nach oben

Current Cardiology Reports

Erschienen in:

01.08.2019 | Lipid Abnormalities and Cardiovascular Prevention (G De Backer, Section Editor)

Genetics, Dyslipidemia, and Cardiovascular Disease: New Insights

verfasst von: Ricardo Stein, Filipe Ferrari, Fernando Scolari

Erschienen in: Current Cardiology Reports | Ausgabe 8/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

The cardiovascular (CV) risk related to lipid disorders is well established and is based on a robust body of evidence from well-designed randomized clinical trials, as well as prospective observational studies. In the last two decades, significant advances have been made in understanding the genetic basis of dyslipidemias. The present review is intended as a comprehensive discussion of current knowledge about the genetics and pathophysiology of disorders that predispose to dyslipidemia. We also focus on issues related to statins and the proprotein convertase subtilisin/kexin type 9 (PCSK9) and some of its polymorphisms, as well as new cholesterol-lowering medications, including PCSK9 inhibitors.

Recent Finding

Cholesterol is essential for the proper functioning of several body systems. However, dyslipidemia—especially elevated low-density lipoprotein (LDL-c) and triglyceride levels, as well as reduced lipoprotein lipase activity—is associated with an increased risk of coronary artery disease (CAD). High-density lipoprotein (HDL-c), however, seems to play a role as a risk marker rather than as a causal factor of the disease, as suggested by Mendelian randomization studies. Several polymorphisms in the lipoprotein lipase locus have been described and are associated with variations in the activity of this enzyme, producing high concentrations of triglycerides and increased risk of CAD.

Summary

Dyslipidemia, especially increased LDL-c and triglyceride levels, continues to play a significant role in CV risk. The combination of genetic testing and counseling is important in the management of patients with dyslipidemia of genetic etiology. Strategies focused on primary prevention can offer an opportunity to reduce CV events.

Pol T, Held C, Westerbergh J, Lindbäck J, Alexander JH, Alings M, et al. Dyslipidemia and risk of cardiovascular events in patients with atrial fibrillation treated with oral anticoagulation therapy: insights from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) Trial. J Am Heart Assoc. 2018;7(3):e007444. https://doi.org/10.1161/JAHA.117.007444.CrossRefPubMedPubMedCentral

Carroll MD, Fryar CD, Nguyen DT. Total and high-density lipoprotein cholesterol in adults: United States, 2015-2016. NCHS Data Brief. 2017;290:1–8 Available from https://www.cdc.gov.

Faggiano P, Pirillo A, Griffo R, Ambrosetti M, Pedretti R, Scorcu G, et al. Prevalence and management of familial hypercholesterolemia in patients with coronary artery disease: the heredity survey. Int J Cardiol. 2018;252:193–8. https://doi.org/10.1016/j.ijcard.2017.10.105.CrossRefPubMed

Tietjen I, Hovingh GK, Singaraja R, Radomski C, McEwen J, Chan E, et al. Increased risk of coronary artery disease in Caucasians with extremely low HDL cholesterol due to mutations in ABCA1, APOA1, and LCAT. Biochim Biophys Acta. 2012;1821:416–24. https://doi.org/10.1016/j.bbalip.2011.08.006.CrossRefPubMed

Sadananda SN, Foo JN, Toh MT, Cermakova L, Trigueros-Motos L, Chan T, et al. Targeted next-generation sequencing to diagnose disorders of HDL cholesterol. J Lipid Res. 2015;56:1993–2001. https://doi.org/10.1194/jlr.P058891.CrossRefPubMedPubMedCentral

Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357(21):2109–22. https://doi.org/10.1056/NEJMoa0706628.CrossRefPubMed

Tall AR, Yvan-Charvet L, Wang N. The failure of torcetrapib: was it the molecule or the mechanism? Arterioscler Thromb Vasc Biol. 2007;27(2):257–60. https://doi.org/10.1161/01.ATV.0000256728.60226.77.CrossRefPubMed

Mattu RK, Needham EW, Morgan R, Rees A, Hackshaw AK, Stocks J, et al. DNA variants at the LPL gene locus associate with angiographically defined severity of atherosclerosis and serum lipoprotein levels in a Welsh population. Arterioscler Thromb. 1994;14(7):1090–7. https://doi.org/10.1161/01.ATV.14.7.1090.CrossRefPubMed

Xie L, Li YM. Lipoprotein lipase (LPL) polymorphism and the risk of coronary artery disease: a meta-analysis. Int J Environ Res Public Health. 2017;14(1). https://doi.org/10.3390/ijerph14010084.CrossRefPubMedCentral

10.

