Skip to main content

Advertisement

SpringerLink
Log in

Pharmacogenetics of Heart Failure: Evidence, Opportunities, and Challenges for Cardiovascular Pharmacogenomics

  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

Heart failure is a significant medical problem affecting more than five million people in the USA alone. Although clinical trials of pharmacological agents have demonstrated significant reductions in the relative risk of mortality across populations, absolute mortality remains high. In addition, individual variation in response is great. Some of this variation may be explained by genetic polymorphism. In this paper, we review the key studies to date in heart failure pharmacogenetics, setting this against a background of recent progress in the genetics of warfarin metabolism. Several polymorphisms that have supporting molecular and clinical data in the heart failure literature are reviewed, among them the β1-adrenergic receptor variant Arg389Gly and the angiotensin converting enzyme gene insertion/deletion polymorphism. These variants and others are responsible for a fraction of the total variation seen in the treatment response to heart failure. With the dawn of the genomic age, further pharmacogenetic and new pharmacogenomic studies will advance our ability to tailor the treatment of heart failure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Rosamond W., Flegal K., Friday G., Furie K., Go A., Greenlund K., et al. (2007). Update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation, 115(5), e69–e171, (February 6).

    Article  PubMed  Google Scholar 

  2. Lloyd-Jones D. M., Larson M. G., LeipE. P., Beiser A., D’Agostino R. B., Kannel W. B., et al. (2002). Lifetime risk for developing congestive heart failure: The Framingham Heart Study. Circulation, 106(24), 3068–243072, (Dec 10).

    Article  PubMed  Google Scholar 

  3. Pitt B., Zannad F., Remme W. J., Cody R., Castaigne A., Perez A., et al. (1999). The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. New England Journal of Medicine, 341(10), 709–717, (Sep 2).

    Article  PubMed  CAS  Google Scholar 

  4. Packer M., Fowler M. B., Roecker E. B., Coats A. J., Katus H. A., Krum H., et al. (2002). Effect of carvedilol on the morbidity of patients with severe chronic heart failure: Results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation, 106(17), 2194–2199, (Oct 22).

    Article  PubMed  Google Scholar 

  5. Hjalmarson A., Goldstein S., Fagerberg B., Wedel H., Waagstein F., Kjekshus J., et al. (2000). Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: The Metoprolol CR/XL randomized intervention trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group. JAMA, 283(10), 1295–101302, (Mar 8).

    Article  PubMed  CAS  Google Scholar 

  6. Konstam M. A., Rousseau M. F., Kronenberg M. W., Udelson J. E., Melin J., Stewart D., et al. (1992). Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dysfunction in patients with heart failure. SOLVD Investigators. Circulation, 86(2), 431–438, (Aug).

    PubMed  CAS  Google Scholar 

  7. Investigators T. S. (1991). Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. New England Journal of Medicine, 325(5), 293–302, (Aug 1).

    Article  Google Scholar 

  8. Roger V. L., Weston S. A., Redfield M. M., Hellermann-Homan J. P., Killian J., Yawn B. P., et al. (2004). Trends in heart failure incidence and survival in a community-based population. JAMA, 292(3), 344–350, (Jul 21).

    Article  PubMed  CAS  Google Scholar 

  9. Thomas K. L., East M. A., Velazquez E. J., Tuttle R. H., Shaw L. K., O'Connor C. M., et al. (2005). Outcomes by race and etiology of patients with left ventricular systolic dysfunction. American Journal of Cardiology, 96(7), 956–963. (Oct 1).

    Article  PubMed  Google Scholar 

  10. Follath F., Cleland J. G., Klein W., Murphy R. (1998). Etiology and response to drug treatment in heart failure. Journal of the American College of Cardiology, 32(5), 1167–1172, (Nov).

    Article  PubMed  CAS  Google Scholar 

  11. Owan T. E., Hodge D. O., Herges R. M., Jacobsen S. J., Roger V. L., Redfield M. M. (2006). Trends in prevalence and outcome of heart failure with preserved ejection fraction. New England Journal of Medicine, 355(3), 251–259, (Jul 20).

    Article  PubMed  CAS  Google Scholar 

  12. Tabibiazar R., Wagner R. A., Deng A., Tsao P. S., Quertermous T. (2006). Proteomic profiles of serum inflammatory markers accurately predict atherosclerosis in mice. Physiological Genomics, 25(2), 194–202, (Apr 13).

