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21.10.2016 | übersicht

LDL-Cholesterin und kardiovaskuläre Ereignisse: je niedriger desto besser?

verfasst von: Prim. Univ.-Doz. Dr. Raimund Weitgasser, Dr. Michaela Ratzinger, Dr. Margit Hemetsberger, Prim. Univ. Prof. Dr. Peter Siostrzonek

Erschienen in: Wiener Medizinische Wochenschrift | Ausgabe 5-6/2018

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Zusammenfassung

Seit über 30 Jahren wird die Rolle des LDL-Cholesterins in der Entstehung von kardiovaskulären Erkrankungen untersucht. Große Studien mit Statinen zeigten in diversen Settings, dass der LDL-Cholesterinspiegel mit der kardiovaskulären Ereignisrate assoziiert ist. Diese Assoziation wird häufig als „LDL-Cholesterinhypothese“ bezeichnet. Neuere Studien zu Wirkstoffen mit gänzlich anderen Wirkmechanismen bestätigten diese Assoziation und zeigten darüber hinaus, dass es einen kausalen Zusammenhang zwischen geringeren LDL-Cholesterinspiegeln und besseren kardiovaskulären Outcomes zu geben scheint und man somit vom „LDL-Cholesterinprinzip“ sprechen kann. Es ist zu erwarten, dass derzeit laufende Outcome-Studien die Annahme eines kausalen Zusammenhangs weiter untermauern werden, mit der Aussicht den Behandlern ein besseres an die Bedürfnisse der einzelnen Patienten angepasstes Armamentarium zur Behandlung von Dyslipidämien und deren Folgen in die Hand zu geben.
Literatur
1.
Zurück zum Zitat Turley SD. Cholesterol metabolism and therapeutic targets: rationale for targeting multiple metabolic pathways. Clin Cardiol. 2004;27(6 Suppl 3):16–21.CrossRef Turley SD. Cholesterol metabolism and therapeutic targets: rationale for targeting multiple metabolic pathways. Clin Cardiol. 2004;27(6 Suppl 3):16–21.CrossRef
2.
Zurück zum Zitat Dietschy JM. Regulation of cholesterol metabolism in man and in other species. Klin Wochenschr. 1984;62(8):338–45.CrossRefPubMed Dietschy JM. Regulation of cholesterol metabolism in man and in other species. Klin Wochenschr. 1984;62(8):338–45.CrossRefPubMed
3.
Zurück zum Zitat Berg JM, Tymoczko JL, Stryer L. The complex regulation of cholesterol biosynthesis takes place at several levels. In: Biochemistry, 5. Aufl. New York: W. H. Freeman; 2002. Berg JM, Tymoczko JL, Stryer L. The complex regulation of cholesterol biosynthesis takes place at several levels. In: Biochemistry, 5. Aufl. New York: W. H. Freeman; 2002.
4.
Zurück zum Zitat Björkhem I, Meaney S. Brain Cholesterol: Long Secret Life Behind a Barrier. Arterioscler Thromb Vasc Biol. 2004;24(5):806–15.CrossRefPubMed Björkhem I, Meaney S. Brain Cholesterol: Long Secret Life Behind a Barrier. Arterioscler Thromb Vasc Biol. 2004;24(5):806–15.CrossRefPubMed
5.
Zurück zum Zitat Cooper AD. Hepatic uptake of chylomicron remnants. J Lipid Res. 1997;38(11):2173–92.PubMed Cooper AD. Hepatic uptake of chylomicron remnants. J Lipid Res. 1997;38(11):2173–92.PubMed
6.
Zurück zum Zitat Gay R, Rothenburger A. Störungen des Lipoproteinstoffwechsels. In: Silbernagl S, Lang F (Hrsg.). Taschenatlas Pathophysiologie, 3. Aufl. Stuttgart: Thieme; 2009. Gay R, Rothenburger A. Störungen des Lipoproteinstoffwechsels. In: Silbernagl S, Lang F (Hrsg.). Taschenatlas Pathophysiologie, 3. Aufl. Stuttgart: Thieme; 2009.