Kohan AB. Apolipoprotein C-III: a potent modulator of hypertriglyceridemia and cardiovascular disease. Curr Opin Endocrinol Diabetes Obes. 2015;22(2):119–25. https://doi.org/10.1097/MED.0000000000000136.CrossRefPubMedPubMedCentral

11.

TG and HDL Working Group of the Exome Sequencing Project, National Heart, Lung, and Blood Institute Crosby J Peloso G Auer P Crosslin D, et al. Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N Engl J Med. 2014;371(1):22–31. https://doi.org/10.1056/NEJMoa1307095. CrossRef

12.

Zhang JZ, Xie X, Ma YT, Zheng YY, Yang YN, Li XM, et al. Association between apolipoprotein C-III gene polymorphisms and coronary heart disease: a meta-analysis. Aging Dis. 2016;7(1):36–44. https://doi.org/10.14336/AD.2015.0709.CrossRefPubMedPubMedCentral

13.

Rasmussen JN, Chong A, Alter DA. Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA. 2007;297:177–86. https://doi.org/10.1001/jama.297.2.177.CrossRefPubMed

14.

Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA. Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmacogenomics Pers Med. 2016;9:97–106. https://doi.org/10.2147/PGPM.S86013.CrossRef

15.

Ramsey LB, Johnson SG, Caudle KE, Haidar CE, Voora D, Wilke RA, et al. The Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clin Pharmacol Ther. 2014;96(4):423–8. https://doi.org/10.1038/clpt.2014.125.CrossRefPubMedPubMedCentral

16.

Armitage J, Holmes MV, Preiss D. Cholesteryl ester transfer protein inhibition for preventing cardiovascular events: JACC Review Topic of the Week. J Am Coll Cardiol. 2019;73(4):477–48. https://doi.org/10.1016/j.jacc.2018.10.072.CrossRefPubMedPubMedCentral

17.

Webb TR, Erdmann J, Stirrups KE, Stitziel NO, Masca N1, Jansen H, et al. Systematic evaluation of pleiotropy identifies 6 further loci associated with coronary artery disease. J Am Coll Cardiol. 2017;69:823–36. https://doi.org/10.1016/j.jacc.2016.11.056.CrossRefPubMedPubMedCentral

18.

Boekholdt SM, Sacks FM, Jukema JW, Shepherd J, Freeman DJ, McMahon AD, et al. Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment: individual patient meta-analysis of 13,677 subjects. Circulation. 2005;111:278–87. https://doi.org/10.1161/01.CIR.0000153341.46271.40.CrossRefPubMed

19.

Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–22. https://doi.org/10.1056/NEJMoa1615664.CrossRefPubMed

20.

Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(22):2097–107. https://doi.org/10.1056/NEJMoa1801174.CrossRefPubMed

21.

Natarajan P, Young R, Stitziel NO, Padmanabhan S, Baber U, Mehran R, et al. Polygenic risk score identifies subgroup with higher burden of atherosclerosis and greater relative benefit from statin therapy in the primary prevention setting. Circulation. 2017;135(22):2091–101. https://doi.org/10.1161/CIRCULATIONAHA.116.024436.CrossRefPubMedPubMedCentral

22••.

Khera AV, Emdin CA, Drake I, Natarajan P, Bick AG, Cook NR, et al. Genetic risk, adherence to a healthy lifestyle, and coronary disease. N Engl J Med. 2016;375(24):2349–58. https://doi.org/10.1056/NEJMoa1605086 The results of this study showed that in individuals with high genetic risk for coronary artery disease, the adoption of healthy lifestyle habits can reduce the relative risk of coronary heart disease by 50%, when compared with those individuals with unhealthy lifestyle. CrossRefPubMedPubMedCentral

23.

Sjouke B, Kusters DM, Kindt I, Besseling J, Defesche JC, Sijbrands EJ, et al. Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: prevalence, genotype-phenotype relationship, and clinical outcome. Eur Heart J. 2015;36(9):560–5. https://doi.org/10.1093/eurheartj/ehu058.CrossRefPubMed

24.

Turgeon RD, Barry AR, Pearson GJ. Familial hypercholesterolemia: review of diagnosis, screening, and treatment. Can Fam Physician. 2016;62(1):32–7 Availabe at http://www.cfp.ca.PubMedPubMedCentral

25.

