nach oben

Erschienen in:

23.05.2016 | Lipidstoffwechselstörungen | Schwerpunkt

Einfluss der Lipidstoffwechselparameter auf die Entstehung und Progression der koronaren Herzerkrankung

Ein Update

verfasst von: D. Sinning, D. M. Leistner, Prof. Dr. med. U. Landmesser

Erschienen in: Herz | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

Zusammenfassung

Bei der Entstehung und Progression der koronaren Herzerkrankung (KHK) spielen Lipidstoffwechselstörungen eine entscheidende Rolle. Lipidstoffwechselstörungen stellen deshalb für die Prävention und Therapie der KHK ein zentrales Therapieziel dar. Epidemiologische Studien zeigen eine Assoziation zwischen bestimmten Parametern des Lipidstoffwechsels und dem Risiko, eine KHK zu entwickeln, bzw. dem Risiko für eine Progression bei bestehender KHK. Insbesondere ein erhöhtes LDL („low-density lipoprotein“)-Cholesterin, niedriges HDL („high-density lipoprotein“)-Cholesterin, hohe Triglyzeridwerte und erhöhte Lipoprotein(a) [Lp(a)]-Spiegel können bei der Risikostratifizierung von Patienten in der kardiovaskulären Prävention Beachtung finden. Bei der Primär- und Sekundärprävention der KHK steht aktuell die Prognoseverbesserung durch eine Senkung des LDL-Cholesterins mittels Ernährungs-/Lebensstiländerungen und intensiver Statintherapie, ggf. erweitert durch eine Ezetimibtherapie, im Vordergrund therapeutischer Bemühungen. Zum besseren Verständnis der Beziehung zwischen Lipidstoffwechselstörungen und kardiovaskulärem Risiko haben zuletzt auch genetische Studien beigetragen, wobei eine kausale Rolle des LDL-C, des Lp(a) und triglyzeridreicher Lipoproteine (TRL) für die Progression der KHK gezeigt werden konnte, was für das HDL-C in verschiedenen Studien nicht beobachtet wurde. Weiterhin wird der Effekt einer LDL-C-Senkung durch PCSK9 (Proproteinkonvertase Subtilisin/Kexin Typ 9)-Hemmung bzw. durch den CETP (Cholesterinestertransferprotein)-Inhibitor Anacetrapib auf kardiovaskuläre Ereignisse aktuell in großen klinischen Studienprogrammen untersucht.

Mathers CD, Loncar D (2006) Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 3(11):e442 doi:10.1371/journal.pmed.0030442PubMedPubMedCentralCrossRef

Ford ES, Ajani UA, Croft JB, Critchley JA, Labarthe DR, Kottke TE, Giles WH, Capewell S (2007) Explaining the decrease in U.S. deaths from coronary disease, 1980–2000. N Engl J Med 356(23):2388–2398. doi:10.1056/NEJMsa053935PubMedCrossRef

Emerging Risk Factors Collaborations, Angelantonio E Di, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, Wood AM, Lewington S, Sattar N, Packard CJ, Collins R, Thompson SG, Danesh J (2009) Major lipids, apolipoproteins, and risk of vascular disease. JAMA 302(18):1993–2000. doi:10.1001/jama.2009.1619CrossRef

Global Lipids Genetics Consortium, Willer CJ, Schmidt EM, Sengupta S, Peloso GM, Gustafsson S et al (2013) Discovery and refinement of loci associated with lipid levels. Nat Genet 45(11):1274–1283. doi:10.1038/ng.2797CrossRef

Niccoli G, Montone RA, Di Vito L, Gramegna M, Refaat H, Scalone G, Leone AM, Trani C, Burzotta F, Porto I, Aurigemma C, Prati F, Crea F (2015) Plaque rupture and intact fibrous cap assessed by optical coherence tomography portend different outcomes in patients with acute coronary syndrome. Eur Heart J 36(22):1377–1384. doi:10.1093/eurheartj/ehv029PubMedCrossRef

National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (1993) Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II. JAMA 269(23):3015–3023CrossRef