7.
Zurück zum Zitat Kwan BC, Kronenberg F, Beddhu S, et al. Lipoprotein metabolism and lipid management in chronic kidney disease. J Am Soc Nephrol. 2007;18(4):1246–61.CrossRefPubMed Kwan BC, Kronenberg F, Beddhu S, et al. Lipoprotein metabolism and lipid management in chronic kidney disease. J Am Soc Nephrol. 2007;18(4):1246–61.CrossRefPubMed
8.
Zurück zum Zitat Qian YW, Schmidt RJ, Zhang Y, et al. Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis. J Lipid Res. 2007;48(7):1488–98.CrossRefPubMed Qian YW, Schmidt RJ, Zhang Y, et al. Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis. J Lipid Res. 2007;48(7):1488–98.CrossRefPubMed
9.
Zurück zum Zitat Horton JD, Cohen JC, Hobbs HH. PCSK9: a convertase that coordinates LDL catabolism. J Lipid Res. 2009;50(Suppl):172–7.CrossRef Horton JD, Cohen JC, Hobbs HH. PCSK9: a convertase that coordinates LDL catabolism. J Lipid Res. 2009;50(Suppl):172–7.CrossRef
10.
Zurück zum Zitat Zhang DW, Lagace TA, Garuti R, et al. Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat a of low density lipoprotein receptor decreases receptor recycling and increases degradation. J Biol Chem. 2007;282(25):18602–12.CrossRefPubMed Zhang DW, Lagace TA, Garuti R, et al. Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat a of low density lipoprotein receptor decreases receptor recycling and increases degradation. J Biol Chem. 2007;282(25):18602–12.CrossRefPubMed
11.
Zurück zum Zitat Hadi HA, Carr CS, al Suwaidi J. Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome. Vasc Health Risk Manag. 2005;1(3):183–98.PubMedPubMedCentral Hadi HA, Carr CS, al Suwaidi J. Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome. Vasc Health Risk Manag. 2005;1(3):183–98.PubMedPubMedCentral
12.
Zurück zum Zitat Lum H, Roebuck KA. Oxidant stress and endothelial cell dysfunction. Am J Physiol Cell Physiol. 2001;280(4):C719–41.CrossRefPubMed Lum H, Roebuck KA. Oxidant stress and endothelial cell dysfunction. Am J Physiol Cell Physiol. 2001;280(4):C719–41.CrossRefPubMed
13.
Zurück zum Zitat Ferrieres J. Effects on coronary atherosclerosis by targeting low-density lipoprotein cholesterol with statins. Am J Cardiovasc Drugs. 2009;9(2):109–15.CrossRefPubMed Ferrieres J. Effects on coronary atherosclerosis by targeting low-density lipoprotein cholesterol with statins. Am J Cardiovasc Drugs. 2009;9(2):109–15.CrossRefPubMed
14.
Zurück zum Zitat Masumoto A, Hirooka Y, Hironaga K, et al. Effect of pravastatin on endothelial function in patients with coronary artery disease (cholesterol-independent effect of pravastatin). Am J Cardiol. 2001;88(11):1291–4.CrossRefPubMed Masumoto A, Hirooka Y, Hironaga K, et al. Effect of pravastatin on endothelial function in patients with coronary artery disease (cholesterol-independent effect of pravastatin). Am J Cardiol. 2001;88(11):1291–4.CrossRefPubMed
15.
Zurück zum Zitat Hu FB, Willett WC. Optimal diets for prevention of coronary heart disease. JAMA. 2002;288(20):2569–78.CrossRefPubMed Hu FB, Willett WC. Optimal diets for prevention of coronary heart disease. JAMA. 2002;288(20):2569–78.CrossRefPubMed
16.
Zurück zum Zitat Kato H, Tillotson J, Nichaman MZ, et al. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California. Am J Epidemiol. 1973;97(6):372–85.CrossRefPubMed Kato H, Tillotson J, Nichaman MZ, et al. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California. Am J Epidemiol. 1973;97(6):372–85.CrossRefPubMed
17.