Migliara G, Baccolini V, Rosso A, D'Andrea E, Massimi A, Villari P, et al. Familial hypercholesterolemia: a systematic review of guidelines on genetic testing and patient management. Front Public Health. 2017;5:252. https://doi.org/10.3389/fpubh.2017.00252.CrossRefPubMedPubMedCentral

26.

Onorato A, Sturm AC. Heterozygous familial hypercholesterolemia. Circulation. 2016;133(14):e587–9. https://doi.org/10.1161/CIRCULATIONAHA.115.020701.CrossRefPubMed

27.

Poonia A, Giridhara P. Xanthomas in familial hypercholesterolemia. N Engl J Med. 2017;377(5):e7. https://doi.org/10.1056/NEJMicm161614.CrossRefPubMed

28.

Wang X, Jiang L, Sun LY, Wu Y, Wen WH, Wang XF, et al. Genetically confirmed familial hypercholesterolemia in outpatients with hypercholesterolemia. J Geriatr Cardiol. 2018;15(6):434–40. https://doi.org/10.11909/j.issn.1671-5411.2018.06.006.CrossRefPubMedPubMedCentral

29.

Bouhairie EV, Goldberg AC. Familial hypercholesterolemia. Cardiol Clin. 2015;33(2):169–79. https://doi.org/10.1016/j.ccl.2015.01.001.CrossRefPubMedPubMedCentral

30.

Kataoka Y, Harada-Shiba M, Nakao K, Nakashima T, Kawakami S, Fujino M, et al. Mature proprotein convertase subtilisin/kexin type 9, coronary atheroma burden, and vessel remodeling in heterozygous familial hypercholesterolemia. J Clin Lipidol. 2017;11(2):413–421.e3. https://doi.org/10.1016/j.jacl.2017.01.005.CrossRefPubMed

31.

Thompson GR, Blom DJ, Marais AD, Seed M, Pilcher GJ, Raal FJ. Survival in homozygous familial hypercholesterolaemia is determined by the on-treatment level of serum cholesterol. Eur Heart J. 2018;39(14):1162–8. https://doi.org/10.1093/eurheartj/ehx317.CrossRefPubMed

32.

Aljenedil S, Ruel I, Watters K, Genest J. Severe xanthomatosis in heterozygous familial hypercholesterolemia. J Clin Lipidol. 2018;12(4):872–7. https://doi.org/10.1016/j.jacl.2018.03.087.CrossRefPubMed

33.

Li JJ, Li S, Zhu CG, Wu NQ, Zhang Y, Guo YL, et al. Familial hypercholesterolemia phenotype in Chinese patients undergoing coronary angiography. Arterioscler Thromb Vasc Biol. 2017;37(3):570–9. https://doi.org/10.1161/ATVBAHA.116.308456.CrossRefPubMed

34.

Sturm AC, Knowles JW, Gidding SS, Ahmad ZS, Ahmed CD, Ballantyne CM, et al. Clinical genetic testing for familial hypercholesterolemia: JACC Scientific Expert Panel. J Am Coll Cardiol. 2018;72(6):662–80. https://doi.org/10.1016/j.jacc.2018.05.044.CrossRefPubMed

35.

Khera AV, Won HH, Peloso GM, Lawson KS, Bartz TM, Deng X, et al. Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol. 2016;67(22):2578–89. https://doi.org/10.1016/j.jacc.2016.03.520.CrossRefPubMedPubMedCentral

36.

Henderson R, O'Kane M, McGilligan V, Watterson S. The genetics and screening of familial hypercholesterolaemia. J Biomed Sci. 2016;23:39. https://doi.org/10.1186/s12929-016-0256-1.CrossRefPubMedPubMedCentral

37.

Iacocca MA, Hegele RA. Recent advances in genetic testing for familial hypercholesterolemia. Expert Rev Mol Diagn. 2017;17(7):641–51. https://doi.org/10.1080/14737159.2017.1332997.CrossRefPubMed

38.

WHO Human Genetics Programme. Familial hypercholesterolaemia (FH): report of a second WHO consultation [online]. http://apps.who.int/iris/handle/10665/66346 (1998).

39.

Defesche JC, Lansberg PJ, Umans-Eckenhausen MA, Kastelein JJ. Advanced method for the identification of patients with inherited hypercholesterolemia. Semin Vasc Med. 2004;49(1):59–65.CrossRef

40.

