Download PDF
Kardiologie up2date 2011; 7(4): 257-268
DOI: 10.1055/s-0030-1257051
Hotline – Koronare Herzerkrankung und Atherosklerose

© Georg Thieme Verlag KG Stuttgart · New York

Antiatherogene Wirkung von High-Density-Lipoproteinen

Katherine  Sattler, Bodo  Levkau
Further Information

Publication History

Publication Date:
02 February 2012 (online)

Also available at
    Permissions and Reprints All articles of this category

Abstract

The heterogeneous plasma fraction of HDL-cholesterol (HDL-C) is the most important „endogenous negative“ risk factor for coronary artery disease. Although the primary target for therapy remains the reduction of LDL-C, HDL-C raising strategies may offer additional benefit. While prospective clinical studies are under way to test this issue, new pharmaceutical agents are currently being developed to effectively increase plasma HDL-C or improve HDL function. In this review, we discuss the latest developments in the field.

Literatur

  • 1 di Angelantonio E, Sarwar N, Perry P et al. Major lipids, apolipoproteins, and risk of vascular disease.  Jama. 2009;  302 1993-2000
    Google Scholar
  • 2 Baigent C, Blackwell L, Emberson J 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. ;  376 1670-1681
    Google Scholar
  • 3 Chapman M J, Ginsberg H N, Amarenco P et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management.  Eur Heart J. 2011;  32 1345-1361
    Google Scholar
  • 4 Rosenson R S, Brewer  Jr. H B, Chapman M J et al. HDL Measures, Particle Heterogeneity, Proposed Nomenclature, and Relation to Atherosclerotic Cardiovascular Events.  Clin Chem. 2011;  57 392-410
    Google Scholar
  • 5 von Eckardstein A, Hersberger M, Rohrer L. Current understanding of the metabolism and biological actions of HDL.  Curr Opin Clin Nutr Metab Care. 2005;  8 147-152
    Google Scholar
  • 6 Kontush A, Chapman M J. Antiatherogenic small, dense HDL--guardian angel of the arterial wall?.  Nat Clin Pract Cardiovasc Med. 2006;  3 144-153
    Google Scholar
  • 7 Oram J F, Vaughan A M. ATP-Binding cassette cholesterol transporters and cardiovascular disease.  Circ Res. 2006;  99 1031-1043
    Google Scholar
  • 8 de la Llera-Moya M, Drazul-Schrader D, Asztalos B F et al. The ability to promote efflux via ABCA1 determines the capacity of serum specimens with similar high-density lipoprotein cholesterol to remove cholesterol from macrophages.  Arterioscler Thromb Vasc Biol. ;  30 796-801
    Google Scholar
  • 9 van Dam M J, de Groot E, Clee S M et al. Association between increased arterial-wall thickness and impairment in ABCA1-driven cholesterol efflux: an observational study.  Lancet. 2002;  359 37-42
    Google Scholar
  • 10 Shaw J A, Bobik A, Murphy A et al. Infusion of reconstituted high-density lipoprotein leads to acute changes in human atherosclerotic plaque.  Circ Res. 2008;  103 1084-1091
    Google Scholar
  • 11 Yuhanna I S, Zhu Y, Cox B E et al. High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase.  Nat Med. 2001;  7 853-857
    Google Scholar
  • 12 Nofer J R, van der Giet M, Tolle M et al. HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3.  J Clin Invest. 2004;  113 569-581
    Google Scholar
  • 13 Kuvin J T, Patel A R, Sidhu M et al. Relation between high-density lipoprotein cholesterol and peripheral vasomotor function.  Am J Cardiol. 2003;  92 275-279
    Google Scholar
  • 14 Spieker L E, Sudano I, Hurlimann D et al. High-density lipoprotein restores endothelial function in hypercholesterolemic men.  Circulation. 2002;  105 1399-1402
    Google Scholar
  • 15 Mackness M I, Arrol S, Abbott C et al. Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase.  Atherosclerosis. 1993;  104 129-135
    Google Scholar
  • 16 Miura S, Fujino M, Matsuo Y et al. High density lipoprotein-induced angiogenesis requires the activation of Ras/MAP kinase in human coronary artery endothelial cells.  Arterioscler Thromb Vasc Biol. 2003;  23 802-808