Zurück zum Zitat Kromhout D, Menotti A, Bloemberg B, et al. Dietary saturated and trans fatty acids and cholesterol and 25-year mortality from coronary heart disease: the Seven Countries Study. Prev Med. 1995;24(3):308–15.CrossRefPubMed Kromhout D, Menotti A, Bloemberg B, et al. Dietary saturated and trans fatty acids and cholesterol and 25-year mortality from coronary heart disease: the Seven Countries Study. Prev Med. 1995;24(3):308–15.CrossRefPubMed
18.
Zurück zum Zitat Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4 S). Lancet. 1994;344(8934):1383–9. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4 S). Lancet. 1994;344(8934):1383–9.
19.
Zurück zum Zitat The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339(19):1349–57.CrossRef The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339(19):1349–57.CrossRef
20.
Zurück zum Zitat Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7–22.CrossRef Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7–22.CrossRef
21.
Zurück zum Zitat Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350(15):1495–504.CrossRefPubMed Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350(15):1495–504.CrossRefPubMed
22.
Zurück zum Zitat la Rosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352(14):1425–35.CrossRef la Rosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352(14):1425–35.CrossRef
23.
Zurück zum Zitat Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335(14):1001–9.CrossRefPubMed Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335(14):1001–9.CrossRefPubMed
24.
Zurück zum Zitat Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267–78.CrossRefPubMed Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267–78.CrossRefPubMed
25.
Zurück zum Zitat Cholesterol Treatment Trialists C, Fulcher J, O’Connell R, et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet. 2015;385(9976):1397–405.CrossRef Cholesterol Treatment Trialists C, Fulcher J, O’Connell R, et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet. 2015;385(9976):1397–405.CrossRef
26.
Zurück zum Zitat Cholesterol Treatment Trialists C, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670–81.CrossRef Cholesterol Treatment Trialists C, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670–81.CrossRef
27.
Zurück zum Zitat Cholesterol Treatment Trialists C, Kearney, Blackwell L, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371(9607):117–25.CrossRef Cholesterol Treatment Trialists C, Kearney, Blackwell L, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371(9607):117–25.CrossRef
28.
Zurück zum Zitat Cholesterol Treatment Trialists C, Mihaylova B, Emberson J, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380(9841):581–90.CrossRef Cholesterol Treatment Trialists C, Mihaylova B, Emberson J, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380(9841):581–90.CrossRef
30.
Zurück zum Zitat Hsia J, MacFadyen JG, Monyak J, et al. Cardiovascular event reduction and adverse events among subjects attaining low-density lipoprotein cholesterol 〈50 mg/dl with rosuvastatin. The JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin). J Am Coll Cardiol. 2011;57(16):1666–75.CrossRefPubMed Hsia J, MacFadyen JG, Monyak J, et al. Cardiovascular event reduction and adverse events among subjects attaining low-density lipoprotein cholesterol 〈50 mg/dl with rosuvastatin. The JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin). J Am Coll Cardiol. 2011;57(16):1666–75.CrossRefPubMed
31.
Zurück zum Zitat Wiviott SD, Cannon CP, Morrow DA, et al. Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Cardiol. 2005;46(8):1411–6.CrossRefPubMed Wiviott SD, Cannon CP, Morrow DA, et al. Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Cardiol. 2005;46(8):1411–6.CrossRefPubMed
32.
Zurück zum Zitat Giugliano RP, Wiviott SD, Blazing MA, et al. Safety and efficacy of long-term very low achieved LDL-C in the IMPROVE-IT trial. Eur Heart J. 2015;36(abstract supplement):2–68. Giugliano RP, Wiviott SD, Blazing MA, et al. Safety and efficacy of long-term very low achieved LDL-C in the IMPROVE-IT trial. Eur Heart J. 2015;36(abstract supplement):2–68.
33.