Besser J, Carleton HA, Gerner-Smidt P, Lindsey RL, Trees E. Next-generation sequencing technologies and their application to the study and control of bacterial infections. Clin Microbiol Infect. 2018;24(4):335–41. https://doi.org/10.1016/j.cmi.2017.10.013.CrossRefPubMed

41.

Prospective Studies Collaboration, Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet. 2007;370(9602):1829–39. https://doi.org/10.1016/S0140-6736(07)61778-4.CrossRef

42.

Catapano AL, Pirillo A, Norata GD. Vascular inflammation and low-density lipoproteins: is cholesterol the link? A lesson from the clinical trials. Br J Pharmacol. 2017;174(22):3973–85. https://doi.org/10.1111/bph.CrossRefPubMedPubMedCentral

43.

Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459–72. https://doi.org/10.1093/eurheartj/ehx144.CrossRefPubMedPubMedCentral

44•.

Silverman MG, Ference BA, Im K, Wiviott SD, Giugliano RP, Grundy SM, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA. 2016;316(12):1289–97. https://doi.org/10.1001/jama.2016.13985 In this analysis, with more than 300,000 individuals included, it confirms that achieving lower levels of LDL is associated with lower rates of major coronary events. A reduction of 1.5% and 4.6% in the rate of major cardiovascular events (cardiovascular death and acute myocardial infarction) was observed for each reduction of 1 mmol/L in LDL in primary and secondary prevention studies, respectively.CrossRefPubMed

45.

Navarese EP, Robinson JG, Kowalewski M, Kolodziejczak M, Andreotti F, Bliden K, et al. Association between baseline LDL-C level and total and cardiovascular mortality after LDL-C lowering: a systematic review and meta-analysis. JAMA. 2018;319(15):1566–79. https://doi.org/10.1001/jama.2018.2525.CrossRefPubMedPubMedCentral

46.

Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010;466(7307):707–13. https://doi.org/10.1038/nature09270.CrossRefPubMedPubMedCentral

47.

Talmud PJ, Shah S, Whittall R, Futema M, Howard P, Cooper JA, et al. Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-control study. Lancet. 2013;381:1293–301. https://doi.org/10.1016/S0140-6736(12)62127-8.CrossRefPubMed

48.

Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302:1993–2000. https://doi.org/10.1001/jama.2009.1619.CrossRefPubMed

49.

Rosenson RS. The high-density lipoprotein puzzle: why classic epidemiology, genetic epidemiology, and clinical trials conflict? Arterioscler Thromb Vasc Biol. 2016;36(5):777–82. https://doi.org/10.1161/ATVBAHA.116.307024.CrossRefPubMed

50.

Voight BF, Peloso GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen MK, et al. Plasma HDL cholesterol and risk of myocardial infarction: a Mendelian randomisation study. Lancet. 2012;380(9841):572–80. https://doi.org/10.1016/S0140-6736(12)60312-2.CrossRefPubMedPubMedCentral

51.

Kawashiri MA, Tada H, Nomura A, Yamagishi M. Mendelian randomization: its impact on cardiovascular disease. J Cardiol. 2018;72(4):307–13. https://doi.org/10.1016/j.jjcc.2018.04.007.CrossRefPubMed

52.

Haase CL, Tybjærg-Hansen A, Grande P, Frikke-Schmidt R. Genetically elevated apolipoprotein A-I, high-density lipoprotein cholesterol levels, and risk of ischemic heart disease. J Clin Endocrinol Metab. 2010;95:E500–10. https://doi.org/10.1210/jc.2010-0450.CrossRefPubMed

53.

Vergeer M, Holleboom AG, Kastelein JJ, Kuivenhoven JA. The HDL hypothesis: does high-density lipoprotein protect from atherosclerosis? J Lipid Res. 2010;51(8):2058–73. https://doi.org/10.1194/jlr.R001610.CrossRefPubMedPubMedCentral

54.

Zhong S, Sharp DS, Grove JS, Bruce C, Yano K, Curb JD, et al. Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels. J Clin Invest. 1996;97(12):2917–23. https://doi.org/10.1172/JCI118751.CrossRefPubMedPubMedCentral

55.

Cohen JC, Kiss RS, Pertsemlidis A, Marcel YL, McPherson R, Hobbs HH. Multiple rare alleles contribute to low plasma levels of HDL cholesterol. Science. 2004;305:869–72. https://doi.org/10.1126/science.1099870.CrossRefPubMed

56.