    Google Scholar
  • 17 Barter P J. Inhibition of endothelial cell adhesion molecule expression by high density lipoproteins.  Clin Exp Pharmacol Physiol. 1997;  24 286-287
    Google Scholar
  • 18 Tolle M, Pawlak A, Schuchardt M et al. HDL-associated lysosphingolipids inhibit NAD(P)H oxidase-dependent monocyte chemoattractant protein-1 production.  Arterioscler Thromb Vasc Biol. 2008;  28 1542-1548
    Google Scholar
  • 19 Gharavi N M, Gargalovic P S, Chang I et al. High-density lipoprotein modulates oxidized phospholipid signaling in human endothelial cells from proinflammatory to anti-inflammatory.  Arterioscler Thromb Vasc Biol. 2007;  27 1346-1353
    Google Scholar
  • 20 Levkau B, Hermann S, Theilmeier G et al. High-density lipoprotein stimulates myocardial perfusion in vivo.  Circulation. 2004;  110 3355-3359
    Google Scholar
  • 21 Theilmeier G, Schmidt C, Herrmann J et al. High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor.  Circulation. 2006;  114 1403-1409
    Google Scholar
  • 22 Khera A V, Cuchel M, de la Llera-Moya M et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis.  N Engl J Med. ;  364 127-135
    Google Scholar
  • 23 Nobecourt E, Jacqueminet S, Hansel B et al. Defective antioxidative activity of small dense HDL3 particles in type 2 diabetes: relationship to elevated oxidative stress and hyperglycaemia.  Diabetologia. 2005;  48 529-538
    Google Scholar
  • 24 Ansell B J, Navab M, Hama S et al. Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment.  Circulation. 2003;  108 2751-2756
    Google Scholar
  • 25 Besler C, Heinrich K, Rohrer L et al. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease.  J Clin Invest. ;  121 2693-2708
    Google Scholar
  • 26 Vaisar T, Pennathur S, Green P S et al. Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL.  J Clin Invest. 2007;  117 746-756
    Google Scholar
  • 27 Pruzanski W, Stefanski E, de Beer F C et al. Comparative analysis of lipid composition of normal and acute-phase high density lipoproteins.  J Lipid Res. 2000;  41 1035-1047
    Google Scholar
  • 28 Bakogianni M C, Kalofoutis C A, Skenderi K I et al. Clinical evaluation of plasma high-density lipoprotein subfractions (HDL2, HDL3) in non-insulin-dependent diabetics with coronary artery disease.  J Diabetes Complications. 2001;  15 265-269
    Google Scholar
  • 29 Cheung M C, Brown B G, Wolf A C et al. Altered particle size distribution of apolipoprotein A-I-containing lipoproteins in subjects with coronary artery disease.  J Lipid Res. 1991;  32 383-394
    Google Scholar
  • 30 Zheng L, Nukuna B, Brennan M L et al. Apolipoprotein A-I is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subjects with cardiovascular disease.  J Clin Invest. 2004;  114 529-541
    Google Scholar
  • 31 Sattler K J, Elbasan S, Keul P et al. Sphingosine 1-phosphate levels in plasma and HDL are altered in coronary artery disease.  Basic Res Cardiol. ;  105 821-832
    Google Scholar
  • 32 Wilson P W, D'Agostino R B, Levy D et al. Prediction of coronary heart disease using risk factor categories.  Circulation. 1998;  97 1837-1847
    Google Scholar
  • 33 Assmann G, Cullen P, Schulte H. Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Munster (PROCAM) study.  Circulation. 2002;  105 310-315
    Google Scholar
  • 34 Thomsen T F, Davidsen M, Ibsen H et al. A new method for CHD prediction and prevention based on regional risk scores and randomized clinical trials; PRECARD and the Copenhagen Risk Score.  J Cardiovasc Risk. 2001;  8 291-297
    Google Scholar
  • 35 Tunstall-Pedoe H, Woodward M. By neglecting deprivation, cardiovascular risk scoring will exacerbate social gradients in disease.  Heart. 2006;  92 307-310
    Google Scholar