Zurück zum Zitat Bangalore S, Breazna A, DeMicco DA, et al. Visit-to-visit low-density lipoprotein cholesterol variability and risk of cardiovascular outcomes: insights from the TNT trial. J Am Coll Cardiol. 2015;65(15):1539–48.CrossRefPubMed Bangalore S, Breazna A, DeMicco DA, et al. Visit-to-visit low-density lipoprotein cholesterol variability and risk of cardiovascular outcomes: insights from the TNT trial. J Am Coll Cardiol. 2015;65(15):1539–48.CrossRefPubMed
34.
Zurück zum Zitat de Vera MA, Bhole V, Burns LC, et al. Impact of statin adherence on cardiovascular disease and mortality outcomes: a systematic review. Br J Clin Pharmacol. 2014;78(4):684–98.CrossRefPubMedPubMedCentral de Vera MA, Bhole V, Burns LC, et al. Impact of statin adherence on cardiovascular disease and mortality outcomes: a systematic review. Br J Clin Pharmacol. 2014;78(4):684–98.CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Ford I, Murray H, Packard CJ, et al. Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med. 2007;357(15):1477–86.CrossRefPubMed Ford I, Murray H, Packard CJ, et al. Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med. 2007;357(15):1477–86.CrossRefPubMed
37.
Zurück zum Zitat Ference BA, Yoo W, Alesh I, et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am Coll Cardiol. 2012;60(25):2631–9.CrossRefPubMed Ference BA, Yoo W, Alesh I, et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am Coll Cardiol. 2012;60(25):2631–9.CrossRefPubMed
38.
Zurück zum Zitat Myocardial Infarction Genetics Consortium I, Stitziel NO, Won HH, et al. Inactivating mutations in NPC1L1 and protection from coronary heart disease. N Engl J Med. 2014;371(22):2072–82.CrossRef Myocardial Infarction Genetics Consortium I, Stitziel NO, Won HH, et al. Inactivating mutations in NPC1L1 and protection from coronary heart disease. N Engl J Med. 2014;371(22):2072–82.CrossRef
39.
Zurück zum Zitat Poirier S, Mayer G. The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol. Drug Des Devel Ther. 2013;7:1135–48.PubMedPubMedCentral Poirier S, Mayer G. The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol. Drug Des Devel Ther. 2013;7:1135–48.PubMedPubMedCentral
40.
Zurück zum Zitat Kathiresan S, Melander O, Guiducci C, et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet. 2008;40(2):189–97.CrossRefPubMedPubMedCentral Kathiresan S, Melander O, Guiducci C, et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet. 2008;40(2):189–97.CrossRefPubMedPubMedCentral
41.
Zurück zum Zitat Kathiresan S, Myocardial Infarction Genetics C. A PCSK9 missense variant associated with a reduced risk of early-onset myocardial infarction. N Engl J Med. 2008;358(21):2299–300.CrossRefPubMed Kathiresan S, Myocardial Infarction Genetics C. A PCSK9 missense variant associated with a reduced risk of early-onset myocardial infarction. N Engl J Med. 2008;358(21):2299–300.CrossRefPubMed
42.
Zurück zum Zitat Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478–3490a.CrossRefPubMedPubMedCentral Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478–3490a.CrossRefPubMedPubMedCentral
43.
Zurück zum Zitat Huijgen R, Hutten BA, Kindt I, et al. Discriminative ability of LDL-cholesterol to identify patients with familial hypercholesterolemia: a cross-sectional study in 26,406 individuals tested for genetic FH. Circ Cardiovasc Genet. 2012;5(3):354–9.CrossRefPubMed Huijgen R, Hutten BA, Kindt I, et al. Discriminative ability of LDL-cholesterol to identify patients with familial hypercholesterolemia: a cross-sectional study in 26,406 individuals tested for genetic FH. Circ Cardiovasc Genet. 2012;5(3):354–9.CrossRefPubMed
44.
Zurück zum Zitat Starr B, Hadfield SG, Hutten BA, et al. Development of sensitive and specific age- and gender-specific low-density lipoprotein cholesterol cutoffs for diagnosis of first-degree relatives with familial hypercholesterolaemia in cascade testing. Clin Chem Lab Med. 2008;46(6):791–803.CrossRefPubMed Starr B, Hadfield SG, Hutten BA, et al. Development of sensitive and specific age- and gender-specific low-density lipoprotein cholesterol cutoffs for diagnosis of first-degree relatives with familial hypercholesterolaemia in cascade testing. Clin Chem Lab Med. 2008;46(6):791–803.CrossRefPubMed
45.
