Oficiálny časopis Slovenskej kardiologickej spoločnosti,
Slovenskej hypertenziologickej spoločnosti a Slovenskej asociácie srdcových arytmií

Cardiology Letters 2014, 23(3):197-206

Nové liečebné prístupy k dyslipidémii

Murín J, Pernický M, Kiňová S
I. interná klinika LFUK a UNB Staré mesto v Bratislave, Slovenská republika

Kardiovaskulárne ochorenia sú hlavnou príčinou mortality a morbidity vo svete i u nás. Významným rizikovým faktorom vzniku týchto ochorení je dyslipidémia, najmä hypercholesterolémia. Zníženie sérovej hladiny LDL cholesterolu (diétou, ale predovšetkým farmakologickou liečbou) významne redukuje kardiovaskulárne riziko pacientov. V oblasti zníženia sérovej LDL cholesterolémie máme k dispozícii statíny (najmä silné a užívané vo vysokých dávkach), ezetimib a ich vzájomnú kombinačnú liečbu. Avšak prichádzajú aj nové lieky. Sú to inhibítory produkcie apolipoproteínu B (mipomersen), inhibítory aktivity mikrozomálneho transfer-proteínu triacylglycerolov (lomitapib), látky podporujúce lipoproteínový katabolizmus (najmä inhibítory PCSK9, od ktorých dnes veľa očakávame) a ešte sem zaraďujeme ďalšie látky, kde spomenieme ETC-1002. Iným prístupom je zvyšovanie sérovej hladiny HDL cholesterolu a čakáme na výsledky klinických štúdií s anacetrapibom a evacetrapibom. A je i záujem priaznivo ovplyvniť lipoproteín Lp(a), hoci veľa liečebných možnosti tu nemáme. O tom je článok, teda o tom, kde sa dnes nachádzame v oblasti hypolipidemickej liečby.

Kľúčové slová: kardiovaskulárne ochorenia; hypercholesterolémia; LDL cholesterol; statíny; ezetimib; nové hypolipidemiká

Uverejnené: March 1, 2014  Zobraziť citáciu

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Murín J, Pernický M, Kiňová S. Nové liečebné prístupy k dyslipidémii. Cardiology Letters. 2014;23(3):197-206.
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    Referencie