  • 36 Graham I, Atar D, Borch-Johnsen K et al. European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Fourth 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).  Eur J Cardiovasc Prev Rehabil. 2007;  14 (Suppl 2) 1-40
    Google Scholar
  • 37 Gordon T, Castelli W P, Hjortland M C et al. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study.  Am J Med. 1977;  62 707-714
    Google Scholar
  • 38 Sharrett A R, Ballantyne C M, Coady S A et al. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study.  Circulation. 2001;  104 1108-1113
    Google Scholar
  • 39 Pletcher M J, Bibbins-Domingo K, Liu K et al. Nonoptimal lipids commonly present in young adults and coronary calcium later in life: the CARDIA (Coronary Artery Risk Development in Young Adults) study.  Ann Intern Med. ;  153 137-146
    Google Scholar
  • 40 Castelli W P, Doyle J T, Gordon T et al. HDL cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study.  Circulation. 1977;  55 767-772
    Google Scholar
  • 41 Alber H F, Wanitschek M M, de Waha S et al. High-density lipoprotein cholesterol, C-reactive protein, and prevalence and severity of coronary artery disease in 5641 consecutive patients undergoing coronary angiography.  Eur J Clin Invest. 2008;  38 372-380
    Google Scholar
  • 42 Gordon D J, Probstfield J L, Garrison R J et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies.  Circulation. 1989;  79 8-15
    Google Scholar
  • 43 Kreuzer J. Medikamentöse Therapie von Fettstoffwechselstörungen.  Arzneimitteltherapie. 2011;  29 13-22
    Google Scholar
  • 44 Neurologie DGf. Primär- und Sekundärprävention der zerebralen Ischämie. In: Diener H C, Putzki N Leitlinien für die Diagnostik und Therapie in der Neurologie. 4. überarb. Aufl. Stuttgart: Georg Thieme Verlag; 2008
    Google Scholar
  • 45 Böhner H, Balzer K, Nowak T. Leitlinie Medikamentöse Therapie. 2008. http://www.gefaesschirurgie.de/fileadmin/websites/dgg/download/LL_Medikamentoese_Therapie_2011.pdf.14.11.2011
    Google Scholar
  • 46 Drexel H, Amann F W, Rentsch K et al. Relation of the level of high-density lipoprotein subfractions to the presence and extent of coronary artery disease.  Am J Cardiol. 1992;  70 436-440
    Google Scholar
  • 47 Rossner S, Kjellin K G, Mettinger K L et al. Normal serum-cholesterol but low H.D.L.-cholesterol concentration in young patients with ischaemic cerebrovascular disease.  Lancet. 1978;  1 577-579
    Google Scholar
  • 48 Pauciullo P, Rubba P, Marotta G et al. Abnormalities in serum lipoprotein composition in patients with premature coronary heart disease compared to serum lipid matched controls.  Atherosclerosis. 1988;  73 241-246
    Google Scholar
  • 49 Jenkins P J, Harper R W, Nestel P J. Severity of coronary atherosclerosis related to lipoprotein concentration.  Br Med J. 1978;  2 388-391
    Google Scholar
  • 50 Phan B A, Chu B, Polissar N et al. Association of high-density lipoprotein levels and carotid atherosclerotic plaque characteristics by magnetic resonance imaging.  Int J Cardiovasc Imaging. 2007;  23 337-342
    Google Scholar
  • 51 Berge K G, Canner P L, Hainline A. High-density lipoprotein cholesterol and prognosis after myocardial infarction.  Circulation. 1982;  66 1176-1178
    Google Scholar
  • 52 Ghazzal Z B, Dhawan S S, Sheikh A et al. Usefulness of serum high-density lipoprotein cholesterol level as an independent predictor of one-year mortality after percutaneous coronary interventions.  Am J Cardiol. 2009;  103 902-906
    Google Scholar
  • 53 Amarenco P, Goldstein L B, Callahan A et al. Baseline blood pressure, low- and high-density lipoproteins, and triglycerides and the risk of vascular events in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.  Atherosclerosis. 2009;  204 515-520
    Google Scholar
  • 54 von Birgelen C, Hartmann M, Mintz G S et al. 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. 2003;  108 2757-2762
