Adipositas - Ursachen, Folgeerkrankungen, Therapie 2009; 03(03): 123-127
DOI: 10.1055/s-0037-1618678
Adipositas und Lipidstoffwechselstörungen
Schattauer GmbH

Postprandialer Lipoproteinstoffwechsel und kardiovaskuläres Risiko

Postprandial lipid metabolism and cardiovascular risk
M. Merkel
1   Medizinische Abteilung (Diabetes, Stoffwechsel, Endokrinologie, Gastroenterologie und Allgemeine Innere Medizin), Asklepios Klinik St. Georg, Hamburg; Institute for Diabetes Research, Lipide und Diabetes (LiDia)
› Author Affiliations
Further Information

Publication History

Publication Date:
22 December 2017 (online)

Zusammenfassung

Erhöhte Plasma-Triglyzeridspiegel sind mit kardiovaskulären Erkrankungen assoziiert. Das Ausmaß dieses Effekts und der molekulare Mechanismus der Atherogenität der Triglyzeride sind jedoch unklar. Es wird angenommen, dass die triglyzeridreichen Lipoproteine selbst nicht atherogen sind, sondern ihre metabolischen Folgen, Restpartikel (Chylomikronen-und VLDL-Remnants), kleine dichte LDL (sdLDL) und erniedrigtes HDL-Cholesterin. In prospektiven Studien wurde gezeigt, dass beim Vergleich der höchsten mit den niedrigsten Subgruppen die Nüchtern-Triglyzeride das adjustierte kardiovaskuläre Risiko (hazard ratio) auf 1,7, und postprandiale Triglyzeride sogar auf bis zu 5 erhöhen können. Neben Gesamtcholesterin, Triglyzeriden, LDL-und HDLCholesterin wäre die Bestimmung postprandialer Triglyzeridwerte durchaus sinnvoll; hierfür existiert aber keine anerkannte standardisierte Methode. In der klinischen Routine kann eine Berechnung des Non-HDL-Cholesterins und in Zukunft möglicherweise auch die Messung des Apolipoprotein-B-Plasmaspiegels eine bessere Einschätzung der Atherogenität des Lipidprofils bei erhöhten Triglyzeriden bieten.

Summary

Elevated serum triglyceride levels are associated with cardiovascular disease. The extent of the triglyceride contribution to the cardiovascular risk and the mechanisms by which triglyceride-rich lipoproteins exert their atherogenicity on the vascular wall are mostly unknown. Most likely, not triglyceride rich particles themselves but cholesterol-rich remnant particles, small dense LDL and decreased HDL cholesterol mediate these effects. Prospective studies have shown that fasting triglyceride levels can increase the adjusted hazard ratios for cardiovascular disease risk up to 1.7, and nonfasting levels in some populations up to 5, comparing highest with lowest subgroups. Besides total cholesterol, triglycerides, LDL and HDL cholesterol, estimation of nonfasting triglycerides may be useful, but there is no widely accepted standardized protocol for a postprandial test. For clinical practice, non-HDL cholesterol and the plasma concentration of apolipoprotein B may reflect the atherogenic lipoprotein subfractions in hypertriglyceridemia best.