Abdel-Razek O, Sadananda SN, Li X, Cermakova L, Frohlich J, Brunham LR. Increased prevalence of clinical and subclinical atherosclerosis in patients with damaging mutations in ABCA1 or APOA1. J Clin Lipidol. 2018;12(1):116–21. https://doi.org/10.1016/j.jacl.2017.10.010.CrossRefPubMed

57.

Hassan M, Philip P. CANHEART: is HDL cholesterol a cardiovascular specific risk factor? Glob Cardiol Sci Pract. 2016;2016(4):e201634. https://doi.org/10.21542/gcsp.2016.34.CrossRefPubMedPubMedCentral

58.

Hooper AJ, Crawford GM, Brisbane JM, Robertson K, Watts GF, van Bockxmeer FM, et al. Familial lipoprotein lipase deficiency caused by known (G188E) and novel (W394X) LPL gene mutations. Ann Clin Biochem. 2008;45(Pt 1):102–5. https://doi.org/10.1258/acb.2007.007080.CrossRefPubMed

59.

Ashraf AP, Beukelman T, Pruneta-Deloche V, Kelly DR, Garg A. Type 1 hyperlipoproteinemia and recurrent acute pancreatitis due to lipoprotein lipase antibody in a young girl with Sjogren’s syndrome. J Clin Endocrinol Metab. 2011;96(11):3302–7. https://doi.org/10.1210/jc.2011-1113.CrossRefPubMedPubMedCentral

60.

Zhang WS, Zhang WH, Liu QJ. Lipoprotein lipase gene Hind III polymorphism was associated with hemorrhagic stroke. Int J Clin Exp Med. 2015;8(6):9575–9 Available at http://www.ijcem.com/.PubMedPubMedCentral

61.

Benlian P, Foubert L, Gagné E, Bernard L, De Gennes JL, Langlois S, et al. Complete paternal isodisomy for chromosome 8 unmasked by lipoprotein lipase deficiency. Am J Hum Genet. 1996;59(2):431–6 Available at www.cell.com.PubMedPubMedCentral

62.

Ahmadi Z, Senemar S, Toosi S, Radmanesh S. The association of lipoprotein lipase genes, HindIII and S447X polymorphisms with coronary artery disease in Shiraz City. J Cardiovasc Thorac Res. 2015;7(2):63–7. https://doi.org/10.15171/jcvtr.2015.14.CrossRefPubMedPubMedCentral

63.

Daoud MS, Ataya FS, Fouad D, Alhazzani A, Shehata AI, Al-Jafari AA. Associations of three lipoprotein lipase gene polymorphisms, lipid profiles and coronary artery disease. Biomed Rep. 2013;1(4):573–82. https://doi.org/10.3892/br.2013.126.CrossRefPubMedPubMedCentral

64.

Heng CK, He X, Saha N, Low PS, Demirci FY, Kamboh MI. Association of three lipoprotein lipase polymorphisms with coronary artery disease in Chinese and Asian Indians. Int J Cardiol. 2010;144(1):142–3. https://doi.org/10.1016/j.ijcard.2008.12.121.CrossRefPubMed

65.

Cui F, Li K, Li Y, Zhang X, An C. Apolipoprotein C3 genetic polymorphisms are associated with lipids and coronary artery disease in a Chinese population. Lipids Health Dis. 2014;13:170. https://doi.org/10.1186/1476-511X-13-170.CrossRefPubMedPubMedCentral

66.

Wang Y, Yin X, Li L, Deng S, He Z. Association of apolipoprotein C3 genetic polymorphisms with the risk of ischemic stroke in the northern Chinese Han population. PLoS One. 2016;11(9):e0163910. https://doi.org/10.1371/journal.pone.0163910.CrossRefPubMedPubMedCentral

67.

Fitzgerald K, White S, Borodovsky A, Bettencourt BR, Strahs A, Clausen V, et al. A highly durable RNAi therapeutic inhibitor of PCSK9. N Engl J Med. 2017;376(1):41–51. https://doi.org/10.1056/NEJMc1703361.CrossRefPubMed

68.

Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, Devillers M, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34:154–6. https://doi.org/10.1038/ng1161.CrossRefPubMed

69.

Qiu C, Zeng P, Li X, Zhang Z, Pan B, Peng Z, et al. What is the impact of PCSK9 rs505151 and rs11591147 polymorphisms on serum lipids level and cardiovascular risk: a meta-analysis. Lipids Health Dis. 2017;16(1):111. https://doi.org/10.1186/s12944-017-0506-6.CrossRefPubMedPubMedCentral

70.