    Article  PubMed  CAS  Google Scholar 

  13. King J. Y., Ferrara R., Tabibiazar R., Spin J. M., Chen M. M., Kuchinsky A., et al. (2005). Pathway analysis of coronary atherosclerosis. Physiological Genomics, 23(1), 103–118, (Sep 21).

    Article  PubMed  CAS  Google Scholar 

  14. Alizadeh A. A., Eisen M. B., Davis R. E., Ma C., Lossos I. S., Rosenwald A., et al. (2000). Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature, 403(6769), 503–511, (Feb 3).

    Article  PubMed  CAS  Google Scholar 

  15. Arnett D. K., Baird A. E., Barkley R. A., Basson C. T., Boerwinkle E., Ganesh S. K., et al. (2007). Relevance of genetics and genomics for prevention and treatment of cardiovascular disease: A scientific statement from the American Heart Association Council on Epidemiology and Prevention, the Stroke Council, and the Functional Genomics and Translational Biology Interdisciplinary Working Group. Circulation, 115(22), 2878–2901, (Jun 5).

    Article  PubMed  Google Scholar 

  16. Davies, S. M. (2006). Pharmacogenetics, pharmacogenomics and personalized medicine: Are we there yet? Hematology Am Soc Hematol Educ Program, pp. 111–117.

  17. Consortium I. H. G. S. (2004). Finishing the euchromatic sequence of the human genome. Nature, 431(7011), 931–945, (Oct 21).

    Article  CAS  Google Scholar 

  18. Lander E. S., Linton L. M., Birren B., Nusbaum C., Zody M. C., Baldwin J., et al. (2001). Initial sequencing and analysis of the human genome. Nature, 409(6822), 860–921, (Feb 15).

    Article  PubMed  CAS  Google Scholar 

  19. Frazer K. A., Ballinger D. G., Cox D. R., Hinds D. A., Stuve L. L., Gibbs R. A., et al. (2007). A second generation human haplotype map of over 3.1 million SNPs. Nature, 449(7164), 851–861, (Oct 18).

    Article  PubMed  CAS  Google Scholar 

  20. Cupples L. A., Arruda H. T., Benjamin E. J., D'Agostino R. B. Sr., Demissie S., DeStefano A. L., et al. (2007). The Framingham heart study 100K SNP genome-wide association study resource: Overview of 17 phenotype working group reports. BMC Medical Genetics, 8, Suppl 1S1.

    Article  PubMed  CAS  Google Scholar 

  21. Saxena R., Voight B. F., Lyssenko V., Burtt N. P., de Bakker P. I., Chen H., et al. (2007). Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science, 316(5829), 1331–1336, (Jun 1).

    Article  PubMed  CAS  Google Scholar 

  22. Gudbjartsson D. F., Arnar D. O., Helgadottir A., Gretarsdottir S., Holm H., Sigurdsson A., et al. (2007) Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature, 448(7151), 353–357, (Jul 19).

    Article  PubMed  CAS  Google Scholar 

  23. Horne B. D., Carlquist J. F., Muhlestein J. B., Nicholas Z. P., Anderson J. L. (2007) Associations with myocardial infarction of six polymorphisms selected from a three-stage genome-wide association study. American Heart Journal, 154(5), 969–975, (Nov).

    Article  PubMed  CAS  Google Scholar 

  24. Higashi M. K., Veenstra D. L., Kondo L. M., Wittkowsky A. K., Srinouanprachanh S. L., Farin F. M., et al. (2002). Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA, 287(13), 1690–1698, (Apr 3).

    Article  PubMed  CAS  Google Scholar 

  25. Sanderson S., Emery J., Higgins J. (2005). CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: A HuGEnet systematic review and meta-analysis. Genetics in Medicine, 7(2), 97–104, (Feb).

    Article  PubMed  CAS  Google Scholar 

  26. Li T., Chang C. Y., Jin D. Y., Lin P. J., Khvorova A., Stafford D. W. (2004) Identification of the gene for vitamin K epoxide reductase. Nature, 427(6974), 541–544, (Feb 5).