    Google Scholar
  • 55 Jafri H, Alsheikh-Ali A A, Karas R H. Meta-analysis: statin therapy does not alter the association between low levels of high-density lipoprotein cholesterol and increased cardiovascular risk.  Ann Intern Med. 2010;  153 800-808
    Google Scholar
  • 56 Wolfram R M, Brewer H B, Xue Z et al. Impact of low high-density lipoproteins on in-hospital events and one-year clinical outcomes in patients with non-ST-elevation myocardial infarction acute coronary syndrome treated with drug-eluting stent implantation.  Am J Cardiol. 2006;  98 711-717
    Google Scholar
  • 57 Sattler K J, Herrmann J, Yun S et al. High high-density lipoprotein-cholesterol reduces risk and extent of percutaneous coronary intervention-related myocardial infarction and improves long-term outcome in patients undergoing elective percutaneous coronary intervention.  Eur Heart J. 2009;  30 1894-1902
    Google Scholar
  • 58 Foody J M, Ferdinand F D, Pearce G L et al. HDL cholesterol level predicts survival in men after coronary artery bypass graft surgery: 20-year experience from The Cleveland Clinic Foundation.  Circulation. 2000;  102 III 90-94
    Google Scholar
  • 59 Barter P, Gotto A M, LaRosa J C et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events.  N Engl J Med. 2007;  357 1301-1310
    Google Scholar
  • 60 Ballantyne C M, Raichlen J S, Nicholls S J et al. Effect of rosuvastatin therapy on coronary artery stenoses assessed by quantitative coronary angiography: a study to evaluate the effect of rosuvastatin on intravascular ultrasound-derived coronary atheroma burden.  Circulation. 2008;  117 2458-2466
    Google Scholar
  • 61 Robins S J, Collins D, Wittes J T et al. Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial.  Jama. 2001;  285 1585-1591
    Google Scholar
  • 62 Villines T C, Stanek E J, Devine P J et al. The ARBITER 6-HALTS Trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies in Atherosclerosis): final results and the impact of medication adherence, dose, and treatment duration.  J Am Coll Cardiol. 2010;  55 2721-2726
    Google Scholar
  • 63 Fox K, Garcia M A, Ardissino D et al. Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology.  Eur Heart J. 2006;  27 1341-1381
    Google Scholar
  • 64 Poss J, Bohm M, Laufs U. HDL and CETP in atherogenesis.  Dtsch Med Wochenschr. 2010;  135 188-192
    Google Scholar
  • 65 Grover S A, Kaouache M, Joseph L et al. Evaluating the incremental benefits of raising high-density lipoprotein cholesterol levels during lipid therapy after adjustment for the reductions in other blood lipid levels.  Arch Intern Med. 2009;  169 1775-1780
    Google Scholar
  • 66 Goldenberg I, Benderly M, Sidi R et al. Relation of clinical benefit of raising high-density lipoprotein cholesterol to serum levels of low-density lipoprotein cholesterol in patients with coronary heart disease (from the Bezafibrate Infarction Prevention Trial).  Am J Cardiol. 2009;  103 41-45
    Google Scholar
  • 67 Durstine J L, Grandjean P W, Davis P G et al. Blood lipid and lipoprotein adaptations to exercise: a quantitative analysis.  Sports Med. 2001;  31 1033-1062
    Google Scholar
  • 68 Kiens B, Jorgensen I, Lewis S et al. Increased plasma HDL-cholesterol and apo A-1 in sedentary middle-aged men after physical conditioning.  Eur J Clin Invest. 1980;  10 203-209
    Google Scholar
  • 69 Dolgin E. Trial puts niacin-and cholesterol dogma-in the line of fire.  Nat Med. 2011;  17 756
    Google Scholar
  • 70 Alsheikh-Ali A A, Lin J L, Abourjaily P et al. Prevalence of low high-density lipoprotein cholesterol in patients with documented coronary heart disease or risk equivalent and controlled low-density lipoprotein cholesterol.  Am J Cardiol. 2007;  100 1499-1501
    Google Scholar