    1. Nichols M, Townsend N, Luengo-Fernandez R, et al. European Cardiovascular Disease Statistics 2012. European Heart Network, Brussels, European Society of Cardiology, Sophia Antipolis.
    2. Wild S, Roglic G, Green A, et al. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047-1053. Prejsť k pôvodnému zdroju...
    3. Perk J, De Backer G, Gohlke H, et al. 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). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACRP). Eur Heart J 2012;33:1635-1701.
    4. Baigent C, Keech A, Kearney PM, et al. Cholesterol Treatment Trialists' (CTT) Collaborators: Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005;366:1267-1278. Prejsť k pôvodnému zdroju...
    5. Cholesterol Treatment Trialists' (CTT) Collaborators, Kearney PM, Blackwell L, Collins R et al. Efficacy of cholesterol-lowering therapy in 18.686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008;371:117-125. Prejsť k pôvodnému zdroju...
    6. Grundy SM, Cleeman JI, Merz CN, et al. National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227-239. Prejsť k pôvodnému zdroju...
    7. Fourth Joint Task Force of the European Society of Cardiology and other Societies on Cardiovascular disease Prevention in Clinical practice: European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Eur Heart J 2007;28:2375-2414.
    8. Shah PK, Kaul S, Nilsson J, et al. Exploiting the vascular protect­ ive effects of high density lipoprotein and its apolipoproteins: an idea whose time for testing is coming. Part I. Circulation 2001;104:2376-2383. Prejsť k pôvodnému zdroju...
    9. Gotto AM Jr. High-density lipoprotein cholesterol and triglycer­ ides as therapeutic targets for preventing and treating coronary artery disease. Am Heart J 2002;144(Suppl 6):S33-S42. Prejsť k pôvodnému zdroju...
    10. Barter PJ, Puranik R, Rye KA. New insights into the role of HDL as an anti-inflammatory agent in the prevention of cardiovascular disease. Curr Cardiol Rep 2007;9:493-449. Prejsť k pôvodnému zdroju...
    11. McBride P. Triglycerides and risk for coronary artery disease. Curr Atheroscler Rep 2008;10:386-390. Prejsť k pôvodnému zdroju...
    12. Kotseva K, Wood D, De Backer G, et al. EUROASPIRE Study Group: Cardiovascular prevention guidelines in daily practice: a comparison of EUROASPIRE I, II, and III surveys in eight European countries, Lancet 2009;373:929-940. Prejsť k pôvodnému zdroju...
    13. Van Ganse E, Laforest L, Bure T et al. Mixed dyslipidemia among patients using lipid-lowering therapy in French general practice: an observational study. Clin Ther 2007;29:1671-1681. Prejsť k pôvodnému zdroju...
    14. HPS2-THRIVE Collaborative Group. HPS2-THRIVE random­ ized 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. European Heart Journal 2013; 34:1279-1291. Prejsť k pôvodnému zdroju...
    15. Preiss D, Tikkanen MJ, Welsh P, et al. Lipid-Modifying Therapies and Risk of Pancreatitis. A Meta-analysis. JAMA 2012;308:804811. Prejsť k pôvodnému zdroju...
    16. Phatak H, Wentworth C, Sazonov V, et al. Prevalence and predictors of lipid abnormalities in patients treated with statins in the UK general practice. Atherosclerosis 2009;202:225-233. Prejsť k pôvodnému zdroju...
    17. Garcia-Calvo M, Lisnock J, Bull HG, et al. The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A 2005;102:8132-8137. Prejsť k pôvodnému zdroju...
    18. Sudhop T, Lütjohann D, Kodal A, et al. Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation 2002;106:1943-1948. Prejsť k pôvodnému zdroju...
    19. Bays HE, Neff D, Tomassini JE, et al. Ezetimib: cholesterol lowering and beyond. Expert Rev Cardiovas Ther 2008;6:447-470. Prejsť k pôvodnému zdroju...
    20. Firas J, Al Badarin MD, Iftikhar J, et al. Impact of ezetimibe on atherosclerosis: Is the jury still out ? Mayo Clin Proc 2009;84:353-361. Prejsť k pôvodnému zdroju...