    Article  PubMed  CAS  Google Scholar 

  27. Rost S., Fregin A., Ivaskevicius V., Conzelmann E., Hortnagel K., Pelz H. J., et al. (2004). Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature, 427(6974), 537–541, (Feb 5).

    Article  PubMed  CAS  Google Scholar 

  28. Rieder M. J., Reiner A. P., Gage B. F., Nickerson D. A., Eby C. S., McLeod H. L., et al. (2005). Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. New England Journal of Medicine, 352(22), 2285–2293, (Jun 2).

    Article  PubMed  CAS  Google Scholar 

  29. Takahashi H., Wilkinson G. R., Nutescu E. A., Morita T., Ritchie M. D., Scordo M. G., et al. (2006). Different contributions of polymorphisms in VKORC1 and CYP2C9 to intra- and inter-population differences in maintenance dose of warfarin in Japanese, Caucasians and African-Americans. Pharmacogenetics & Genomics, 16(2), 101–110, (Feb).

    Article  CAS  Google Scholar 

  30. Aquilante C. L., Langaee T. Y., Lopez L. M., Yarandi H. N., Tromberg J. S., Mohuczy D., Gaston K. L., et al. (2006). Influence of coagulation factor, vitamin K epoxide reductase complex subunit 1, and cytochrome P450 2C9 gene polymorphisms on warfarin dose requirements. Clinical Pharmacology and Therapeutics, 79(4), 291–302, (Apr).

    Article  PubMed  CAS  Google Scholar 

  31. Carlquist J. F., Horne B. D., Muhlestein J. B., Lappe D. L., Whiting B. M., Kolek M. J. (2006). Genotypes of the cytochrome p450 isoform, CYP2C9, and the vitamin K epoxide reductase complex subunit 1 conjointly determine stable warfarin dose: A prospective study. Journal of Thrombosis and Thrombolysis, 22(3), 191–197, (Dec).

    Article  PubMed  CAS  Google Scholar 

  32. Kimura R., Miyashita K., Kokubo Y., Akaiwa Y., Otsubo R., Nagatsuka K., et al. (2007). Genotypes of vitamin K epoxide reductase, gamma-glutamyl carboxylase, and cytochrome P450 2C9 as determinants of daily warfarin dose in Japanese patients. Thrombosis Research, 120(2), 181–186.

    Article  PubMed  CAS  Google Scholar 

  33. Herman D., Peternel P., Stegnar M., Breskvar K., Dolzan V., (2006). The influence of sequence variations in factor VII, gamma-glutamyl carboxylase and vitamin K epoxide reductase complex genes on warfarin dose requirement. Thrombosis and Haemostasis, 95(5), 782–787, (May).

    PubMed  CAS  Google Scholar 

  34. Anderson, J. L., Horne, B. D., Stevens, S. M., Grove, A. S., Barton, S., Nicholas, Z. P., et al. (2007). Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation. Circulation, 116, 2563–2570.

    Google Scholar 

  35. Baudhuin L. M., Langman L. J., O'Kane D. J., (2007). Translation of pharmacogenetics into clinically relevant testing modalities. Clinical Pharmacology and Therapeutics, 82(4), 373–376, (Oct).

    Article  PubMed  CAS  Google Scholar 

  36. Rettie A. E., Tai G., (2006). The pharmocogenomics of warfarin: Closing in on personalized medicine. Molecular Interventions, 6(4), 223–227, (Aug).

    Article  PubMed  CAS  Google Scholar 

  37. Wadelius M., Pirmohamed M. (2007). Pharmacogenetics of warfarin: Current status and future challenges. Pharmacogenomics Journal, 7(2), 99–111, (Apr).

    Article  PubMed  CAS  Google Scholar 

  38. Knowles J. W., Assimes T. L., Li J., Quertermous T., Cooke J. P. (2007). Genetic susceptibility to peripheral arterial disease: A dark corner in vascular biology. Arteriosclerosis, Thrombosis, and Vascular Biology, 27(10), 2068–2078, (Oct).

    Article  PubMed  CAS  Google Scholar 

  39. Arnett D. K., (2007). Summary of the American Heart Association’s scientific statement on the relevance of genetics and genomics for prevention and treatment of cardiovascular disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 27(8), 1682–1686, (Aug).