  • 71 Shepherd J, Packard C J, Patsch J R et al. Effects of nicotinic acid therapy on plasma high density lipoprotein subfraction distribution and composition and on apolipoprotein A metabolism.  J Clin Invest. 1979;  63 858-867
    Google Scholar
  • 72 Wu Z H, Zhao S P. Niacin promotes cholesterol efflux through stimulation of the PPARgamma-LXRalpha-ABCA1 pathway in 3T3-L1 adipocytes.  Pharmacology. 2009;  84 282-287
    Google Scholar
  • 73 Tunaru S, Kero J, Schaub A et al. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect.  Nat Med. 2003;  9 352-355
    Google Scholar
  • 74 Shepherd J, Betteridge J, Van Gaal L. Nicotinic acid in the management of dyslipidaemia associated with diabetes and metabolic syndrome: a position paper developed by a European Consensus Panel.  Curr Med Res Opin. 2005;  21 665-682
    Google Scholar
  • 75 Insull W, McGovern M E, Schrott H et al. Efficacy of extended-release niacin with lovastatin for hypercholesterolemia: assessing all reasonable doses with innovative surface graph analysis.  Arch Intern Med. 2004;  164 1121-1127
    Google Scholar
  • 76 Parhofer K G. Review of extended-release niacin/laropiprant fixed combination in the treatment of mixed dyslipidemia and primary hypercholesterolemia.  Vasc Health Risk Manag. 2009;  5 901-908
    Google Scholar
  • 77 Brown B G, Zhao X Q, Chait A et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease.  N Engl J Med. 2001;  345 1583-1592
    Google Scholar
  • 78 Taylor A J, Lee H J, Sullenberger L E. The effect of 24 months of combination statin and extended-release niacin on carotid intima-media thickness: ARBITER 3.  Curr Med Res Opin. 2006;  22 2243-2250
    Google Scholar
  • 79 Clofibrate and niacin in coronary heart disease.  Jama. 1975;  231 360-381
    Google Scholar
  • 80 Canner P L, Furberg C D, Terrin M L et al. Benefits of niacin by glycemic status in patients with healed myocardial infarction (from the Coronary Drug Project).  Am J Cardiol. 2005;  95 254-257
    Google Scholar
  • 81 Bruckert E, Labreuche J, Amarenco P. Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis.  Atherosclerosis. 2010;  210 353-361
    Google Scholar
  • 82 Wise J. Trial of niacin alongside statin is stopped early.  BMJ. 2011;  342 D3400
    Google Scholar
  • 83 Marx N, Duez H, Fruchart J C et al. Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells.  Circ Res. 2004;  94 1168-1178
    Google Scholar
  • 84 Lalloyer F, Staels B. Fibrates, glitazones, and peroxisome proliferator-activated receptors.  Arterioscler Thromb Vasc Biol. 2010;  30 894-899
    Google Scholar
  • 85 Manninen V, Tenkanen L, Koskinen P et al. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Implications for treatment.  Circulation. 1992;  85 37-45
    Google Scholar
  • 86 Sacks F M, Carey V J, Fruchart J C. Combination lipid therapy in type 2 diabetes.  N Engl J Med. 2010;  363 692-694 (author reply 694–695)
    Google Scholar
  • 87 Athyros V G, Papageorgiou A A, Athyrou V V et al. Atorvastatin and micronized fenofibrate alone and in combination in type 2 diabetes with combined hyperlipidemia.  Diabetes Care. 2002;  25 1198-1202
    Google Scholar
  • 88 Derosa G, Cicero A E, Bertone G et al. Comparison of fluvastatin + fenofibrate combination therapy and fluvastatin monotherapy in the treatment of combined hyperlipidemia, type 2 diabetes mellitus, and coronary heart disease: a 12-month, randomized, double-blind, controlled trial.  Clin Ther. 2004;  26 1599-1607
    Google Scholar
  • 89 Koh K K, Quon M J, Han S H et al. Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia.  J Am Coll Cardiol. 2005;  45 1649-1653
    Google Scholar
  • 90 Grundy S M, Vega G L, Yuan Z et al. Effectiveness and tolerability of simvastatin plus fenofibrate for combined hyperlipidemia (the SAFARI trial).  Am J Cardiol. 2005;  95 462-468
    Google Scholar