Cai G, Zhang B, Shi G, Weng W, Ma C, Song Y. The associations between proprotein convertase subtilisin/kexin type 9 e670g polymorphism and the risk of coronary artery disease and serum lipid levels: a meta-analysis. Lipids Health Dis. 2015;14:149. https://doi.org/10.1186/s12944-015-0154-7.CrossRefPubMedPubMedCentral

71.

Adi D, Xie X, Liu F, Ma YT, Abudoukelimu M, Wu Y. Relationships between genetic polymorphisms of e670g in pcsk9 gene and coronary artery disease: a meta-analysis. Int J Clin Exp Med. 2015;8:13251–8 Available at http://www.ijcem.com/.PubMedPubMedCentral

72.

73.

Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/ PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018. https://doi.org/10.1016/j.jacc.2018.11.002.CrossRefPubMed

74.

Yebyo HG, Aschmann HE, Kaufmann K, Puhan MA. Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: a systematic review, meta-analysis and network meta-analysis of randomized trials with 94,283 participants. Am Heart J. 2019;210:18–28. https://doi.org/10.1016/j.ahj.2018.12.007.CrossRefPubMed

75.

Koskinas KC, Siontis GCM, Piccolo R, Mavridis D, Räber L, Mach F, et al. Effect of statins and non-statin LDL-lowering medications on cardiovascular outcomes in secondary prevention: a meta-analysis of randomized trials. Eur Heart J. 2018;39(14):1172–80. https://doi.org/10.1093/eurheartj/ehx566.CrossRefPubMed

76.

García-Giustiniani D, Stein R. Genetics of dyslipidemia. Arq Bras Cardiol. 2016;106(5):434–8. https://doi.org/10.5935/abc.20160074.CrossRefPubMedPubMedCentral

77.

Josephine LH, Joy SV, Haga SB, Orlando LA, Kraus WE, Ginsburg GS, et al. Genetically guided statin therapy on statin perceptions, adherence, and cholesterol lowering: a pilot implementation study in primary care patients. J Pers Med. 2014;4(2):147–62. https://doi.org/10.3390/jpm4020147.CrossRef

78.

Relling MV, Krauss RM, Roden DM, Klein TE, Fowler DM, Terada N, et al. New pharmacogenomics research network: an open community catalyzing research and translation in precision medicine. Clin Pharmacol Ther. 2017;102(6):897–902. https://doi.org/10.1002/cpt.755.CrossRefPubMed

79.

Peyser B, Perry EP, Singh K, Gill RD, Mehan MR, Haga SB, et al. Effects of delivering SLCO1B1 pharmacogenetic information in randomized trial and observational settings. Circ Genom Precis Med. 2018;11(9):e002228. https://doi.org/10.1161/CIRCGEN.118.002228.CrossRefPubMed

80.

Hoenig MR, Walker PJ, Gurnsey C, Beadle K, Johnson L. The C3435T polymorphism in ABCB1 influences atorvastatin efficacy and muscle symptoms in a high-risk vascular cohort. J Clin Lipidol. 2011;5(2):91–6. https://doi.org/10.1016/j.jacl.2011.01.001.CrossRefPubMed

81.

DeGorter MK, Tirona RG, Schwarz UI, Choi YH, Dresser GK, Suskin N, et al. Clinical and pharmacogenetic predictors of circulating atorvastatin and rosuvastatin concentrations in routine clinical care. Circ Cardiovasc Genet. 2013;6(4):400–8. https://doi.org/10.1161/CIRCGENETICS.113.000099.CrossRefPubMedPubMedCentral

82.

Wang D, Guo Y, Wrighton SA, Cooke GE, Sadee W. Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs. Pharmacogenomics J. 2011;11(4):274–86. https://doi.org/10.1038/tpj.2010.28.CrossRefPubMed

83.

Tsamandouras N, Dickinson G, Guo Y, Hall S, Rostami-Hodjegan A, Galetin A, et al. Identification of the effect of multiple polymorphisms on the pharmacokinetics of simvastatin and simvastatin acid using a population-modeling approach. Clin Pharmacol Ther. 2014;96(1):90–100. https://doi.org/10.1038/clpt.2014.55.CrossRefPubMed

84.