    Article  PubMed  CAS  Google Scholar 

  40. Wang W. Y., Barratt B. J., Clayton D. G., Todd J. A. (2005). Genome-wide association studies: Theoretical and practical concerns. Nature Reviews. Genetics, 6(2), 109–118, (Feb).

    Article  PubMed  CAS  Google Scholar 

  41. Klein T. E., Chang J. T., Cho M. K., Easton K. L., Fergerson R., Hewett M., et al. (2001). Integrating genotype and phenotype information: An overview of the PharmGKB project. Pharmacogenetics Research Network and Knowledge Base. Pharmacogenomics Journal, 1(3), 167–170.

    PubMed  CAS  Google Scholar 

  42. Patsopoulos N. A., Tatsioni A., Ioannidis J. P. (2007). Claims of sex differences: an empirical assessment in genetic associations. JAMA, 298(8), 880–893.

    Article  PubMed  CAS  Google Scholar 

  43. Ioannidis J. P., (2007). Non-replication and inconsistency in the genome-wide association setting. Human Heredity, 64(4), 203–213.

    Article  PubMed  CAS  Google Scholar 

  44. Takekuma Y., Takenaka T., Kiyokawa M., Yamazaki K., Okamoto H., Kitabatake A., et al. (2007). Evaluation of effects of polymorphism for metabolic enzymes on pharmacokinetics of carvedilol by population pharmacokinetic analysis. Biological & Pharmaceutical Bulletin, 30(3), 537–542, (Mar).

    Article  CAS  Google Scholar 

  45. Ismail R., Teh L. K., (2006). The relevance of CYP2D6 genetic polymorphism on chronic metoprolol therapy in cardiovascular patients. Journal of Clinical Pharmacy and Therapeutics, 31(1), 99–109, (Feb).

    Article  PubMed  CAS  Google Scholar 

  46. Kirchheiner J., Heesch C., Bauer S., Meisel C., Seringer A., Goldammer M., et al. (2004). Impact of the ultrarapid metabolizer genotype of cytochrome P450 2D6 on metoprolol pharmacokinetics and pharmacodynamics. Clinical Pharmacology and Therapeutics, 76(4), 302–312, (Oct).

    PubMed  CAS  Google Scholar 

  47. Cascorbi I., Paul M., Kroemer H. K., (2004). Pharmacogenomics of heart failure—focus on drug disposition and action. Cardiovascular Research, 64(1), 32–39, (Oct 1).

    Article  PubMed  CAS  Google Scholar 

  48. Kolek M. J., Carlquist J. F., Thaneemit-Chen S., Lazzeroni L. C., Whiting B. M., Horne B. D., et al. (2005) The role of a common adenosine monophosphate deaminase (AMPD)-1 polymorphism in outcomes of ischemic and nonischemic heart failure. Journal of Cardiac Failure, 11(9), 677–683, (Dec).

    Article  PubMed  CAS  Google Scholar 

  49. Yazaki Y., Muhlestein J. B., Carlquist J. F., Bair T. L., Horne B. D., Renlund D. G., (2004). A common variant of the AMPD1 gene predicts improved survival in patients with ischemic left ventricular dysfunction. Journal of Cardiac Failure, 10(4), 316–320, (Aug).

    Article  PubMed  CAS  Google Scholar 

  50. de Groote P., Lamblin N., Helbecque N., Mouquet F., Hermant X., et al. (2006). The impact of the AMPD1 gene polymorphism on exercise capacity, other prognostic parameters, and survival in patients with stable congestive heart failure: A study in 686 consecutive patients. American Heart Journal, 152(4), 736–741, (Oct).

    Article  PubMed  CAS  Google Scholar 

  51. Kalsi K. K., Yuen A. H., Rybakowska I. M., Johnson P. H., Slominska E., Birks E. J., (2003). Decreased cardiac activity of AMP deaminase in subjects with the AMPD1 mutation—a potential mechanism of protection in heart failure. Cardiovascular Research, 59(3), 678–684, (Sep 1).

    Article  PubMed  CAS  Google Scholar 

  52. McNamara D. M., Holubkov R., Postava L., Ramani R., Janosko K., Mathier M., et al. (2003). Effect of the Asp298 variant of endothelial nitric oxide synthase on survival for patients with congestive heart failure. Circulation, 107(12), 1598–1602, (Apr 1).