Ross R (1999) Atherosclerosis – an inflammatory disease. N Engl J Med 340(2):115–126. doi:10.1056/NEJM199901143400207PubMedCrossRef

Stamler J, Wentworth D, Neaton JD (1986) Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the multiple risk factor intervention trial (MRFIT). JAMA 256(20):2823–2828PubMedCrossRef

Birgelen C von, Hartmann M, Mintz GS, Baumgart D, Schmermund A, Erbel R (2003) Relation between progression and regression of atherosclerotic left main coronary artery disease and serum cholesterol levels as assessed with serial long-term (> or =12 months) follow-up intravascular ultrasound. Circulation 108(22):2757–2762. doi:10.1161/01.CIR.0000103664.47406.49CrossRef

10.

Birgelen C von, Hartmann M, Mintz GS, Houwelingen KG van, Deppermann N, Schmermund A, Bose D, Eggebrecht H, Neumann T, Gossl M, Wieneke H, Erbel R (2004) Relationship between cardiovascular risk as predicted by established risk scores versus plaque progression as measured by serial intravascular ultrasound in left main coronary arteries. Circulation 110(12):1579–1585. doi:10.1161/01.CIR.0000142048.94084.CACrossRef

11.

National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002) 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 106(25):3143–3421

12.

Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr., Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr., Stone NJ, National Heart, Lung, and Blood Institute, American College of Cardiology Foundation, American Heart Association (2004) Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. Circulation 110(2):227–239. doi:10.1161/01.CIR.0000133317.49796.0EPubMedCrossRef

13.

Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R (2010) Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376(9753):1670–1681. doi:10.1016/S0140-6736(10)61350-5CrossRef

14.

Perk J, Backer G De, Gohlke H, Graham I, Reiner Z, Verschuren WM, Albus C, Benlian P, Boysen G, Cifkova R, Deaton C, Ebrahim S, Fisher M, Germano G, Hobbs R, Hoes A, Karadeniz S, Mezzani A, Prescott E, Ryden L, Scherer M, Syvanne M, Scholte op Reimer WJ, Vrints C, Wood D, Zamorano JL, Zannad F, European Association for Cardiovascular Prevention & Rehabilitation (EACPR), ESC Committee for Practice Guidelines (CPG) (2012) European guidelines on cardiovascular disease prevention in clinical practice (version 2012) : the fifth joint task force of the European society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Int J Behav Med 19(4):403–488. doi:10.1007/s12529-012-9242-5PubMedCrossRef

15.

Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, Davignon J, Erbel R, Fruchart JC, Tardif JC, Schoenhagen P, Crowe T, Cain V, Wolski K, Goormastic M, Tuzcu EM, ASTEROID Investigators (2006) Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA 295(13):1556–1565. doi:10.1001/jama.295.13.jpc60002PubMedCrossRef

16.

Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, Crowe T, Howard G, Cooper CJ, Brodie B, Grines CL, DeMaria AN, REVERSAL Investigators (2004) Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA 291(9):1071–1080. doi:10.1001/jama.291.9.1071PubMedCrossRef

17.

Weng TC, Yang YH, Lin SJ, Tai SH (2010) A systematic review and meta-analysis on the therapeutic equivalence of statins. J Clin Pharm Ther 35(2):139–151. doi:10.1111/j.1365-2710.2009.01085.xPubMedCrossRef

18.

Law MR, Wald NJ, Rudnicka AR (2003) Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 326(7404):1423 doi:10.1136/bmj.326.7404.1423PubMedPubMedCentralCrossRef

19.

Jones PH, Nair R, Thakker KM (2012) Prevalence of dyslipidemia and lipid goal attainment in statin-treated subjects from 3 data sources: a retrospective analysis. J Am Heart Assoc 1(6):e001800 doi:10.1161/JAHA.112.001800PubMedPubMedCentralCrossRef

20.