Thompson JF, Hyde CL, Wood LS, Paciga SA, Hinds DA, Cox DR, et al. Comprehensive whole-genome and candidate gene analysis for response to statin therapy in the Treating to New Targets (TNT) cohort. Circ Cardiovasc Genet. 2009;2:173–81. https://doi.org/10.1161/CIRCGENETICS.108.818062.CrossRefPubMed

85.

Thompson JF, Man M, Johnson KJ, Wood LS, Lira ME, Lloyd DB, et al. An association study of 43 SNPs in 16 candidate genes with atorvastatin response. Pharmacogenomics J. 2005;5:352–8. https://doi.org/10.1038/sj.tpj.6500328.CrossRefPubMed

86.

Regieli JJ, Jukema JW, Grobbee DE, Kastelein JJ, Kuivenhoven JA, Zwinderman AH, et al. CETP genotype predicts increased mortality in statin-treated men with proven cardiovascular disease: an adverse pharmacogenetic interaction. Eur Heart J. 2008;29:2792–9. https://doi.org/10.1093/eurheartj/ehn465.CrossRefPubMed

87.

Nieminen T, Kähönen M, Viiri LE, Grönroos P, Lehtimäki T. Pharmacogenetics of apolipoprotein E gene during lipid-lowering therapy: lipid levels and prevention of coronary heart disease. Pharmacogenomics. 2008;9(10):1475–86. https://doi.org/10.2217/14622416.9.10.1475.CrossRefPubMed

88.

Xiang Q, Zhang X, Ma L, Hu K, Zhang Z, Mu G, et al. The association between the SLCO1B1, apolipoprotein E, and CYP2C9 genes and lipid response to fluvastatin: a meta-analysis. Pharmacogenet Genomics. 2018;28(12):261–7. https://doi.org/10.2217/14622416.9.10.1475.CrossRefPubMed

89.

Ferrari F, Stein R, Motta MT, Moriguchi EH. PCSK9 inhibitors: clinical relevance, molecular mechanisms, and safety in clinical practice. Arq Bras Cardiol. 2019. https://doi.org/10.5935/abc.20190029.

90.

Giugliano RP, Keech A, Murphy SA, Huber K, Tokgozoglu SL, Lewis BS, et al. Clinical efficacy and safety of evolocumab in high-risk patients receiving a statin: secondary analysis of patients with low LDL cholesterol levels and in those already receiving a maximal-potency statin in a randomized clinical trial. JAMA Cardiol. 2017;2(12):1385–91. https://doi.org/10.1001/jamacardio.2017.3944.CrossRefPubMedPubMedCentral

91.

Leibowitz M, Cohen-Stavi C, Basu S, Balicer RD. Targeting LDL cholesterol: beyond absolute goals toward personalized risk. Curr Cardiol Rep. 2017;19(6):52. https://doi.org/10.1007/s11886-017-0858-6.CrossRefPubMedPubMedCentral

92.

Humphries SE, Cooper JA, Seed M, Capps N, Durrington PN, Jones B, et al. Coronary heart disease mortality in treated familial hypercholesterolaemia: update of the UK Simon Broome FH register. Atherosclerosis. 2018;274:41–6. https://doi.org/10.1016/j.atherosclerosis.2018.04.040.CrossRefPubMedPubMedCentral

93.

Sabatine MS. PCSK9 inhibitors: clinical evidence and implementation. Nat Rev Cardiol. 2019;16(3):155–65. https://doi.org/10.1038/s41569-018-0107-8.CrossRefPubMed

94.

Kosmas CE, Muñoz Estrella A, Sourlas A, Silverio D, Hilario E, Montan PD, et al. Inclisiran: a new promising agent in the management of hypercholesterolemia. Diseases. 2018;6(3):E63. https://doi.org/10.3390/diseases6030063.CrossRefPubMed

95.

Stoekenbroek RM, Kallend D, Wijngaard PL, Kastelein JJ. Inclisiran for the treatment of cardiovascular disease: the ORION clinical development program. Futur Cardiol. 2018;14(6):433–42. https://doi.org/10.2217/fca-2018-0067.CrossRef

96.

Ray KK, Landmesser U, Leiter LA, Kallend D, Dufour R, Karakas M, et al. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol. N Engl J Med. 2017;376(15):1430–40. https://doi.org/10.1056/NEJMoa1615758.CrossRefPubMed

97.