    Article  PubMed  CAS  Google Scholar 

  53. dbSNP. (2007). dbSNP accession: rs180252, rs1801253, rs1042711, rs17858183, rs 17859732, rs1800888.

  54. Maqbool A., Hall A. S., Ball S. G., Balmforth A. J., (1999). Common polymorphisms of beta1-adrenoceptor: identification and rapid screening assay. Lancet, 353(9156), 897, (Mar 13).

    Article  PubMed  CAS  Google Scholar 

  55. Mialet Perez J., Rathz D. A., Petrashevskaya N. N., Hahn H. S., Wagoner L. E., Schwartz A., et al. (2003). Beta 1-adrenergic receptor polymorphisms confer differential function and predisposition to heart failure. Natural Medicines, 9(10), 1300–1305, (Oct).

    Article  CAS  Google Scholar 

  56. Rochais F., Vilardaga J. P., Nikolaev V. O., Bunemann M., Lohse M. J., Engelhardt S., (2007). Real-time optical recording of beta1-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedilol. Journal of Clinical Investigation, 117(1), 229–235, (Jan).

    Article  PubMed  CAS  Google Scholar 

  57. Wagoner L. E., Craft L. L., Zengel P., McGuire N., Rathz D. A., Dorn G. W. 2nd, et al. (2002). Polymorphisms of the beta1-adrenergic receptor predict exercise capacity in heart failure. American Heart Journal, 144(5), 840–846, (Nov).

    PubMed  CAS  Google Scholar 

  58. White H. L., de Boer R. A., Maqbool A., Greenwood D., van Veldhuisen D. J., Cuthbert R., et al. (2003). An evaluation of the beta-1 adrenergic receptor Arg389Gly polymorphism in individuals with heart failure: A MERIT-HF sub-study. European Journal of Heart Failure, 5(4), 463–468, (Aug).

    Article  PubMed  CAS  Google Scholar 

  59. Liggett S. B., Mialet-Perez J., Thaneemit-Chen S., Weber S. A., Greene S. M., Hodne D., (2006). A polymorphism within a conserved beta(1)-adrenergic receptor motif alters cardiac function and beta-blocker response in human heart failure. Proceedings of the National Academy of Sciences of the United States of America, 103(30), 11288–11293, (Jul 25).

    Article  PubMed  CAS  Google Scholar 

  60. Liggett S. B., Wagoner L. E., Craft L. L., Hornung R. W., Hoit B. D., McIntosh T. C., et al. (1998). The Ile164 beta2-adrenergic receptor polymorphism adversely affects the outcome of congestive heart failure. Journal of Clinical Investigation, 102(8), 1534–1539.

    Article  PubMed  CAS  Google Scholar 

  61. Leineweber K., Tenderich G., Wolf C., Wagner S., Zittermann A., Elter-Schulz M., et al. (2006). Is there a role of the Thr164Ile-beta(2)-adrenoceptor polymorphism for the outcome of chronic heart failure?. Basic Research in Cardiology, 101(6), 479–484, (Nov).

    Article  PubMed  CAS  Google Scholar 

  62. Kaye D. M., Smirk B., Williams C., Jennings G., Esler M., Holst D., (2003). Beta-adrenoceptor genotype influences the response to carvedilol in patients with congestive heart failure. Pharmacogenetics, 13(7), 379–382, (Jul).

    Article  PubMed  CAS  Google Scholar 

  63. Forleo C., Resta N., Sorrentino S., Guida P., Manghisi A., De Luca V., et al. (2004). Association of beta-adrenergic receptor polymorphisms and progression to heart failure in patients with idiopathic dilated cardiomyopathy. American Journal of Medicine, 117(7), 451–458, (Oct 1).

    Article  PubMed  CAS  Google Scholar 

  64. Forleo C., Sorrentino S., Guida P., Romito R., De Tommasi E., Iacoviello M., et al. (2007). Beta1- and beta2-adrenergic receptor polymorphisms affect susceptibility to idiopathic dilated cardiomyopathy. Journal of Cardiovascular Medicine (Hagerstown), 8(8), 589–595, (Aug).

    Article  Google Scholar 

  65. de Groote P., Lamblin N., Helbecque N., Mouquet F., Mc Fadden E., Hermant X., et al. (2005). The impact of beta-adrenoreceptor gene polymorphisms on survival in patients with congestive heart failure. European Journal of Heart Failure, 7(6), 966–973.