  • 91 Ginsberg H N, Elam M B, Lovato L C et al. Effects of combination lipid therapy in type 2 diabetes mellitus.  N Engl J Med. ;  362 1563-1574
    Google Scholar
  • 92 Dormandy J A, Charbonnel B, Eckland D J et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial.  Lancet. 2005;  366 1279-1289
    Google Scholar
  • 93 Nissen S E, Nicholls S J, Wolski K et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial.  Jama. 2008;  299 1561-1573
    Google Scholar
  • 94 Lincoff A M, Wolski K, Nicholls S J et al. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials.  Jama. 2007;  298 1180-1188
    Google Scholar
  • 95 Henry R R, Lincoff A M, Mudaliar S et al. Effect of the dual peroxisome proliferator-activated receptor-alpha/gamma agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): a phase II, randomised, dose-ranging study.  Lancet. 2009;  374 126-135
    Google Scholar
  • 96 deGoma E M, Leeper N J, Heidenreich P A. Clinical significance of high-density lipoprotein cholesterol in patients with low low-density lipoprotein cholesterol.  J Am Coll Cardiol. 2008;  51 49-55
    Google Scholar
  • 97 van der Steeg W A, Holme I, Boekholdt S M 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
    Google Scholar
  • 98 Asztalos B F, Horvath K V, McNamara J R et al. Comparing the effects of five different statins on the HDL subpopulation profiles of coronary heart disease patients.  Atherosclerosis. 2002;  164 361-369
    Google Scholar
  • 99 Asztalos B F, Collins D, Horvath K V et al. Relation of gemfibrozil treatment and high-density lipoprotein subpopulation profile with cardiovascular events in the Veterans Affairs High-Density Lipoprotein Intervention Trial.  Metabolism. 2008;  57 77-83
    Google Scholar
  • 100 Otvos J D, Collins D, Freedman D S et al. Low-density lipoprotein and high-density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial.  Circulation. 2006;  113 1556-1563
    Google Scholar
  • 101 Vasan R S, Pencina M J, Robins S J et al. Association of circulating cholesteryl ester transfer protein activity with incidence of cardiovascular disease in the community.  Circulation. 2009;  120 2414-2420
    Google Scholar
  • 102 Chapman M J, Le Goff W, Guerin M et al. Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors.  Eur Heart J. 2010;  31 149-164
    Google Scholar
  • 103 Barter P J, 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
    Google Scholar
  • 104 Hu X, Dietz J D, Xia C et al. Torcetrapib induces aldosterone and cortisol production by an intracellular calcium-mediated mechanism independently of cholesteryl ester transfer protein inhibition.  Endocrinology. 2009;  150 2211-2219
    Google Scholar
  • 105 Forrest M J, Bloomfield D, Briscoe R J et al. Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone.  Br J Pharmacol. 2008;  154 1465-1473
    Google Scholar
  • 106 Cannon C P, Shah S, Dansky H M et al. Safety of anacetrapib in patients with or at high risk for coronary heart disease.  N Engl J Med. 2010;  363 2406-2415
    Google Scholar
  • 107 Yvan-Charvet L, Kling J, Pagler T et al. Cholesterol efflux potential and antiinflammatory properties of high-density lipoprotein after treatment with niacin or anacetrapib.  Arterioscler Thromb Vasc Biol. 2010;  30 1430-1438
    Google Scholar
  • 108 Olsson A G, Schwartz G G, Szarek M et al. High-density lipoprotein, but not low-density lipoprotein cholesterol levels influence short-term prognosis after acute coronary syndrome: results from the MIRACL trial.  Eur Heart J. 2005;  26 890-896
    Google Scholar
  • 109 Tardif J C, Gregoire J, L"Allier P L et al. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial.  Jama. 2007;  297 1675-1682
    Google Scholar
  • 110 Nicholls S J, Tuzcu E M, Sipahi I et al. Relationship between atheroma regression and change in lumen size after infusion of apolipoprotein A-I Milano.  J Am Coll Cardiol. 2006;  47 992-997
