, Boyko V, Behar S: Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome. Arch Intern Med 2005, 165:1154-1160.
  • [163]Effects of combination lipid therapy in type 2 diabetes mellitus N Engl J Med 2010, 362:1563-1574.
  • [164]Tenenbaum A, Fisman EZ: “If it ain”t broke, don’t fix it”: a commentary on the positive–negative results of the ACCORD Lipid study.Cardiovasc Diabetol 2010, 9:24.
  • [165]Scott R, O’Brien R, Fulcher G, Pardy C, D’Emden M, Tse D, Taskinen MR, Ehnholm C, Keech A: Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetes Care 2009, 32:493-498.
  • [166]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.
  • [167]Manninen V, Tenkanen L, Koskinen P, Huttunen JK, Mänttäri M, Heinonen OP, Frick MH: 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.
  • [168]Robins SJ, Collins D, Wittes JT, Papademetriou V, Deedwania PC, Schaefer EJ, McNamara JR, Kashyap ML, Hershman JM, Wexler LF, Rubins HB: Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. JAMA 2001, 285:1585-1591.
  • [169]Sacks FM, Carey VJ, Fruchart JC: Combination lipid therapy in type 2 diabetes. N Engl J Med 2010, 363:692-694.
  • [170]Jun M, Foote C, Lv J, Neal B, Patel A, Nicholls SJ, Grobbee DE, Cass A, Chalmers J, Perkovic V: Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 2010, 375:1875-1878.
  • [171]Tenenbaum A, Medvedofsky D, Fisman EZ, Bubyr L, Matetzky S, Tanne D, Klempfner R, Shemesh J, Goldenberg I: Cardiovascular events in patients received combined fibrate/statin treatment versus statin monotherapy: Acute Coronary Syndrome Israeli Surveys data.PLoS One 2012, 7(4):e35298.
  • [172]Klempfner R, Goldenberg I, Fisman EZ, Matetzky S, Amit U, Shemesh J, Tenenbaum A: Comparison of statin alone versus bezafibrate and statin combination in patients with diabetes mellitus and acute coronary syndrome. Am J Cardiol 2014, 113:12-16.
  • [173]Tenenbaum A, Fisman EZ: Balanced pan-PPAR activator bezafibrate in combination with statin: comprehensive lipids control and diabetes prevention?Cardiovasc Diabetol 2012, 11:140.
  • [174]Tenenbaum A, Fisman EZ: Fibrates are an essential part of modern anti-dyslipidemic arsenal: spotlight on atherogenic dyslipidemia and residual risk reduction.Cardiovasc Diabetol 2012, 11:125.
  文献评价指标  
  下载次数:1次 浏览次数:6次