 
  • Literatur

  • 1 Austin MA, King MC, Vranizan KM. et al. Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk. Circulation 1990; 82 (02) 495-506.
  • 2 Carlson L, Böttiger L. Ischaemic heart-disease in relation to fasting values of plasma triglycerides and cholesterol. Stockholm prospective study. Lancet 1972; 01 7756 865-868.
  • 3 Duez H, Lamarche B, Uffelman KD. et al. Hyperinsulinemia is associated with increased production rate of intestinal apolipoprotein B-48-containing lipoproteins in humans. Arterioscler Thromb Vasc Biol 2006; 26 (06) 1357-1363.
  • 4 Hsieh J, Hayashi AA, Webb J. et al. Postprandial dyslipidemia in insulin resistance: mechanisms and role of intestinal insulin sensitivity. Atheroscler Suppl 2008; 09 (02) 7-13.
  • 5 Taskinen MR. Pathogenesis of dyslipidemia in type 2 diabetes. Exp Clin Endocrinol Diabetes 2001; 109 (Suppl. 02) S180-S188.
  • 6 Ginsberg HN, Zhang YL, Hernandez-Ono A. Regulation of plasma triglycerides in insulin resistance and diabetes. Arch Med Res 2005; 36 (03) 232-240.
  • 7 Brunzell JD, Deeb S. Familial lipoprotein lipase deficiency, apo CII deficiency, and hepatic lipase deficiency. In: Scriver CR, Beaudet AL, Valle D, Sly WS. The Metabolic and Molecular Bases of Inherited Disease. 8th. ed. New York: McGraw-Hill; 2001: 2789-2816.
  • 8 Talmud PJ, Hawe E, Martin S. et al. Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycerides. Hum Mol Genet 2002; 11 (24) 3039-3046 #
  • 9 Talmud PJ, Smart M, Presswood E. et al. ANGPTL4 E40K and T266M: effects on plasma triglyceride and HDL levels, postprandial responses, and CHD risk. Arterioscler Thromb Vasc Biol 2008; 28 (12) 2319-2325.
  • 10 Merkel M. Diabetische Dyslipoproteinemie: Jenseits von LDL. Dtsch Med Wochenschr 2009; 134 (20) 1067-1073.
  • 11 Beigneux AP, Franssen R, Bensadoun A. et al. Chylomicronemia with a mutant GPIHBP1 (Q115P) that cannot bind lipoprotein lipase. Arterioscler Thromb Vasc Biol 2009; 29 (06) 956-962.
  • 12 Utermann G, Hees M, Steinmetz A. Polymorphism of apolipoprotein E and occurrence of dysbetalipoproteinaemia in man. Nature 1977; 269 (5629): 604-607.
  • 13 Laatsch A, Merkel M, Talmud PJ. et al. Insulin stimulates hepatic low density lipoprotein receptor-related protein 1 (LRP1) to increase postprandial lipoprotein clearance. Atherosclerosis 2009; 204 (01) 105-111.
  • 14 Karpe F, Bickerton AS, Hodson L. et al. Removal of triacylglycerols from chylomicrons and-VLDL by capillary beds: the basis of lipoprotein remnant formation. Biochem Soc Trans 2007; 35 (Pt 3): 472-476.
  • 15 Nordestgaard BG, Benn M, Schnohr P. et al. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. Jama 2007; 298 (03) 299-308.
  • 16 McNamara JR, Shah PK, Nakajima K. et al. Remnant-like particle (RLP) cholesterol is an independent cardiovascular disease risk factor in women: results from the Framingham Heart Study. Atherosclerosis 2001; 154 (01) 229-236.
  • 17 Patsch JR, Miesenbock G, Hopferwieser T. et al. Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state. Arterioscler Thromb 1992; 12 (11) 1336-1345.
  • 18 Gardner CD, Fortmann SP, Krauss RM. Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. Jama 1996; 276 (11) 875-881.
  • 19 Lamarche B, Tchernof A, Moorjani S. et al. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study. Circulation 1997; 95 (01) 69-75.
  • 20 Gordon T, Castelli WP, Hjortland MC. et al. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 1977; 62 (05) 707-714.
  • 21 Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996; 03 (02) 213-219.
  • 22 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 (04) 450-458.
  • 23 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) 2008; 32 (Suppl. 02) S11-S16.
  • 24 Tirosh A, Rudich A, Shochat T. et al. Changes in triglyceride levels and risk for coronary heart disease in young men. Ann Intern Med 2007; 147 (06) 377-385.
  • 25 Zilversmit DB. Atherogenesis: a postprandial phenomenon. Circulation 1979; 60 (03) 473-485.
  • 26 Patel A, Barzi F, Jamrozik K. et al. Serum triglycerides as a risk factor for cardiovascular diseases in the Asia-Pacific region. Circulation 2004; 110 (17) 2678-2686.
  • 27 Freiberg JJ, Tybjaerg-Hansen A, Jensen JS. et al. Nonfasting triglycerides and risk of ischemic stroke in the general population. Jama 2008; 300 (18) 2142-2152.
  • 28 Bansal S, Buring JE, Rifai N. et al. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. Jama 2007; 298 (03) 309-316.
  • 29 Mora S, Rifai N, Buring JE. et al. Fasting compared with nonfasting lipids and apolipoproteins for predicting incident cardiovascular events. Circulation 2008; 118 (10) 993-1001.
  • 30 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 1972; 18 (06) 499-502.
  • 31 American Diabetes Association. Standards of Medical Care in Diabetes – 2008. Diabetes Care 2008; 31 (S1): S12-S54.
  • 32 Smith Jr SC, Allen J, Blair SN. et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation 2006; 113 (19) 2363-2372.
  • 33 Ryden L, Standl E, Bartnik M. et al. Guidelines on diabetes, pre-diabetes, 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 2007; 28 (01) 88-136.
  • 34 National Cholesterol Education Program (NCEP). 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 (25) 3143-3421.
  • 35 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 (04) 355-361.
  • 36 Kannel WB, Vasan RS. Triglycerides as vascular risk factors: new epidemiologic insights. Curr Opin Cardiol 2009; 24 (04) 345-350.
  • 37 Walldius G, Jungner I, Holme I. et al. High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet 2001; 358 9298 2026-2033.
  • 38 Yusuf S, Hawken S, Ounpuu S. et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364 9438 937-952.
  • 39 Barter PJ, Ballantyne CM, Carmena R. et al. Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ ten-country panel. J Intern Med 2006; 259 (03) 247-258.
  • 40 Wang J, Ban MR, Zou GY. et al. Polygenic determinants of severe hypertriglyceridemia. Hum Mol Genet 2008; 17 (18) 2894-2899.