    Article  PubMed  CAS  Google Scholar 

  66. de Groote P., Helbecque N., Lamblin N., Hermant X., Mc Fadden E., Foucher-Hossein C., et al. (2005). Association between beta-1 and beta-2 adrenergic receptor gene polymorphisms and the response to beta-blockade in patients with stable congestive heart failure. Pharmacogenetics & Genomics, 15(3), 137–142, (Mar).

    Google Scholar 

  67. Small K. M., Wagoner L. E., Levin A. M., Kardia S. L., Liggett S. B., (2002). Synergistic polymorphisms of beta1- and alpha2C-adrenergic receptors and the risk of congestive heart failure. New England Journal of Medicine, 347(15), 1135–1142, (Oct 10).

    Article  PubMed  CAS  Google Scholar 

  68. Regitz-Zagrosek V., Hocher B., Bettmann M., Brede M., Hadame kK., Gerstner C., et al. (2006). Alpha2C-adrenoceptor polymorphism is associated with improved event-free survival in patients with dilated cardiomyopathy. European Heart Journal, 27(4), 454–459, (Feb).

    Article  PubMed  Google Scholar 

  69. Hasimu B., Nakayama T., Mizutani Y., Izumi Y., Asai S., Soma M., et al. (2003). Haplotype analysis of the human renin gene and essential hypertension. Hypertension, 41(2), 308–312, (Feb).

    Article  PubMed  CAS  Google Scholar 

  70. Goldbergova M., Spinarova L., Spinar J., Toman J., Vasku A., Vacha J., (2003). Association of two angiotensinogen gene polymorphisms, M235T and G(-6)A, with chronic heart failure. International Journal of Cardiology, 89(2–3), 267–272, (Jun).

    PubMed  Google Scholar 

  71. Diez J., Laviades C., Orbe J., Zalba G., Lopez B., Gonzalez A., et al. (2003). The A1166C polymorphism of the AT1 receptor gene is associated with collagen type I synthesis and myocardial stiffness in hypertensives. Journal De L’hypertension, 21(11), 2085–2092, (Nov).

    Article  CAS  Google Scholar 

  72. Cameron V. A., Mocatta T. J., Pilbrow A. P., Frampton C. M., Troughton R. W., Richards A. M., et al. (2006). Angiotensin type-1 receptor A1166C gene polymorphism correlates with oxidative stress levels in human heart failure. Hypertension, 47(6), 1155–1161, (Jun).

    Article  PubMed  CAS  Google Scholar 

  73. Hindorff L. A., Heckbert S. R., Tracy R., Tang Z., Psaty B. M., Edwards K. L., et al. (2002). Angiotensin II type 1 receptor polymorphisms in the cardiovascular health study: relation to blood pressure, ethnicity, and cardiovascular events. American Journal of Hypertension, 15(12), 1050–1056, (Dec).

    Article  PubMed  CAS  Google Scholar 

  74. Pitt B., Remme W., Zannad F., Neaton J., Martinez F., Roniker B., et al. (2003). Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. New England Journal of Medicine, 348(14), 1309–1321, (Apr 3).

    Article  PubMed  CAS  Google Scholar 

  75. McNamara D. M., Tam S. W., Sabolinski M. L., Tobelmann P., Janosko K., Taylor A. L., (2006). Aldosterone synthase promoter polymorphism predicts outcome in African Americans with heart failure: Results from the A-HeFT Trial. Journal of the American College of Cardiology, 48(6), 1277–1282, (Sep 19).

    Article  PubMed  CAS  Google Scholar 

  76. Tiago A. D., Badenhorst D., Skudicky D., Woodiwiss A. J., Candy G. P., BrooksbankR., et al. (2002). An aldosterone synthase gene variant is associated with improvement in left ventricular ejection fraction in dilated cardiomyopathy. Cardiovascular Research, 54(3), 584–589, (Jun).

    Article  PubMed  CAS  Google Scholar 

  77. Montgomery H. E., Keeling P. J., Goldman J. H., Humphries S. E., Talmud P. J., McKenna W. J., (1995). Lack of association between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and idiopathic dilated cardiomyopathy. Journal of the American College of Cardiology, 25(7), 1627–1631, (Jun).