Leiter LA, Teoh H, Kallend D, Wright RS, Landmesser U, Wijngaard PLJ, et al. Inclisiran lowers LDL-C and PCSK9 irrespective of diabetes status: the ORION-1 randomized clinical trial. Diabetes Care. 2019;42(1):173–6. https://doi.org/10.2337/dc18-1491.CrossRefPubMed

98.

TIMI Study Group. HPS-4/TIMI 65 ORION-4. TIMI.org http://www.timi.org/index.php?page=orion-4 (2018).

99.

Nishikido T, Ray KK. Inclisiran for the treatment of dyslipidemia. Expert Opin Investig Drugs. 2018;27(3):287–94.CrossRefPubMed

100.

Vandrovcova J, Thomas ER, Atanur SS, Norsworthy PJ, Neuwirth C, Tan Y, et al. The use of next-generation sequencing in clinical diagnosis of familial hypercholesterolemia. Genet Med. 2013;15(12):948–57. https://doi.org/10.1038/gim.2013.55.CrossRefPubMed

101.

Norsworthy PJ, Vandrovcova J, Thomas ER, Campbell A, Kerr SM, Biggs J, et al. Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing: a population-based study. BMC Med Genet. 2014;15:70. https://doi.org/10.1186/1471-2350-15-70.CrossRefPubMedPubMedCentral

102.

CDC Office of Public Health Genomics Tier Table Database. Available at: https://phgkb.cdc. gov/PHGKB/topicStartPage.action. Accessed 16 Dec 2018.

103.

National Institute for Health and Care Excellence: clinical guidelines. Available at: https://www.ncbi. nlm.nih.gov/books/NBK11822/. Accessed 18 Dec 2018.

104.

Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, 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;34:3478–90a. https://doi.org/10.1093/eurheartj/eht273.CrossRefPubMedPubMedCentral

105.

Radovica-Spalvina I, Latkovskis G, Silamikelis I, Fridmanis D, Elbere I, Ventins K, et al. Next-generation-sequencing-based identification of familial hypercholesterolemia-related mutations in subjects with increased LDL-C levels in a Latvian population. BMC Med Genet. 2015;16:86. https://doi.org/10.1186/s12881-015-0230-x.CrossRefPubMedPubMedCentral

106.

Hopkins PN, Lane SR. Genotype-guided diagnosis in familial hypercholesterolemia: clinical management and concerns. Curr Opin Lipidol. 2017;28(2):144–51. https://doi.org/10.1097/MOL.0000000000000397.CrossRefPubMed

107.

Marteau T, Senior V, Humphries SE, Bobrow M, Cranston T, Crook MA, et al. Psychological impact of genetic testing for familial hypercholesterolemia within a previously aware population: a randomized controlled trial. Am J Med Genet Part A. 2004;128A:285–93. https://doi.org/10.1002/ajmg.a.30102.CrossRefPubMed

108.

Hallowell N, Jenkins N, Douglas M, Walker S, Finnie R, Porteous M, et al. A qualitative study of patients’ perceptions of the value of molecular diagnosis for familial hypercholesterolemia (FH). J Commun Genet. 2017;8:45–52. https://doi.org/10.1007/s12687-016-0286-0.CrossRef

Titel: Genetics, Dyslipidemia, and Cardiovascular Disease: New Insights
verfasst von: Ricardo Stein
Filipe Ferrari
Fernando Scolari
Publikationsdatum: 01.08.2019
Verlag: Springer US
Erschienen in: Current Cardiology Reports / Ausgabe 8/2019
Print ISSN: 1523-3782
Elektronische ISSN: 1534-3170
DOI: https://doi.org/10.1007/s11886-019-1161-5

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

Genetics, Dyslipidemia, and Cardiovascular Disease: New Insights

Abstract

Purpose of Review

Recent Finding

Summary

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

Abstract

Purpose of Review

Recent Finding

Summary

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

Weitere Artikel der Ausgabe 8/2019

Effect of SGLT2 Inhibitors on the Sympathetic Nervous System and Blood Pressure

New Insights in the Control of Low-Density Lipoprotein Cholesterol to Prevent Cardiovascular Disease

Renal Artery Stenosis and Congestive Heart Failure: What Do We Really Know?

Non-invasive Risk Stratification for Coronary Artery Disease: Is It Time for Subclassifications?

Noninvasive Assessment of Right Ventricular Function in Patients with Pulmonary Arterial Hypertension and Left Ventricular Assist Device

Cardiovascular Sonothrombolysis

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