Labordiagnostik von Fettstoffwechselstörungen

ZUSAMMENFASSUNG

Fettstoffwechselstörungen zeigen häufig keine klinischen Symptome, einzig Hauterscheinungen können auf einen gestörten Fettstoffwechsel hinweisen. Daher sind weitreichende Laboruntersuchungen für die Diagnostik ausschlaggebend. Dieser Artikel zeigt die basisdiagnostischen Möglichkeiten zur Verifizierung einer Fettstoffwechselstörung auf, befasst sich mit ergänzenden Laboruntersuchungen und nennt therapeutische Zielgrößen.

Publication History

Article published online:
21 May 2024

• Literatur

• 1 Mach F, Baigent C, Catapano AL. et al 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41: 111-188 DOI: 10.1093/eurheartj/ehz455.
• 2 Visseren FLJ, Mach F, Smulders YM. et al 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2021; 42: 3227-3337 DOI: 10.1093/eurheartj/ehab484.
• 3 Blanke P.. The distribution of lipoprotein concentrations in Germany. in preparation. 2023
• 4 März W, Beil FU, Dieplinger H. Genetic diseases of lipid metabolism – Focus familial hypercholesterolemia. Dtsch Med Wochenschr 2022; 147: e50-e61 DOI: 10.1055/a-1516-2541.
• 5 März W, Grammer TB, Delgado G. et al Congenital disorders of lipoprotein metabolism. Herz 2017; 42: 449-458 DOI: 10.1007/s00059-017-4578-x.
• 6 Katzmann JL, Lehmann M, Tunnemann-Tarr A. et al Cutaneous manifestations in familial hypercholesterolaemia. Atherosclerosis 2021; 333: 116-123 DOI: 10.1016/j.atherosclerosis.2021.07.007.
• 7 Langlois MR, Chapman MJ, Cobbaert C. et al Quantifying atherogenic lipoproteins: Current and future challenges in the era of personalized medicine and very low concentrations of LDL cholesterol. A consensus statement from EAS and EFLM. Clin Chem 2018; 64: 1006-1033 DOI: 10.1373/clinchem.2018.287037.
• 8 Kassenärztliche Bundesvereinigung. Gesundheitsvorsorge: Der Check-up für Erwachsene. Im Internet (Stand: 04.09.2023) www.kbv.de/html/3500.php
• 9 Fath F, Bengeser A, Barresi M. et al FH ALERT: Efficacy of a novel approach to identify patients with familial hypercholesterolemia. Sci Rep 2021; 11: 20421 DOI: 10.1038/s41598-021-99961-y.
• 10 Gemeinsamer Bundesausschuss. Kinderuntersuchungsheft. Im Internet (Stand: 04.09.2023): www.g-ba.de/downloads/17-98-4160/2023-05-12_G-BA_Kinderuntersuchungsheft_WEB_WZ_PW.pdf
• 11 Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Summary Report Pediatrics. 2011; 128 (Suppl. 05) S213-S256 DOI: 10.1542/peds.2009-2107C.
• 12 Daniels SR, Gidding SS, de Ferranti SD. et al Pediatric aspects of familial hypercholesterolemias: recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. Journal of Clinical Lipidology 2011; 05: S30-S37 DOI: 10.1016/j.jacl.2011.03.453.
• 13 Luirink IK, Wiegman A, Kusters DM. et al 20-Year follow-up of statins in children with familial hypercholesterolemia. N Engl J Med 2019; 381: 1547-1556 DOI: 10.1056/NEJMoa1816454.
• 14 Ference BA, Ginsberg HN, Graham I. et al Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2017; 38: 2459-2472 DOI: 10.1093/eurheartj/ehx144.
• 15 Klose G, Laufs U, März W. et al Familial hypercholesterolemia: Developments in diagnosis and treatment. Deutsches Ärzteblatt international 2014; 111: 523-529 DOI: 10.3238/arztebl.2014.0523.