Stroes ES, Thompson, Corsini A, Vladutiu GD, Raal FJ, Ray KK, Roden M, Stein E, Tokgozoglu L, Nordestgaard BG, Bruckert E, Backer G De, Krauss RM, Laufs U, Santos RD, Hegele RA, Hovingh GK, Leiter LA, Mach F, Marz W, Newman CB, Wiklund O, Jacobson TA, Catapano AL, Chapman MJ, Ginsberg HN, European Atherosclerosis Society Consensus Panel (2015) Statin-associated muscle symptoms: impact on statin therapy-european atherosclerosis society consensus panel statement on assessment, Aetiology and management. Eur Heart J 36(17):1012–1022. doi:10.1093/eurheartj/ehv043PubMedPubMedCentralCrossRef

21.

Lyseng-Williamson KA (2012) Ezetimibe/simvastatin: a guide to its clinical use in hypercholesterolemia. Am J Cardiovasc Drugs 12(1):49–56. doi:10.2165/11209150-000000000-00000PubMedCrossRef

22.

Sudhop T, Lutjohann D, Kodal A, Igel M, Tribble DL, Shah S, Perevozskaya I, Bergmann K von (2002) Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation 106(15):1943–1948PubMedCrossRef

23.

Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW, Ferrari GM De, Ruzyllo W, Lucca P De, Im K, Bohula EA, Reist C, Wiviott SD, Tershakovec AM, Musliner TA, Braunwald E, Califf RM, IMPROVE-IT Investigators (2015) Ezetimibe added to Statin therapy after acute coronary syndromes. N Engl J Med 372(25):2387–2397. doi:10.1056/NEJMoa1410489PubMedCrossRef

24.

Cohen JC, Boerwinkle E, Mosley TH Jr., Hobbs HH (2006) Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354(12):1264–1272. doi:10.1056/NEJMoa054013PubMedCrossRef

25.

Holmes MV, Asselbergs FW, Palmer TM, Drenos F, Lanktree MB, Nelson CP et al (2015) Mendelian randomization of blood lipids for coronary heart disease. Eur Heart J 36(9):539–550. doi:10.1093/eurheartj/eht571PubMedCrossRef

26.

Brown MS, Goldstein JL (1986) A receptor-mediated pathway for cholesterol homeostasis. Science 232(4746):34–47PubMedCrossRef

27.

Myocardial Infarction Genetics Consortium Investigators, Stitziel NO, Won HH, Morrison AC, Peloso GM, Do R et al (2014) Inactivating mutations in NPC1L1 and protection from coronary heart disease. N Engl J Med 371(22):2072–2082. doi:10.1056/NEJMoa1405386CrossRef

28.

Ference BA, Majeed F, Penumetcha R, Flack JM, Brook RD (2015) Effect of naturally random allocation to lower low-density lipoprotein cholesterol on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both: a 2 x 2 factorial Mendelian randomization study. J Am Coll Cardiol 65(15):1552–1561. doi:10.1016/j.jacc.2015.02.020PubMedCrossRef

29.

Peterson AS, Fong LG, Young SG (2008) PCSK9 function and physiology. J Lipid Res 49(7):1595–1599PubMedPubMedCentralCrossRef

30.

Seidah NG, Awan Z, Chretien M, Mbikay M (2014) PCSK9: a key modulator of cardiovascular health. Circ Res 114(6):1022–1036. doi:10.1161/CIRCRESAHA.114.301621PubMedCrossRef

31.

Gencer B, Montecucco F, Nanchen D, Carbone F, Klingenberg R, Vuilleumier N, Aghlmandi S, Heg D, Raber L, Auer R, Juni P, Windecker S, Luscher TF, Matter CM, Rodondi N, Mach F (2016) Prognostic value of PCSK9 levels in patients with acute coronary syndromes. Eur Heart J 37(6):546–553. doi:10.1093/eurheartj/ehv637PubMedCrossRef

32.

Koren MJ, Lundqvist P, Bolognese M, Neutel JM, Monsalvo ML, Yang J, Kim JB, Scott R, Wasserman SM, Bays H, MENDEL-2 Investigators (2014) Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J Am Coll Cardiol 63(23):2531–2540. doi:10.1016/j.jacc.2014.03.018PubMedCrossRef

33.