    Article  PubMed  CAS  Google Scholar 

  78. Andersson B., Sylven C., (1996). The DD genotype of the angiotensin-converting enzyme gene is associated with increased mortality in idiopathic heart failure. Journal of the American College of Cardiology, 28(1), 162–167, (Jul).

    Article  PubMed  CAS  Google Scholar 

  79. Covolo L., Gelatti U., Metra M., Donato F., Nodari S., Pezzali N., et al. (2003). Angiotensin-converting-enzyme gene polymorphism and heart failure: A case-control study. Biomarkers, 8(5), 429–436, (Sep–Oct).

    Article  PubMed  CAS  Google Scholar 

  80. Schut A. F., Bleumink G. S., Stricker B. H., Hofman A., Witteman J. C., PolsH. A., (2004). Angiotensin converting enzyme insertion/deletion polymorphism and the risk of heart failure in hypertensive subjects. European Heart Journal, 25(23), 2143–2148, (Dec).

    Article  PubMed  CAS  Google Scholar 

  81. Cicoira M., Zanolla L., Rossi A., Golia G., Franceschini L., Cabrini G., et al. (2001). Failure of aldosterone suppression despite angiotensin-converting enzyme (ACE) inhibitor administration in chronic heart failure is associated with ACE DD genotype. Journal of the American College of Cardiology, 37(7), 1808–1812, (Jun 1).

    Article  PubMed  CAS  Google Scholar 

  82. Tang W. H., Vagelos R. H., Yee Y. G., Fowler M. B., (2004). Impact of angiotensin-converting enzyme gene polymorphism on neurohormonal responses to high- versus low-dose enalapril in advanced heart failure. American Heart Journal, 148(5), 889–894, (Nov).

    Article  PubMed  CAS  Google Scholar 

  83. McNamara D. M., Holubkov R., Postava L., Janosko K., MacGowan G. A., Mathier M., et al. (2004). Pharmacogenetic interactions between angiotensin-converting enzyme inhibitor therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure. Journal of the American College of Cardiology, 44(10), 2019–2026, (Nov 16).

    Article  PubMed  CAS  Google Scholar 

  84. Cicoira M., Rossi A., Bonapace S., Zanolla L., Perrot A., FrancisD. P., (2004). Effects of ACE gene insertion/deletion polymorphism on response to spironolactone in patients with chronic heart failure. American Journal of Medicine, 116(10), 657–661, (May 15).

    Article  PubMed  CAS  Google Scholar 

  85. McNamara D. M., Holubkov R., Janosko K., Palmer A., Wang J. J., MacGowan G. A., et al. (2001). Pharmacogenetic interactions between beta-blocker therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure. Circulation, 103(12), 1644–1648, (Mar 27).

    PubMed  CAS  Google Scholar 

  86. de Groote P., Helbecque N., Lamblin N., Hermant X., Amouyel P., Bauters C., et al. (2004). Beta-adrenergic receptor blockade and the angiotensin-converting enzyme deletion polymorphism in patients with chronic heart failure. European Journal of Heart Failure, 6(1), 17–21, (Jan).

    Article  PubMed  CAS  Google Scholar 

  87. Danser A. H., Batenburg W. W., van den Meiracker A. H., Danilov S. M. (2007). ACE phenotyping as a first step toward personalized medicine for ACE inhibitors. Why does ACE genotyping not predict the therapeutic efficacy of ACE inhibition?. Pharmacology & Therapeutics, 113(3), 607–618, (Mar).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Medicine, Stanford University, 300 Pasteur Drive, Falk CVRC MC 5406, Stanford, CA, 94305, USA

    Matthew T. Wheeler, Michael Ho, Joshua W. Knowles, Aleks Pavlovic & Euan A. Ashley

Authors
  1. Matthew T. Wheeler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joshua W. Knowles
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aleks Pavlovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Euan A. Ashley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Euan A. Ashley.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wheeler, M.T., Ho, M., Knowles, J.W. et al. Pharmacogenetics of Heart Failure: Evidence, Opportunities, and Challenges for Cardiovascular Pharmacogenomics. J. of Cardiovasc. Trans. Res. 1, 25–36 (2008). https://doi.org/10.1007/s12265-007-9007-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-007-9007-8

Keywords

Search

Navigation