• 16 U.S. Department of Health and Human Services. Public Health Service. National Institutes of Health. Manual of laboratory operations: lipid and lipoprotein analysis (revised). US Government Printing Office, Washington, DC Report No: (NIH) 75-67815. 1982
• 17 Nauck M, Winkler K, März W. et al Quantitative determination of high-, low-, and very-low-density lipoproteins and lipoprotein(a) by agarose gel electrophoresis and enzymatic cholesterol staining. Clin Chem 1995; 41: 1761-1767
• 18 Nauck M, Winkler K, Wittmann C. et al Direct determination of lipoprotein(a) cholesterol by ultracentrifugation and agarose gel electrophoresis with enzymatic staining for cholesterol. Clin Chem 1995; 41: 731-738
• 19 Rief M, Raggam R, Rief P. et al Comparison of two nuclear magnetic resonance spectroscopy methods for the measurement of lipoprotein particle concentrations. Biomedicines 2022: 10 DOI: 10.3390/biomedicines10071766
• 20 Siekmeier R, März W, Groß W.. Precipitation of low density lipoproteins with sulfated polyanions: Three methdod compared. Clin Chem 1988; 177: 221-230
• 21 Siekmeier R, März W, Groß W.. Insufficient accuracy and specificity of polyanion precipitation methods for the quantitation of low density lipoproteteins. Clin Chem 1990; 36: 2109-2113
• 22 Nauck M, Warnick GR, Rifai N. Methods for measurement of LDL-cholesterol: a critical assessment of direct measurement by homogeneous assays versus calculation. Clin Chem 2002; 48: 236-254
• 23 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: 499-502
• 24 Martin SS, Blaha MJ, Elshazly MB. et al Friedewald-estimated versus directly measured low-density lipoprotein cholesterol and treatment implications. J Am Coll Cardiol 2013; 62: 732-739 DOI: 10.1016/j.jacc.2013.01.079.
• 25 Sampson M, Ling C, Sun Q. et al A new equation for calculation of low-density lipoprotein cholesterol in patients with normolipidemia and/or hypertriglyceridemia. JAMA Cardiol 2020; 05: 540-548 DOI: 10.1001/jamacardio.2020.0013.
• 26 Wadstrom BN, Pedersen KM, Wulff AB. et al Elevated remnant cholesterol, plasma triglycerides, and cardiovascular and noncardiovascular mortality. Eur Heart J 2023; 44: 1432-1445 DOI: 10.1093/eurheartj/ehac822.
• 27 Scharnagl H, Kleber ME, März W. Letter by Scharnagl, et al regarding article, “Elevated remnant cholesterol causes both low-grade inflammation and ischemic heart disease, whereas elevated low-density lipoprotein cholesterol causes ischemic heart disease without inflammation”. Circulation 2014; 129: e654 DOI: 10.1161/CIRCULATIONAHA.113.006433.
• 28 Bundesärztekammer. Richtlinie der Bundesärztekammer zur Qualitätssicherung laboratoriumsmedizinischer Untersuchungen. 2023 https://www.rfb.bio/pdf/Rili-BAEK-05-2023.pdf
• 29 MacDonald R. Quality assessment of quantitative analytical results inlaboratory medicine by root mean square of measurementdeviation. J Lab Med 2006; 30 (03) 111-117
• 30 Scharnagl H, Nauck M, Wieland H. et al The Friedewald formula underestimates LDL cholesterol at low concentrations. Clin Chem Lab Med 2001; 39: 426-431 DOI: 10.1515/CCLM.2001.068.
• 31 Miller WG, Myers GL, Sakurabayashi I. et al Seven direct methods for measuring HDL and LDL cholesterol compared with ultracentrifugation reference measurement procedures. Clin Chem 2010; 56: 977-986 DOI: 10.1373/clinchem.2009.142810.
• 32 Miida T, Nishimura K, Okamura T. et al Validation of homogeneous assays for HDL-cholesterol using fresh samples from healthy and diseased subjects. Atherosclerosis 2014; 233: 253-259 DOI: 10.1016/j.atherosclerosis.2013.12.033.
• 33 Vesper HW, Wilson PW, Rifai N. A message from the laboratory community to the National Cholesterol Education Program Adult Treatment Panel IV. Clin Chem 2012; 58: 523-527 DOI: 10.1373/clinchem.2011.178202.
• 34 Langlois MR, Descamps OS, van der Laarse A. et al Clinical impact of direct HDLc and LDLc method bias in hypertriglyceridemia. A simulation study of the EAS-EFLM Collaborative Project Group. Atherosclerosis 2014; 233: 83-90 DOI: 10.1016/j.atherosclerosis.2013.12.016.
• 35 Di Angelantonio E, Sarwar N, Perry P. et al Major lipids, apolipoproteins, and risk of vascular disease. JAMA 2009; 302: 1993-2000 DOI: 10.1001/jama.2009.1619.
• 36 von Eckardstein A, Nordestgaard BG, Remaley AT. et al Highdensity lipoprotein revisited: biological functions and clinical relevance. Eur Heart J 2022 DOI: 10.1093/eurheartj/ehac605
• 37 von Eckardstein A, März W, Laufs U.. HDL – quo vadis? Dtsch Med Wochenschr. 2023 DOI: 10.1055/a-1516-2731
• 38 van der Steeg WA, Holme I, Boekholdt SM. et al High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: significance for cardiovascular risk: the IDEAL and EPIC-Norfolk studies. J Am Coll Cardiol 2008; 51: 634-642 DOI: 10.1016/j.jacc.2007.09.060.