Roth EM, McKenney JM (2015) ODYSSEY MONO: effect of alirocumab 75 mg subcutaneously every 2 weeks as monotherapy versus ezetimibe over 24 weeks. Future Cardiol 11(1):27–37. doi:10.2217/fca .14.82PubMedCrossRef

34.

Shimada YJ, Cannon CP (2015) PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitors: past, present, and the future. Eur Heart J 36(36):2415–2424. doi:10.1093/eurheartj/ehv174PubMedCrossRef

35.

Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, Stroes ES, Langslet G, Raal FJ, Shahawy M El, Koren MJ, Lepor NE, Lorenzato C, Pordy R, Chaudhari U, Kastelein JJ, ODYSSEY LONG TERM Investigators (2015) Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 372(16):1489–1499. doi:10.1056/NEJMoa1501031PubMedCrossRef

36.

Fisher EA, Feig JE, Hewing B, Hazen SL, Smith JD (2012) High-density lipoprotein function, dysfunction, and reverse cholesterol transport. Arterioscler Thromb Vasc Biol 32(12):2813–2820. doi:10.1161/ATVBAHA.112.300133PubMedPubMedCentralCrossRef

37.

Riwanto M, Rohrer L, Roschitzki B, Besler C, Mocharla P, Mueller M, Perisa D, Heinrich K, Altwegg L, Eckardstein A von, Luscher TF, Landmesser U (2013) Altered activation of endothelial anti- and proapoptotic pathways by high-density lipoprotein from patients with coronary artery disease: role of high-density lipoprotein-proteome remodeling. Circulation 127(8):891–904. doi:10.1161/CIRCULATIONAHA.112.108753PubMedCrossRef

38.

Assmann G, Schulte H, Cullen P, Seedorf U (2007) Assessing risk of myocardial infarction and stroke: new data from the prospective cardiovascular Munster (PROCAM) study. Eur J Clin Invest 37(12):925–932. doi:10.1111/j.1365-2362.2007.01888.xPubMedCrossRef

39.

Haase CL, Tybjaerg-Hansen A, Qayyum AA, Schou J, Nordestgaard BG, Frikke-Schmidt R (2012) LCAT, HDL cholesterol and ischemic cardiovascular disease: a Mendelian randomization study of HDL cholesterol in 54,500 individuals. J Clin Endocrinol Metab 97(2):E248–256. doi:10.1210/jc.2011-1846PubMedCrossRef

40.

Hewing B, Moore KJ, Fisher EA (2012) HDL and cardiovascular risk: time to call the plumber? Circ Res 111(9):1117–1120. doi:10.1161/CIRCRESAHA.112.280958PubMedPubMedCentralCrossRef

41.

Singh IM, Shishehbor MH, Ansell BJ (2007) High-density lipoprotein as a therapeutic target: a systematic review. JAMA 298(7):786–798. doi:10.1001/jama.298.7.786PubMedCrossRef

42.

Kathiresan S (2012) Will cholesteryl ester transfer protein inhibition succeed primarily by lowering low-density lipoprotein cholesterol? Insights from human genetics and clinical trials. J Am Coll Cardiol 60(20):2049–2052. doi:10.1016/j.jacc.2012.08.967PubMedCrossRef

43.

Johannsen TH, Frikke-Schmidt R, Schou J, Nordestgaard BG, Tybjaerg-Hansen A (2012) Genetic inhibition of CETP, ischemic vascular disease and mortality, and possible adverse effects. J Am Coll Cardiol 60(20):2041–2048. doi:10.1016/j.jacc.2012.07.045PubMedCrossRef

44.

Ridker PM, Pare G, Parker AN, Zee RY, Miletich JP, Chasman DI (2009) Polymorphism in the CETP gene region, HDL cholesterol, and risk of future myocardial infarction: Genomewide analysis among 18 245 initially healthy women from the Women’s Genome Health Study. Circ Cardiovasc Genet 2(1):26–33. doi:10.1161/CIRCGENETICS.108.817304PubMedPubMedCentralCrossRef

45.

Thompson A, Angelantonio E Di, Sarwar N, Erqou S, Saleheen D, Dullaart RP, Keavney B, Ye Z, Danesh J (2008) Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk. JAMA 299(23):2777–2788. doi:10.1001/jama.299.23.2777PubMedCrossRef

46.