Zurück zum Zitat Vuorio A, Docherty KF, Humphries SE, et al. Statin treatment of children with familial hypercholesterolemia – trying to balance incomplete evidence of long-term safety and clinical accountability: are we approaching a consensus? Atherosclerosis. 2013;226(2):315–20.CrossRefPubMed Vuorio A, Docherty KF, Humphries SE, et al. Statin treatment of children with familial hypercholesterolemia – trying to balance incomplete evidence of long-term safety and clinical accountability: are we approaching a consensus? Atherosclerosis. 2013;226(2):315–20.CrossRefPubMed
46.
Zurück zum Zitat Catapano AL, Reiner Z, de Backer G, et al. 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). Atherosclerosis. 2011;217(1):3–46.CrossRefPubMed Catapano AL, Reiner Z, de Backer G, et al. 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). Atherosclerosis. 2011;217(1):3–46.CrossRefPubMed
47.
Zurück zum Zitat Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006;295(13):1556–65.CrossRefPubMed Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006;295(13):1556–65.CrossRefPubMed
48.
Zurück zum Zitat Nissen SE, Tuzcu EM, Schoenhagen P, et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA. 2004;291(9):1071–80.CrossRefPubMed Nissen SE, Tuzcu EM, Schoenhagen P, et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA. 2004;291(9):1071–80.CrossRefPubMed
49.
Zurück zum Zitat Tardif JC, Gregoire J, L’Allier PL, et al. Effects of the acyl coenzyme A: cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions. Circulation. 2004;110(21):3372–7.CrossRefPubMed Tardif JC, Gregoire J, L’Allier PL, et al. Effects of the acyl coenzyme A: cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions. Circulation. 2004;110(21):3372–7.CrossRefPubMed
50.
Zurück zum Zitat Nissen SE, Tuzcu EM, Libby P, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA. 2004;292(18):2217–25.CrossRefPubMed Nissen SE, Tuzcu EM, Libby P, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA. 2004;292(18):2217–25.CrossRefPubMed
51.
Zurück zum Zitat Sipahi I, Nicholls SJ, Tuzcu EM, et al. Coronary atherosclerosis can regress with very intensive statin therapy. Cleve Clin J Med. 2006;73(10):937–44.CrossRefPubMed Sipahi I, Nicholls SJ, Tuzcu EM, et al. Coronary atherosclerosis can regress with very intensive statin therapy. Cleve Clin J Med. 2006;73(10):937–44.CrossRefPubMed
52.
Zurück zum Zitat Nissen SE, Tuzcu EM, Brewer HB, et al. Effect of ACAT inhibition on the progression of coronary atherosclerosis. N Engl J Med. 2006;354(12):1253–63.CrossRefPubMed Nissen SE, Tuzcu EM, Brewer HB, et al. Effect of ACAT inhibition on the progression of coronary atherosclerosis. N Engl J Med. 2006;354(12):1253–63.CrossRefPubMed
53.
Zurück zum Zitat Gao WQ, Feng QZ, Li YF, et al. Systematic study of the effects of lowering low-density lipoprotein-cholesterol on regression of coronary atherosclerotic plaques using intravascular ultrasound. BMC Cardiovasc Disord. 2014;14:60.CrossRefPubMedPubMedCentral Gao WQ, Feng QZ, Li YF, et al. Systematic study of the effects of lowering low-density lipoprotein-cholesterol on regression of coronary atherosclerotic plaques using intravascular ultrasound. BMC Cardiovasc Disord. 2014;14:60.CrossRefPubMedPubMedCentral
54.
Zurück zum Zitat Nicholls SJ, Tuzcu EM, Sipahi I, et al. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA. 2007;297(5):499–508.CrossRefPubMed Nicholls SJ, Tuzcu EM, Sipahi I, et al. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA. 2007;297(5):499–508.CrossRefPubMed
55.