    21. Bays HE, Moore PB, Drehobl MA, et al. Ezetimibe Study Group. Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies Clin Ther 2001;23:1209-1230. Prejsť k pôvodnému zdroju...
    22. Knopp RH, Dujovne CA, Le Beaut A and Ezetimibe Study Group. Evaluation of the efficacy, safety, and tolerability of ezetimibe in primary hypercholesterolaemia: a pooled analysis from two controlled phase III clinical studies. Int J Clin Pract 2003;57:363368. Prejsť k pôvodnému zdroju...
    23. Kalogirou M, Tsimihodimos V, Gazi I, et al. Effect of ezetimibe monotherapy on the concentration of lipoprotein subfractions in patients with primary dyslipidaemia. Curr Med Res Opin 2007;23:1169-1176. Prejsť k pôvodnému zdroju...
    24. Lally SE, Owens D, Tomkin GH. Sitosterol and cholesterol in chylomicrons of type 2 diabetic and non-diabetic subjects: the relationship with ATP binding cassette proteins G5 and G8 and Niemann-PickC1-like 1 mRNA. Diabetologia 2007;50:217219. Prejsť k pôvodnému zdroju...
    25. Sandoval JC. Molecular Mechanism of Ezetimibe-induced Atten­ uation of postprandial Hypertriglyceridemia. J Atheroscler Thromb 2010;17:914-924. Prejsť k pôvodnému zdroju...
    26. Bajaj M, Suraamornkul S, Kashyap S, et al. Sustained reduction in plasma free fatty acid concentration improves insulin action without altering plasma adipocytokine levels in subjects with strong family history of type 2 diabetes. J Clin Endocrinol Metab 2004;89:4649-4655. Prejsť k pôvodnému zdroju...
    27. Ferrieres J, Amber V, Crisan O, et al. Total Lipid Management and Cardiovascular Disease in the Dyslipidemia International Study. Cardiology 2013;125:154-163. Prejsť k pôvodnému zdroju...
    28. Leiter LA, XZ, AB, et al. Lipid-altering efficacy and safety profile of combination therapy with eyetimibe/statin vs statin mono­ therapy in patients with and without diabetes: an analysis of pooled data from 27 clinical trials. Diabetes, Obesity and Metabolism 2011;13:615-628. Prejsť k pôvodnému zdroju...
    29. Cannon ChP, et al. Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): Comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am Heart J 2008;156:826-832. Prejsť k pôvodnému zdroju...
    30. Fleg JL, Mete M, Howard BV, et al. Effect of statins alone versus statins plus ezetimibe on carotid atherosclerosis in type 2 dia­ betes: the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial. J Am Coll Cardiol 2008;52:2198-2205. Prejsť k pôvodnému zdroju...
    31. Meaney A, Ceballos G, Asbun J, et al. The Vytorin on Carotid Intima-Media Thickness and Overall Arterial Rigidity (VYCTOR) Study. J Clin Pharmacol 2009;49:838-847. Prejsť k pôvodnému zdroju...
    32. Kashani A, Sallam T, Bheemreddy S, et al. Review of side-effect profile of combination ezetimibe and statin therapy in random­ ized clinical trials. Am J Cardiol 2008;101:1606-1613. Prejsť k pôvodnému zdroju...
    33. Baigent C, Landray MJ, Reith C, et al. for the SHARP Investigators. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomized trial. Lancet 2011;377:2181-2192. Prejsť k pôvodnému zdroju...
    34. Nordestgaard BG, Chapman MJ, Humphries S, et al. Familiar hypercholesterolemia is underdiagnosed and undertreated in the general population. Consensus statement of the Eur Atheroscl Society. Eur Heart J 2013;34:3478-3490. Prejsť k pôvodnému zdroju...
    35. 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 random­ ization analysis. J Am Coll Cardiol 2012;60:2631-2639. Prejsť k pôvodnému zdroju...
    36. Berry JD, Dyer A, Cai X, et al. Lifetime risks of cardiovascular disease. N Engl J Med 2012;366:321-329. Prejsť k pôvodnému zdroju...
    37. Visser ME, Witztum JL, Stroes ES, Kastelein JJ. Antisense oligonucleotides for the treatment of dyslipidemia. Eur Heart J 2012; 33:1451-1458. Prejsť k pôvodnému zdroju...
    38. Calandra S, Tarugi P, Speedy HE, et al. Mechanisms and genetic determinents regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and diasease risk. J Lipid Res 2011;52:1885-1926. Prejsť k pôvodnému zdroju...