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, ILLUMINATE Investigators (2007) Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 357(21):2109–2122. doi:10.1056/NEJMoa0706628PubMedCrossRef

47.

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, dal-OUTCOMES Investigators (2012) Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med 367(22):2089–2099. doi:10.1056/NEJMoa1206797PubMedCrossRef

48.

Cannon CP, Shah S, Dansky HM, Davidson M, Brinton EA, Gotto AM, Stepanavage M, Liu SX, Gibbons P, Ashraf TB, Zafarino J, Mitchel Y, Barter P, Barter P (2010) Safety of anacetrapib in patients with or at high risk for coronary heart disease. N Engl J Med 363(25):2406–2415. doi:10.1056/NEJMoa1009744PubMedCrossRef

49.

Nicholls SJ, Brewer HB, Kastelein JJ, Krueger KA, Wang MD, Shao M, Hu B, McErlean E, Nissen SE (2011) Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. JAMA 306(19):2099–2109. doi:10.1001/jama.2011.1649PubMedCrossRef

50.

Luscher TF, Landmesser U, Eckardstein A von, Fogelman AM (2014) High-density lipoprotein: vascular protective effects, dysfunction, and potential as therapeutic target. Circ Res 114(1):171–182. doi:10.1161/CIRCRESAHA.114.300935PubMedCrossRef

51.

Speer T, Rohrer L, Blyszczuk P, Shroff R, Kuschnerus K, Krankel N, Kania G, Zewinger S, Akhmedov A, Shi Y, Martin T, Perisa D, Winnik S, Muller MF, Sester U, Wernicke G, Jung A, Gutteck U, Eriksson U, Geisel J, Deanfield J, Eckardstein A von, Luscher TF, Fliser D, Bahlmann FH, Landmesser U (2013) Abnormal high-density lipoprotein induces endothelial dysfunction via activation of Toll-like receptor-2. Immunity 38(4):754–768. doi:10.1016/j.immuni.2013.02.009PubMedCrossRef

52.

Rohatgi A, Khera A, Berry JD, Givens EG, Ayers CR, Wedin KE, Neeland IJ, Yuhanna IS, Rader DR, Lemos JA de, Shaul PW (2014) HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med 371(25):2383–2393. doi:10.1056/NEJMoa1409065PubMedPubMedCentralCrossRef

53.

Hewing B, Landmesser U (2015) LDL, HDL, VLDL, and CVD prevention: lessons from genetics? Curr Cardiol Rep 17(7):610 doi:10.1007/s11886-015-0610-zPubMedCrossRef

54.

European Association for Cardiovascular Prevention & Rehabilitation, Reiner Z, Catapano AL, Backer G De, 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 Committee for Practice Guidelines (CPG) 2008-2010 and 2010-2012 Committees (2011) 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 32(14):1769–1818. doi:10.1093/eurheartj/ehr158CrossRef

55.

Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S, Boekholdt SM, Khaw KT, Gudnason V (2007) Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation 115(4):450–458. doi:10.1161/CIRCULATIONAHA.106.637793PubMedCrossRef

56.

ACCORD Study Group, Ginsberg HN, Elam MB, Lovato LC, Crouse JR 3rd, Leiter LA, Linz P, Friedewald WT, Buse JB, Gerstein HC, Probstfield J, Grimm RH, Ismail-Beigi F, Bigger JT, Goff DC Jr., Cushman WC, Simons-Morton DG, Byington RP (2010) Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 362(17):1563–1574. doi:10.1056/NEJMoa1001282CrossRef

57.

Investigators OT, Bosch J, Gerstein HC, Dagenais GR, Diaz R, Dyal L, Jung H, Maggiono AP, Probstfield J, Ramachandran A, Riddle MC, Ryden LE, Yusuf S (2012) n‑3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med 367(4):309–318. doi:10.1056/NEJMoa1203859CrossRef

58.

Do R, Willer CJ, Schmidt EM, Sengupta S, Gao C, Peloso GM et al (2013) Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet 45(11):1345–1352. doi:10.1038/ng.2795PubMedPubMedCentralCrossRef

59.