Zurück zum Zitat Kataoka Y, Hammadah M, Puri R, et al. Plaque microstructures in patients with coronary artery disease who achieved very low low-density lipoprotein cholesterol levels. Atherosclerosis. 2015;242(2):490–5.CrossRefPubMed Kataoka Y, Hammadah M, Puri R, et al. Plaque microstructures in patients with coronary artery disease who achieved very low low-density lipoprotein cholesterol levels. Atherosclerosis. 2015;242(2):490–5.CrossRefPubMed
56.
Zurück zum Zitat Puato M, Zambon A, Faggin E, et al. Statin treatment and carotid plaque composition: a review of clinical studies. Curr Vasc Pharmacol. 2014;12(3):518–26.CrossRefPubMed Puato M, Zambon A, Faggin E, et al. Statin treatment and carotid plaque composition: a review of clinical studies. Curr Vasc Pharmacol. 2014;12(3):518–26.CrossRefPubMed
57.
Zurück zum Zitat Puri R, Nissen SE, Somaratne R, et al. Impact of PCSK9 inhibition on coronary atheroma progression: rationale and design of GLAGOV (global assessment of plaque regression with a PCSK9 antibody as measured by Intravascular ultrasound). Am Heart J. 2016;176 doi:10.1016/j.ahj.2016.01.019.PubMed Puri R, Nissen SE, Somaratne R, et al. Impact of PCSK9 inhibition on coronary atheroma progression: rationale and design of GLAGOV (global assessment of plaque regression with a PCSK9 antibody as measured by Intravascular ultrasound). Am Heart J. 2016;176 doi:10.​1016/​j.​ahj.​2016.​01.​019.PubMed
58.
Zurück zum Zitat Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1500–9.CrossRefPubMed Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1500–9.CrossRefPubMed
59.
Zurück zum Zitat Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–97.CrossRefPubMed Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–97.CrossRefPubMed
60.
61.
Zurück zum Zitat Catapano AL, Ference BA. IMPROVE-IT and genetics reaffirm the causal role of LDL in cardiovascular disease. Atherosclerosis. 2015;241(2):498–501.CrossRefPubMed Catapano AL, Ference BA. IMPROVE-IT and genetics reaffirm the causal role of LDL in cardiovascular disease. Atherosclerosis. 2015;241(2):498–501.CrossRefPubMed
62.
Zurück zum Zitat Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1489–99.CrossRefPubMed Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1489–99.CrossRefPubMed
63.
Zurück zum Zitat la Rosa JC, Grundy SM, Kastelein JJ, et al. Safety and efficacy of atorvastatin-induced very low-density lipoprotein cholesterol levels in patients with coronary heart disease (a post hoc analysis of the treating to new targets [TNT] study). Am J Cardiol. 2007;100(5):747–52.CrossRef la Rosa JC, Grundy SM, Kastelein JJ, et al. Safety and efficacy of atorvastatin-induced very low-density lipoprotein cholesterol levels in patients with coronary heart disease (a post hoc analysis of the treating to new targets [TNT] study). Am J Cardiol. 2007;100(5):747–52.CrossRef
65.
Zurück zum Zitat Zhao Z, Tuakli-Wosornu Y, Lagace TA, et al. Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am J Hum Genet. 2006;79(3):514–23.CrossRefPubMedPubMedCentral Zhao Z, Tuakli-Wosornu Y, Lagace TA, et al. Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am J Hum Genet. 2006;79(3):514–23.CrossRefPubMedPubMedCentral
66.
Zurück zum Zitat Cohen JC, Boerwinkle E, Mosley TH Jr., et al. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354(12):1264–72.CrossRefPubMed Cohen JC, Boerwinkle E, Mosley TH Jr., et al. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354(12):1264–72.CrossRefPubMed
67.
68.
Zurück zum Zitat Abifadel M, Rabes JP, Devillers M, et al. Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease. Hum Mutat. 2009;30(4):520–9.CrossRefPubMed Abifadel M, Rabes JP, Devillers M, et al. Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease. Hum Mutat. 2009;30(4):520–9.CrossRefPubMed
69.