    39. Samaha FF, McKenney J, Bloedon LT, et al. Inhibition of microsomal triglyceride transfer protein alone or with ezetimibe in patients with moderate hypercholesterolemia. Nat Clin Pract Cardiovasc Med 2008;5:497 -505. Prejsť k pôvodnému zdroju...
    40. Lambert G, Sjouke B, Choque B, et al. The PCSK9 decade. J Lipid Research 2012;53:2515-2524. Prejsť k pôvodnému zdroju...
    41. Cohen J, Pertsemlidis A, Kotowski IK, et al. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet 2005;37:161-165. Prejsť k pôvodnému zdroju...
    42. 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;354:1264-1272. Prejsť k pôvodnému zdroju...
    43. Park SW, Moon YA, and Horton JD. Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9 in a mouse liver. J Biol Chem 2004;279:50630-50638. Prejsť k pôvodnému zdroju...
    44. Lalanne F, Lamert G, Amar MJ, et al. Wild-type PCSK9 inhibits LDL cleareance but does not affect apoB-containing lipoprotein production in mouse and cultured cells. J Lipid Res 2005;46:1312-1319. Prejsť k pôvodnému zdroju...
    45. Zaid A, Roubisova A, Essalmani R, et al. Proprotein convertase subtilisin/kexin type 9 (PCSK9): hepatocyte-specific lowdensity lipoprotein receptor degradation and critical role in mouse liver regereration. Hepatology 2008;48:646-654. Prejsť k pôvodnému zdroju...
    46. Lagace TA, Curtis DE, Garuti R, et al. Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice. J Clin Invest 2006;116:2995-3005. Prejsť k pôvodnému zdroju...
    47. Li J, Tumanut C, Gavigan JA, et al. Secreted PCSK9 promotes LDL receptor degradation independently of proteolytic activity. Biochem J 2007;406:203-207. Prejsť k pôvodnému zdroju...
    48. Huijgen R, Boekholdt SM, Arsenault BJ, et al. Plasma PCSK9 levels and clinical outcomes in the treating to new targets trial: a nested case-control study. J Am Coll Cardiol 2012;59:17781784. Prejsť k pôvodnému zdroju...
    49. Lambert G, Jarnoux AL, Pineau T, et al. Fasting induces hyperlipidemia in mice overexpressing proprotein convertase subtilisin kexin type 9: lack of modulation of very-low-density-lipoprotein hepatic output by the low-density lipoprotein receptor. Endocrinology 2006;147:4985-4995. Prejsť k pôvodnému zdroju...
    50. Jeong HJ, Lee HS, Kim KS, et al. Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2. J Lipid Res 2008;49:399-409. Prejsť k pôvodnému zdroju...
    51. Careskey HE, Davis RA, Alborn WE, et al. Atorvastatin increases human serum levels of proprotein convertase subtilisin/kexin type 9. J Lipid Res 2008;49:394-398. Prejsť k pôvodnému zdroju...
    52. 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;79:514-523. Prejsť k pôvodnému zdroju...
    53. Hooper AJ, Marais AD, Tanyanyiwa DM, et al. The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population. Atherosclerosis 2007;193:445-448. Prejsť k pôvodnému zdroju...
    54. Graham MJ, Lemonidis KM, Whipple CP, et al. Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice. J Lipid Res 2007;48:763-767. Prejsť k pôvodnému zdroju...
    55. Shan L, Pang L, Zhang R, et al. PCSK9 binds to multiple receptors and can be functionally inhibited by an EGF-A peptide. Biochem Biophys Res Commun 2008;375:69-73. Prejsť k pôvodnému zdroju...
    56. Duff CJ, Scott MJ, Kirby IT, et al. Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J 2009;419:577-584. Prejsť k pôvodnému zdroju...
    57. Bergeron R, Ren JM, Cadman KS, et al. Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis. Am J Physiol Endocrinol Metab 2001;281:E1340-E1346. Prejsť k pôvodnému zdroju...
    58. Holmes BF, Kurth/Kraczek EJ, Winder WW. Chronic activation of 5´-AMP-activated protein kinase increases Glut-4, hexokinase and glycogen in muscle. J Appl Physiol 1999;87:1990-1995. Prejsť k pôvodnému zdroju...