    Google Scholar
  • 111 Nissen S E, Tsunoda T, Tuzcu E M et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial.  Jama. 2003;  290 2292-2300
    Google Scholar
  • 112 Patel S, Drew B G, Nakhla S et al. Reconstituted high-density lipoprotein increases plasma high-density lipoprotein anti-inflammatory properties and cholesterol efflux capacity in patients with type 2 diabetes.  J Am Coll Cardiol. 2009;  53 962-971
    Google Scholar
  • 113 Chenevard R, Hurlimann D, Spieker L et al. RESEARCH:Reconstituted HDL in Acute Coronary Syndromes.  Cardiovasc Ther. 2010;  DOI: doi: 10.1111/j.1755-5922.2010.00221.X. [Epub ahead of print]
    Google Scholar
  • 114 Navab M, Anantharamaiah G M, Reddy S T et al. Peptide Mimetics of Apolipoproteins Improve HDL Function.  J Clin Lipidol. 2007;  1 142-147
    Google Scholar
  • 115 D'Souza W, Stonik J A, Murphy A et al. Structure/function relationships of apolipoprotein a-I mimetic peptides: implications for antiatherogenic activities of high-density lipoprotein.  Circ Res. 2010;  107 217-227
    Google Scholar
  • 116 Hillier T A, Fagot-Campagna A, Eschwège E et al. Weight change and changes in the metabolic syndrome as the French population moves towards overweight: the D.E S.I.R. cohort.  Int J Epidemiol. 2006;  35 190-196
    Google Scholar
  • 117 Mooradian A D, Haas M J, Wehmeier K R et al. Obesity-related changes in high-density lipoprotein metabolism.  Obesity. 2008;  16 1152-1160
    Google Scholar
  • 118 Sirpal S. Myeloperoxidase-mediated lipoprotein carbamylation as a mechanistic pathway for atherosclerotic vascular disease.  Clin Sci. 2009;  116 681-695
    Google Scholar
  • 119 Shao B, Oda M N, Oram J F et al. Myeloperoxidase: an oxidative pathway for generating dysfunctional high-density lipoprotein.  Chem Res Toxicol. 2010;  23 447-454
    Google Scholar
  • 120 Williams P T, Blanche P J, Krauss R M. Behavioral versus genetic correlates of lipoproteins and adiposity in identical twins discordant for exercise.  Circulation. 2005;  112 350-356
    Google Scholar
  • 121 Ahmad T, Chasman D I, Buring J E et al. Physical activity modifies the effect of LPL, LIPC, and CETP polymorphisms on HDL-C levels and the risk of myocardial infarction in women of European ancestry.  Circ Cardiovasc Genet. 2011;  4 74-80
    Google Scholar
  • 122 Mozaffarian D, Aro A, Willet W C. Health effects of trans-fatty acids: experimental and observational evidence.  Eur J Clin Nutr. 2009;  63(2) S5-S21
    Google Scholar
  • 123 Rapp R J. Hypertriglyceridemia: a review beyond low-density lepoprotein.  Cardiol Rev. 2002;  10 163-172
    Google Scholar
  • 124 Oram J F, Heinecke J W. ATP-binding cassette transporter A1: a ceII cholesterol exporter that protects against cardiovascular disease.  Physiol Rev. 2005;  85 1343-1372
    Google Scholar
  • 125 Schaefer E J, Santos R D, Asztalos B F. Marked HDL deficiency and premature coronary heart disease.  Curr Opin Lipidol. 2010;  21 289-297
    Google Scholar
  • 126 Hovingh G K, Brownlie A, Bisoendial R J et al. A novel apoA-I mutation (L178P) leads to endothelial dysfunction, increased arterial wall thickness, and primature coronary artery disease.  J AM Coll Cardiol. 2004;  44 1429-1435
    Google Scholar
  • 127 Miller M, Zhan M. Genetic determinants of low high-density lipoprotein cholesterol.  Curr Opin Cardiol. 2004;  19 380-384
    Google Scholar
  • 128 Pocovi M, Cenarro A, Civeira F et al. Beta-glucocerebrosidase gene locus as a link for Gaucher’s disease and familial hypo-alpha-lipoproteinaemia.  Lancet. 1998;  351 1919-1923
    Google Scholar

Univ.-Prof. Dr. med. Bodo Levkau

Institut für Pathophysiologie
Zentrum für Innere Medizin
Universitätsklinikum Essen

Hufelandstraße 55
45122 Essen

Phone: 0201/723–4414

Email: levkau@uni-essen.de