Zurück zum Zitat Lakoski SG, Lagace TA, Cohen JC, et al. Genetic and metabolic determinants of plasma PCSK9 levels. J Clin Endocrinol Metab. 2009;94(7):2537–43.CrossRefPubMedPubMedCentral Lakoski SG, Lagace TA, Cohen JC, et al. Genetic and metabolic determinants of plasma PCSK9 levels. J Clin Endocrinol Metab. 2009;94(7):2537–43.CrossRefPubMedPubMedCentral
70.
Zurück zum Zitat Benn M, Nordestgaard BG, Grande P, et al. PCSK9 R46L, low-density lipoprotein cholesterol levels, and risk of ischemic heart disease: 3 independent studies and meta-analyses. J Am Coll Cardiol. 2010;55(25):2833–42.CrossRefPubMed Benn M, Nordestgaard BG, Grande P, et al. PCSK9 R46L, low-density lipoprotein cholesterol levels, and risk of ischemic heart disease: 3 independent studies and meta-analyses. J Am Coll Cardiol. 2010;55(25):2833–42.CrossRefPubMed
71.
Zurück zum Zitat Cunningham D, Danley DE, Geoghegan KF, et al. Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia. Nat Struct Mol Biol. 2007;14(5):413–9.CrossRefPubMed Cunningham D, Danley DE, Geoghegan KF, et al. Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia. Nat Struct Mol Biol. 2007;14(5):413–9.CrossRefPubMed
72.
Zurück zum Zitat Mayne J, Dewpura T, Raymond A, et al. Novel loss-of-function PCSK9 variant is associated with low plasma LDL cholesterol in a French-Canadian family and with impaired processing and secretion in cell culture. Clin Chem. 2011;57(10):1415–23.CrossRefPubMed Mayne J, Dewpura T, Raymond A, et al. Novel loss-of-function PCSK9 variant is associated with low plasma LDL cholesterol in a French-Canadian family and with impaired processing and secretion in cell culture. Clin Chem. 2011;57(10):1415–23.CrossRefPubMed
73.
Zurück zum Zitat Kotowski IK, Pertsemlidis A, Luke A, et al. A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol. Am J Hum Genet. 2006;78(3):410–22.CrossRefPubMedPubMedCentral Kotowski IK, Pertsemlidis A, Luke A, et al. A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol. Am J Hum Genet. 2006;78(3):410–22.CrossRefPubMedPubMedCentral
74.
Zurück zum Zitat Tibolla G, Norata GD, Artali R, et al. Proprotein convertase subtilisin/kexin type 9 (PCSK9): from structure-function relation to therapeutic inhibition. Nutrition, metabolism, and cardiovascular diseases. Nutr Metab Cardiovasc Dis. 2011;21(11):835–43.CrossRefPubMed Tibolla G, Norata GD, Artali R, et al. Proprotein convertase subtilisin/kexin type 9 (PCSK9): from structure-function relation to therapeutic inhibition. Nutrition, metabolism, and cardiovascular diseases. Nutr Metab Cardiovasc Dis. 2011;21(11):835–43.CrossRefPubMed
75.
Zurück zum Zitat Collins R, Armitage J, Parish S, et al. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361(9374):2005–16.CrossRefPubMed Collins R, Armitage J, Parish S, et al. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361(9374):2005–16.CrossRefPubMed
76.
Zurück zum Zitat Ahmed S, Cannon CP, Murphy SA, et al. Acute coronary syndromes and diabetes: Is intensive lipid lowering beneficial? Results of the PROVE IT-TIMI 22 trial. Eur Heart J. 2006;27(19):2323–9.CrossRefPubMed Ahmed S, Cannon CP, Murphy SA, et al. Acute coronary syndromes and diabetes: Is intensive lipid lowering beneficial? Results of the PROVE IT-TIMI 22 trial. Eur Heart J. 2006;27(19):2323–9.CrossRefPubMed
77.