    59. Ojuka EO, Jones TE, Nolte LA, et al. Regulation of Glut-4 biogenesis in muscle: evidence for involvement of AMPK and calcium(2+). Am J Physiol Endocrinol Metab 2002;282:E1008-E1013. Prejsť k pôvodnému zdroju...
    60. Pinkosky SL, Filippov S, Srivastava RA. et al. AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism. J Lipid Res 2013;54:134-151. Prejsť k pôvodnému zdroju...
    61. Srivastava RA, Hurley TR, Brant AF. et al. A novel small molecule ETC-1002, lowers proatherogenic lipoproteins, reduces adiposity, and improves hepatic steatosis in a hyperlipidemic hamster model (abstr 25085). Presented at: American Heart Association Scientific Sessions 2011;November 12-16, 2011;Orlando, FL.
    62. Cramer CT, Goetz B, Hopson KL, et al. Effects of a novel dual lipid synthesis inhibitor and its potential utility in treat­ ing dyslipidemia and metabolic syndrome. J Lipid Res 2004;45:1289-1301. Prejsť k pôvodnému zdroju...
    63. Ballantyne ChM, Davidson MH, MacDougal DE, et al. Efficacy and safety of a Novel Dual Modulator of Adenosine Triphosphate - Citrate Lyase and Adenosine Monophosphate - Activated Protein Kinase in Patients with Hypercholesterolemia. J Am Coll Cardiol 2013;62:1154-1162. Prejsť k pôvodnému zdroju...
    64. Degoma EM, Rader DJ. Novel HDL-directed pharmacotherapeutic strategies. Nat Rev Cardiol 2011;8:266-277. Prejsť k pôvodnému zdroju...
    65. Khera AV, Rader DJ. Future therapeutic directions in reverse cholesterol transport. Curr Atheroscler Rep 2010;12:73-81. Prejsť k pôvodnému zdroju...
    66. Rye KA, Bursil CA, Lambert G, et al. The metabolism and antiatherogenic properties of HDL. J Lipid Res 2009;50(Suppl):S195-S200. Prejsť k pôvodnému zdroju...
    67. Rayner KJ, Esau CC, Hussain FN, et al. Inhibition of miR-33a/b in nonhuman primates raises plasma HDL and lowers VlDL triglycerides. Nature 2011;478:404-407. Prejsť k pôvodnému zdroju...
    68. Klerkx AH, EI Harchaoui K, van der Steeg WA, et al. Cholesteryl ester transfer protein (CETP) inhibition beyond raising high-density lipoprotein cholesterol levels: pathways by which modulation of CETP acitivity may alter atherogenesis. Arterio­ scler Thromb Vasc Biol 2006;26:706-715. Prejsť k pôvodnému zdroju...
    69. Niesor EJ, Magg C, Ogawa N, et al. Modulating cholesteryl ester transfer protein activity maintains efficient prebeta-HDL formation and increases reverse cholesterol transport. J Lipid Res2010;51:3443-3454. Prejsť k pôvodnému zdroju...
    70. Von Eckardstein A. Mulling over the odds of CETP inhibition. Eur Heart J 2010;31:390-393. Prejsť k pôvodnému zdroju...
    71. Weissglas-Volkov D, Pajukanta P. Genetic causes of high and low serum HDL-cholesterol. J Lipid Res 2010;51:2032-2057. Prejsť k pôvodnému zdroju...
    72. Gotto AM, Jennifer E, Moon A. Safety of inhibition of cholesteryl ester transfer protein with anacetrapib: the DEFINE study. Expert Rev Cardiovasc Ther 2012;10:955-963. Prejsť k pôvodnému zdroju...
    73. Gutstein DE, R Krishna L, Johns D, et al. Anacetrapib, a Novel CETP Inhibitor: Pursuing a New Approach to Cardiovascular Risk Reduction. Clin pharmacol and therapeutics 2012;91:109-122. Prejsť k pôvodnému zdroju...
    74. Protocol I1V-MC-EIAN Assessment of Clinical Effects of Chol­ esteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at High/Risk for vascular Outcomes - the ACCELERATE Study.
    75. 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. Prejsť k pôvodnému zdroju...
    76. Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein (a) as a cardiovascular risk factor: current status. Eur Heart J 2010;31:2844-2853. Prejsť k pôvodnému zdroju...
    77. Kolski B, Tsimikas S. Emerging therapeutic agents to lower lipoprotein (a) levels. Curr Opin Lipidol 2012;23:560-568. Prejsť k pôvodnému zdroju...
    78. Stein EA, Mellis S, Yancopoulos GD, et al. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med 2012;366:1108-1118. Prejsť k pôvodnému zdroju...

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