• 39 Madsen CM, Varbo A, Nordestgaard BG. Extreme high highdensity lipoprotein cholesterol is paradoxically associated with high mortality in men and women: two prospective cohort studies. Eur Heart J 2017; 38: 2478-2486 DOI: 10.1093/eurheartj/ehx163.
• 40 Zewinger S, Speer T, Kleber ME. et al HDL cholesterol is not associated with lower mortality in patients with kidney dysfunction. Journal of the American Society of Nephrology: JASN 2014; 25: 1073-1082 DOI: 10.1681/ASN.2013050482.
• 41 Zewinger S, Drechsler C, Kleber ME. et al Serum amyloid A: high-density lipoproteins interaction and cardiovascular risk. Eur Heart J 2015; 36: 3007-3016 DOI: 10.1093/eurheartj/ehv352.
• 42 Zewinger S, Kleber ME, Rohrer L. et al Symmetric dimethylarginine, high-density lipoproteins and cardiovascular disease. Eur Heart J 2017; 38: 1597-1607 DOI: 10.1093/eurheartj/ehx118.
• 43 März W, Kleber ME, Scharnagl H. et al HDL cholesterol: reappraisal of its clinical relevance. Clinical research in cardiology: official journal of the German Cardiac Society 2017; 106 (09) 663-675 DOI: 10.1007/s00392-017-1106-1.
• 44 März W, Kleber ME, Scharnagl H. et al [Clinical importance of HDL cholesterol]. Herz 2017; 42: 58-66 DOI: 10.1007/s00059-016-4499-0.
• 45 Ritsch A, Scharnagl H, März W.. HDL cholesterol efflux capacity and cardiovascular events. N Engl J Med 2015; 372: 1870-1871 DOI: 10.1056/NEJMc1503139#SA3.
• 46 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: 2109-2122 DOI: 10.1056/NEJMoa0706628.
• 47 Schwartz GG, Olsson AG, Abt M. et al Effects of Dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med 2012; 367: 2089-2099 DOI: 10.1056/NEJMoa1206797.
• 48 Group HTRC, Bowman L, Hopewell JC. et al Effects of Anacetrapib in patients with atherosclerotic vascular disease. N Engl J Med 2017; 377: 1217-1227 DOI: 10.1056/NEJMoa1706444.
• 49 März W, Blanke P, Gouni-Berthold I. et al Schwere Hypertriglyzeridämien – Konsensus zur Klassifikation, Diagnostik und Behandlung. in Vorbereitung. 2023
• 50 Mikhailidis DP, Elisaf M, Rizzo M. et al “European panel on low density lipoprotein (LDL) subclasses”: a statement on the pathophysiology, atherogenicity and clinical significance of LDL subclasses. Current Vascular Pharmacology 2011; 09: 533-571 DOI: 10.2174/157016111796642661.
• 51 Sarwar N, Sandhu MS, Ricketts SL. et al Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet 2010; 375: 1634-1639 DOI: 10.1016/S0140-6736(10)60545-4.
• 52 Varbo A, Benn M, Tybjaerg-Hansen A. et al Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol 2013; 61: 427-436 DOI: 10.1016/j.jacc.2012.08.1026.
• 53 Crosby J, Peloso GM, Auer PL. et al Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N Engl J Med 2014; 371: 22-31 DOI: 10.1056/NEJMoa1307095.
• 54 Jorgensen AB, Frikke-Schmidt R, Nordestgaard BG. et al Lossof-function mutations in APOC3 and risk of ischemic vascular disease. N Engl J Med 2014; 371: 32-41 DOI: 10.1056/NEJMoa1308027.
• 55 Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet 2014; 384: 626-635 DOI: 10.1016/S0140-6736(14)61177-6.
• 56 Merkel M, Muller-Wieland D, Laufs U. et al Triglycerides – assessment as risk factor and therapeutic goals. Dtsch Med Wochenschr 2022; 147: 1286-1295 DOI: 10.1055/a-1516-2661.
• 57 März W, Scharnagl H, Winkler K. et al Low-density lipoprotein triglycerides associated with low-grade systemic inflammation, adhesion molecules, and angiographic coronary artery disease: the Ludwigshafen Risk and Cardiovascular Health stu-dy. Circulation 2004; 110: 3068-3074 DOI: 10.1161/01.CIR.0000146898.06923.80.