Zurück zum Zitat Sattar N, Preiss D, Robinson JG, et al. Lipid-lowering efficacy of the PCSK9 inhibitor evolocumab (AMG 145) in patients with type 2 diabetes: a meta-analysis of individual patient data. Lancet Diabetes Endocrinol. 2016;4(5):403–10.CrossRef Sattar N, Preiss D, Robinson JG, et al. Lipid-lowering efficacy of the PCSK9 inhibitor evolocumab (AMG 145) in patients with type 2 diabetes: a meta-analysis of individual patient data. Lancet Diabetes Endocrinol. 2016;4(5):403–10.CrossRef
78.
Zurück zum Zitat Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015;372(25):2387–97 (supplementary material, page 41). Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015;372(25):2387–97 (supplementary material, page 41).
79.
Zurück zum Zitat Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735–42.CrossRefPubMed Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735–42.CrossRefPubMed
80.
Zurück zum Zitat Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011;305(24):2556–64.CrossRefPubMed Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011;305(24):2556–64.CrossRefPubMed
81.
Zurück zum Zitat Sabatine MS, Giugliano RP, Keech A, et al. Rationale and design of the further cardiovascular outcomes research with PCSK9 inhibition in subjects with elevated risk trial. Am Heart J. 2016;173:94–101.CrossRefPubMed Sabatine MS, Giugliano RP, Keech A, et al. Rationale and design of the further cardiovascular outcomes research with PCSK9 inhibition in subjects with elevated risk trial. Am Heart J. 2016;173:94–101.CrossRefPubMed
82.
Zurück zum Zitat Reiner Z, De Backer G, Fras Z, et al. Lipid lowering drug therapy in patients with coronary heart disease from 24 European countries – findings from the EUROASPIRE IV survey. Atherosclerosis. 2016;246:243–50.CrossRefPubMed Reiner Z, De Backer G, Fras Z, et al. Lipid lowering drug therapy in patients with coronary heart disease from 24 European countries – findings from the EUROASPIRE IV survey. Atherosclerosis. 2016;246:243–50.CrossRefPubMed
83.
Zurück zum Zitat Nicholls SJ, Lincoff A, Barter P, et al, Late-Breaking Clinical Trials II. The ACCELERATE trial: impact of the cholesteryl ester transfer protein inhibitor evacetrapib on cardiovascular outcome. 65th Annual Scientific Session and Expo of the American College of Cardiology, Chicago. 2016. Nicholls SJ, Lincoff A, Barter P, et al, Late-Breaking Clinical Trials II. The ACCELERATE trial: impact of the cholesteryl ester transfer protein inhibitor evacetrapib on cardiovascular outcome. 65th Annual Scientific Session and Expo of the American College of Cardiology, Chicago. 2016.
84.
Zurück zum Zitat 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(21):2109–22.CrossRefPubMed 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(21):2109–22.CrossRefPubMed
85.
Zurück zum Zitat 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(22):2089–99.CrossRefPubMed 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(22):2089–99.CrossRefPubMed
88.
Zurück zum Zitat Besseling J, van Capelleveen J, Kastelein JJ, et al. LDL cholesterol goals in high-risk patients: how low do we go and how do we get there? Drugs. 2013;73(4):293–301.CrossRefPubMed Besseling J, van Capelleveen J, Kastelein JJ, et al. LDL cholesterol goals in high-risk patients: how low do we go and how do we get there? Drugs. 2013;73(4):293–301.CrossRefPubMed
89.
Metadaten
Titel
LDL-Cholesterin und kardiovaskuläre Ereignisse: je niedriger desto besser?
verfasst von
Prim. Univ.-Doz. Dr. Raimund Weitgasser
Dr. Michaela Ratzinger
Dr. Margit Hemetsberger
Prim. Univ. Prof. Dr. Peter Siostrzonek
Publikationsdatum
21.10.2016
Verlag
Springer Vienna
Erschienen in
Wiener Medizinische Wochenschrift / Ausgabe 5-6/2018
Print ISSN: 0043-5341
Elektronische ISSN: 1563-258X
DOI
https://doi.org/10.1007/s10354-016-0518-2

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