Jorgensen AB, Frikke-Schmidt R, Nordestgaard BG, Tybjaerg-Hansen A (2014) Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. N Engl J Med 371(1):32–41. doi:10.1056/NEJMoa1308027PubMedCrossRef

60.

TG and HDL Working Group of the Exome Sequencing Project, National Heart, Lung, and Blood Institute, Blood I, Crosby J, Peloso GM, Auer PL, Crosslin DR, Stitziel NO, Lange LA et al (2014) Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N Engl J Med 371(1):22–31. doi:10.1056/NEJMoa1307095CrossRef

61.

Graham MJ, Lee RG, Bell TA 3rd, Fu W, Mullick AE, Alexander VJ, Singleton W, Viney N, Geary R, Su J, Baker BF, Burkey J, Crooke ST, Crooke RM (2013) Antisense oligonucleotide inhibition of apolipoprotein C‑III reduces plasma triglycerides in rodents, nonhuman primates, and humans. Circ Res 112(11):1479–1490. doi:10.1161/CIRCRESAHA.111.300367PubMedCrossRef

62.

Berg K (1963) A new serum type system in man – the Lp system. Acta Pathol Microbiol Scand 59:369–382PubMedCrossRef

63.

Utermann G (1989) The mysteries of lipoprotein(a). Science 246(4932):904–910PubMedCrossRef

64.

Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25(12):677–686. doi:10.1016/j.it.2004.09.015PubMedCrossRef

65.

Leischik R, Dworrak B (2006) Lipoprotein(a): importance for the fibrinolytic system and thromboembolic complications. Herz 31(2):144–152. doi:10.1007/s00059-006-2714-0PubMedCrossRef

66.

Schmitz G, Orso E (2015) Lipoprotein(a) hyperlipidemia as cardiovascular risk factor: pathophysiological aspects. Clin Res Cardiol supplements 10:21–25. doi:10.1007/s11789-015-0074-0

67.

Kamstrup PR, Tybjaerg-Hansen A, Nordestgaard BG (2013) Extreme lipoprotein(a) levels and improved cardiovascular risk prediction. J Am Coll Cardiol 61(11):1146–1156. doi:10.1016/j.jacc.2012.12.023PubMedCrossRef

68.

Nordestgaard BG, Chapman MJ, Ray K, Boren J, Andreotti F, Watts GF, Ginsberg H, Amarenco P, Catapano A, Descamps OS, Fisher E, Kovanen PT, Kuivenhoven JA, Lesnik P, Masana L, Reiner Z, Taskinen MR, Tokgozoglu L, Tybjaerg-Hansen A, European Atherosclerosis Society Consensus P (2010) Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J 31(23):2844–2853. doi:10.1093/eurheartj/ehq386PubMedPubMedCentralCrossRef

69.

Berg K, Dahlen G, Christophersen B, Cook T, Kjekshus J, Pedersen T (1997) Lp(a) lipoprotein level predicts survival and major coronary events in the Scandinavian Simvastatin survival study. Clin Genet 52(5):254–261PubMedCrossRef

70.

Thomas HP, Steinhagen-Thiessen E (2003) Lipoprotein(a): Aspects of pathophysiology, epidemiology and treatment. Z Kardiol 92(Suppl 3):III53–III58. doi:10.1007/s00392-003-1308-6PubMed

71.

Rubin J, Kim HJ, Pearson TA, Holleran S, Berglund L, Ramakrishnan R (2008) The apolipoprotein(a) gene: linkage disequilibria at three loci differs in African Americans and Caucasians. Atherosclerosis 201(1):138–147. doi:10.1016/j.atherosclerosis.2008.01.002PubMedPubMedCentralCrossRef

72.

Chretien JP, Coresh J, Berthier-Schaad Y, Kao WH, Fink NE, Klag MJ, Marcovina SM, Giaculli F, Smith MW (2006) Three single-nucleotide polymorphisms in LPA account for most of the increase in lipoprotein(a) level elevation in African Americans compared with European Americans. J Med Genet 43(12):917–923. doi:10.1136/jmg.2006.042119PubMedPubMedCentralCrossRef

73.