• 58 Silbernagel G, Scharnagl H, Kleber ME. et al LDL triglycerides, hepatic lipase activity, and coronary artery disease: An epidemiologic and Mendelian randomization study. Atherosclerosis 2019; 282: 37-44 DOI: 10.1016/j.atherosclerosis.2018.12.024.
• 59 Balling M, Afzal S, Davey Smith G. et al Elevated LDL triglycerides and atherosclerotic risk. J Am Coll Cardiol 2023; 81: 136-152 DOI: 10.1016/j.jacc.2022.10.019.
• 60 Fredrickson DS, Levy RI, Lees RS. Fat transport in lipoproteins – an integrated approach to mechanisms and disorders. N Engl J Med 1967; 276: 34-44 94–103, 148–156, 215–225, 273–281
• 61 Moulin P, Dufour R, Averna M. et al Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): Expert panel recommendations and proposal of an “FCS score”. Atherosclerosis 2018; 275: 265-272 DOI: 10.1016/j.atherosclerosis.2018.06.814.
• 62 Bardey F, Rieck L, Spira D. et al Clinical characterization and mutation spectrum of patients with hypertriglyceridemia in a German outpatient clinic. 2023
• 63 Nauck M, Winkler K, Siekmeier R. et al Pseudo-pseudohypertriglyceridemia: a case of increased free glycerol without evidence for glycerol kinase deficiency. Clin Chem 1995; 41: 619-620
• 64 Kostner KM, März W, Kostner GM. When should we measure lipoprotein(a)?. Eur Heart J 2013; 34: 3268-3276 DOI: 10.1093/eurheartj/eht053.
• 65 Reuser A, Koenig W, Laufs U. Lp(a) and its role in cardiovascular diseases. Dtsch Med Wochenschr 2022; 147: 1564-1570 DOI: 10.1055/a-1516-2701.
• 66 Kronenberg F, Mora S, Stroes ESG. et al Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: A European Atherosclerosis Society consensus statement. Eur Heart J 2022; 43: 3925-3946 DOI: 10.1093/eurheartj/ehac361.
• 67 Schatz U, Fischer S, Muller G. et al Cardiovascular risk factors in patients with premature cardiovascular events attending the University of Dresden Lipid Clinic. Atherosclerosis Supplements 2019; 40: 94-99 DOI: 10.1016/j.atherosclerosissup.2019.08.044.
• 68 Yeang C, Witztum JL, Tsimikas S. Novel method for quantification of lipoprotein(a)-cholesterol: implications for improving accuracy of LDL-C measurements. J Lipid Res 2021; 62: 100053 DOI: 10.1016/j.jlr.2021.100053.
• 69 Nordestgaard BG, Langlois MR, Langsted A. et al Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM. Atherosclerosis 2020; 294: 46-61 DOI: 10.1016/j.atherosclerosis.2019.12.005.
• 70 Nordestgaard BG, Langsted A, Mora S. et al Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cut-points-a joint consensus statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine. Eur Heart J 2016; 37: 1944-1958 DOI: 10.1093/eurheartj/ehw152.
• 71 Scharnagl H, Stojakovic T, Dieplinger B. et al Comparison of lipoprotein (a) serum concentrations measured by six commercially available immunoassays. Atherosclerosis 2019; 289: 206-213 DOI: 10.1016/j.atherosclerosis.2019.08.015.
• 72 Gemeinsamer Bundesausschuss. Richtlinie des Gemeinsamen Bundesausschusses zu Untersuchungs- und Behandlungsmethoden der vertragsärztlichen Versorgung. Richtlinie Methoden vertragsärztliche Versorgung, in der Fassung vom 17. Januar 2006, veröffentlicht imBundesanzeiger 2006 Nr. 48 (S. 1 523), in Kraft getreten am 1. April 2006, zuletzt geändert am 19. Februar 2015, veröffentlicht im Bundesanzeiger (Banz AT 15.05.2015 B7), in Kraft getreten am 16. Mai 2015
• 73 Gesellschaft Prävention von Herz-Kreislauf-Erkrankungen e.V. Vergleich quantitativer Bestimmungsmethoden für Lipoprotein (a) (Oktober 2015). Im Internet (Stand: 04.09.2023): www.dach-praevention.eu/wissenschaftlicher-beitrag/vergleich-quantitativer-bestimmungsmethoden-fuer-lipoprotein-a/
• 74 Catapano AL, Graham I, De Backer G. et al 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis 2016; 253: 281-344 DOI: 10.1016/j.atherosclerosis.2016.08.018.