Brown BG, Zhao XQ, Chait A, Fisher LD, Cheung MC, Morse JS, Dowdy AA, Marino EK, Bolson EL, Alaupovic P, Frohlich J, Albers JJ (2001) Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 345(22):1583–1592. doi:10.1056/NEJMoa011090PubMedCrossRef

74.

Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald W (1986) Fifteen year mortality in coronary drug project patients: long-term benefit with niacin. J Am Coll Cardiol 8(6):1245–1255PubMedCrossRef

75.

HPS2-THRIVE Collaborative Group (2013) HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment. Eur Heart J 34(17):1279–1291. doi:10.1093/eurheartj/eht055PubMedCentralCrossRef

76.

AIM-HIGH Investigators, Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, McBride R, Teo K, Weintraub W (2011) Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 365(24):2255–2267. doi:10.1056/NEJMoa1107579CrossRef

77.

Tsujita K, Sugiyama S, Sumida H, Shimomura H, Yamashita T, Yamanaga K, Komura N, Sakamoto K, Oka H, Nakao K, Nakamura S, Ishihara M, Matsui K, Sakaino N, Nakamura N, Yamamoto N, Koide S, Matsumura T, Fujimoto K, Tsunoda R, Morikami Y, Matsuyama K, Oshima S, Kaikita K, Hokimoto S, Ogawa H (2015) Impact of Dual Lipid-Lowering Strategy With Ezetimibe and Atorvastatin on Coronary Plaque Regression in Patients With Percutaneous Coronary Intervention: The Multicenter Randomized Controlled PRECISE-IVUS Trial. J Am Coll Cardiol 66(5):495–507. doi:10.1016/j.jacc.2015.05.065PubMedCrossRef

78.

Tibolla G, Norata GD, Artali R, Meneghetti F, Catapano AL (2011) Proprotein convertase subtilisin/kexin type 9 (PCSK9): from structure-function relation to therapeutic inhibition. Nutrition, metabolism, and cardiovascular diseases. NMCD 21(11):835–843. doi:10.1016/j.numecd.2011.06.002PubMed

Titel: Einfluss der Lipidstoffwechselparameter auf die Entstehung und Progression der koronaren Herzerkrankung
Ein Update
verfasst von: D. Sinning
D. M. Leistner
Prof. Dr. med. U. Landmesser
Publikationsdatum: 23.05.2016
Verlag: Springer Medizin
Schlagwörter: Lipidstoffwechselstörungen
Koronare Herzerkrankung
Prävention in der Diabetologie
Erschienen in: Herz / Ausgabe 4/2016
Print ISSN: 0340-9937
Elektronische ISSN: 1615-6692
DOI: https://doi.org/10.1007/s00059-016-4430-8

Neu im Fachgebiet Kardiologie

24.04.2024 | DGIM 2024 | Kongressbericht | Nachrichten

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Einfluss der Lipidstoffwechselparameter auf die Entstehung und Progression der koronaren Herzerkrankung

Ein Update

Zusammenfassung

Neu im Fachgebiet Kardiologie

Myokarditis nach Infekt – richtig schwierig wird es bei Profisportlern

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

Europäische Ernährungsgewohnheiten: Das sind die häufigsten Fehler

Parodontalbehandlung verbessert Prognose bei Katheterablation

Update Kardiologie

Springer Medizin

Zusammenfassung

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2016

Patient satisfaction in cardiology after cardiac catheterization

Koronare mikrovaskuläre Dysfunktion

PCSK9-Inhibitoren

PCSK9-Inhibitoren

Einführung der PCSK9-Inhibitoren

Establishing a low-expression renalase gene model in cardiac tissue of Sprague–Dawley rats

Neu im Fachgebiet Kardiologie

Myokarditis nach Infekt – richtig schwierig wird es bei Profisportlern

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

Europäische Ernährungsgewohnheiten: Das sind die häufigsten Fehler

Parodontalbehandlung verbessert Prognose bei Katheterablation

Update Kardiologie