• 75 Cegla J, Neely RDG, France M. et al Heart UK consensus statement on Lipoprotein(a): A call to action. Atherosclerosis 2019; 291: 62-70 DOI: 10.1016/j.atherosclerosis.2019.10.011.
• 76 Albers JJ, Slee A, O’Brien KD. et al Relationship of apolipoproteins A-1 and B, and lipoprotein(a) to cardiovascular outcomes: the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes). J Am Coll Cardiol 2013; 62: 1575-1579 DOI: 10.1016/j.jacc.2013.06.051.
• 77 Darling GM, Johns JA, McCloud PI. et al Concurrent use of simvastatin and estrogen–progestin therapy compared with each therapy alone for hypercholesterolemia in postmenopausal women. Climacteric 1999; 02: 181-188 DOI: 10.3109/13697139909038060.
• 78 Stein EA, Honarpour N, Wasserman SM. et al Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation 2013; 128: 2113-2120 DOI: 10.1161/CIRCULATIONAHA.113.004678.
• 79 Bea AM, Cenarro A, Marco-Bened V. et al Diagnosis of familial dysbetalipoproteinemia based on the lipid abnormalities driven by APOE2 / E2 genotype. Clin Chem 2023; 69: 140-148 DOI: 10.1093/clinchem/hvac213.
• 80 Grammer TB, Kleber ME, MärzWet al. Low-density lipoprotein particle diameter and mortality: the Ludwigshafen Risk and Cardiovascular Health Study. Eur Heart J 2015; 36: 31-38 DOI: 10.1093/eurheartj/ehu055.
• 81 Baca AM, Warnick GR. Estimation of LDL-associated apolipoprotein B from measurements of triglycerides and total apolipoprotein B. Clin Chem 2008; 54: 907-910 DOI: 10.1373/clinchem.2007.100941.
• 82 Silbernagel G, Scharnagl H, Saely CH. et al The LDL apolipoprotein B-to-LDL cholesterol ratio: Association with cardiovascular mortality and a biomarker of small, dense LDLs. Biomedicines 2022: 10 DOI: 10.3390/biomedicines10061302
• 83 Mora S, Otvos JD, Rifai N. et al Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women. Circulation 2009; 119: 931-939 DOI: 10.1161/CIRCULATIONAHA.108.816181.
• 84 März W, Feussner G, Siekmeier R. et al The apolipoprotein B to E ratio: A marker for type III hyperlipoproteinemia. Eur J Clin Chem Clin Biochem 1993; 31: 743-747
• 85 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: 2026-2033
• 86 Di Angelantonio E, Gao P.. Emerging Risk Factors C, et al. Lipidrelated markers and cardiovascular disease prediction. JAMA 2012; 307: 2499-2506 DOI: 10.1001/jama.2012.6571.
• 87 Nauck MS, Nissen H, Hoffmann MM. et al Detection of mutations in the apolipoprotein CII gene by denaturing gradient gel electrophoresis. Identification of the splice site variant apolipoprotein CII-Hamburg in a patient with severe hypertriglyceridemia. Clin Chem 1998; 44: 1388-1396
• 88 Silbernagel G, Chen YQ, Rief M. et al Inverse association between apolipoprotein C-II and cardiovascular mortality: role of lipoprotein lipase activity modulation. Eur Heart J 2023; 44: 2335-2345 DOI: 10.1093/eurheartj/ehad261.
• 89 Nordestgaard BG, Langsted A, Mora S. et al Fasting Is Not Routinely Required for Determination of a Lipid Profile: Clinical and Laboratory Implications Including Flagging at Desirable Concentration Cutpoints-A Joint Consensus Statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine. Clin Chem 2016; 62: 930-946 DOI: 10.1373/clinchem.2016.258897.
• 90 European Association of Prevetive Cardiology https://www.escardio.org/Education/Practice-Tools/CVD-prevention-toolbox/HeartScore
• 91 Marks D, Thorogood M, Neil HA. et al A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis 2003; 168: 1-14 DOI: 10.1016/s0021-9150(02)00330-1.
• 92 Hevonoja T, Pentikainen MO, Hyvonen MT. et al Structure of low density lipoprotein (LDL) particles: basis for understanding molecular changes in modified LDL. Biochim Biophys Acta 2000; 1488: 189-210 DOI: 10.1016/s1388-1981(00)00123-2.
• 93 Baumstark MW, Kreutz W, Berg A. et al Structure of human lowdensity lipoprotein subfractions, determined by X-ray smallangle scattering. Biochim Biophys Acta 1990; 1037: 48-57