Skip to main content
Log in

Genes for left ventricular hypertrophy

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Left ventricular (LV) hypertrophy is very common, particularly among hypertensives. The presence of LV hypertrophy profoundly affects morbidity and mortality from cardiovascular diseases and stroke, and is now recognized as the most important predictor of chronic heart failure. Hypertension, obesity, and diabetes are important determinants of LV hypertrophy, but they fail to identify many individuals with the condition, suggesting that other factors, likely genetic in origin, play a role. Although much research has been undertaken to understand the causes of hypertrophy and the medical treatments that can lead to its regression, much remains unknown about its genetic basis. LV hypertrophy is considered a complex genetic disease, likely representing an interaction of several genes with the environment. The heritability of LV mass, measured as a quantitative trait, falls between 0.3 and 0.7 in different populations, suggesting it has a familial component. Genes encoding proteins involved in LV structure, as well as genes encoding cell signal transduction, hormones, growth factors, calcium homeostasis, substrate metabolism, and blood pressure are likely candidates for the development of common forms of LV hypertrophy. An overview of the pathophysiology of LV hypertrophy and dysfunction is provided, in addition to evidence of the genetic basis for LV hypertrophy in humans and animal models.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Koren MJ, Mensah GA, Blake J, et al.: Comparison of left ventricular mass and geometry in black and white patients with essential hypertension. Am J Hypertension 1993, 6:815–823.

    CAS  Google Scholar 

  2. Ghali JK, Liao Y, Cooper RS: Influence of left ventricular geometric patterns on prognosis in patients with or without coronary artery disease. J Am Coll Cardiol 1998, 31:1635–1640.

    Article  PubMed  CAS  Google Scholar 

  3. Gardin JM, Wagenknecht LE, Anton-Culver H, et al.: Relationship of cardiovascular risk factors to echocardiographic left ventricular mass in healthy young black and white adult men and women. The CARDIA study. Coronary Artery Risk Development in Young Adults. Circulation 1995, 923:380–387.

    Google Scholar 

  4. Liebson PR, Grandits G, Prineas R, et al.: Echocardiographic correlates of left ventricular structure among 844 mildly hypertensive men and women in the Treatment of Mild Hypertension Study (TOMHS). Circulation 1993, 87:476–486.

    PubMed  CAS  Google Scholar 

  5. Peltier M, Slama M, Garbi S, et al.: Prognostic value of Doppler-derived myocardial performance index in patients with left ventricular systolic dysfunction. Am J Cardiol 2002, 90:1261–1263.

    Article  PubMed  Google Scholar 

  6. de Simone G, Roman MJ, Koren MJ, et al.: Stroke volume/ pulse pressure ratio and cardiovascular risk in arterial hypertension. Hypertension 1999, 33:800–805.

    PubMed  Google Scholar 

  7. Wang M, Yip GW, Wang AY, et al.: Peak early diastolic mitral annulus velocity by tissue Doppler imaging adds independent and incremental prognostic value. J Am Coll Cardiol 2003, 41:820–826.

    Article  PubMed  Google Scholar 

  8. Lorell BH, Carabello BA: Left ventricular hypertrophy: pathogenesis, detection, and prognosis. Circulation 2000, 102:470–479.

    PubMed  CAS  Google Scholar 

  9. Levy D, Savage DD, Garrison RJ, et al.: Echocardiographic criteria for left ventricular hypertrophy: the Framingham Heart Study. Am J Cardiol 1987, 59:956–960.

    Article  PubMed  CAS  Google Scholar 

  10. Coca A, De la Sierra A: Salt sensitivity and left ventricular hypertrophy. Adv Exper Med Biol 1997, 432:91–101.

    CAS  Google Scholar 

  11. Ganau A, Devereux RB, Pickering TG, et al.: Relation of left ventricular hemodynamic load and contractile performance to left ventricular mass in hypertension. Circulation 1990, 81:25–36.

    PubMed  CAS  Google Scholar 

  12. Galderisi M, Anderson KM, Wilson PWF, Levy D: Echocardiographic evidence for the existence of a distinct diabetic cardiomyopathy the Framingham Heart Study. Am J Cardiol 1991, 68:85–89.

    Article  PubMed  CAS  Google Scholar 

  13. Saba PS, Roman MJ, Pini R, et al.: Relation of carotid pressure waveform to left ventricular anatomy in normotensive subjects. J Am Coll Cardiol 1993, 22:1873–1880.

    Article  PubMed  CAS  Google Scholar 

  14. Lind L, Andersson PE, Andren B, et al.: Left ventricular hypertrophy is associated with the insulin resistance metabolic syndrome. J Hypertens 1995, 13:433–438.

    PubMed  CAS  Google Scholar 

  15. Schroeder AP, Sihm I, Mørn B, et al.: Influence of humoral and neurohormonal factors on cardiovascular hypertrophy in untreated essential hypertensives. Am J Hypertens 1996, 9:207–215.

    Article  PubMed  CAS  Google Scholar 

  16. Schmieder RE, Langenfeld MRW, Friedrich A, Schobel H:Angiotensin II related to sodium excretion modulates left ventricular structure in human essential hypertension. Circulation 1996, 94:1304–1309.

    PubMed  CAS  Google Scholar 

  17. Palmieri V, de Simone G, Arnett DK, et al.: Relation of various degrees of body mass index in patients with systemic hypertension to left ventricular mass, cardiac output, and peripheral resistance (The Hypertension Genetic Epidemiology Network Study). Am J Cardiol 2001, 88:1163–1168.

    Article  PubMed  CAS  Google Scholar 

  18. Scott CL: Diagnosis, prevention, and intervention for the metabolic syndrome. Am J Cardiol 2003, 92(1A):35i-42i.

    Article  PubMed  Google Scholar 

  19. Milani RV, Lavie CJ: Prevalence and profile of metabolic syndrome in patients following acute coronary events and effects of therapeutic lifestyle change with cardiac rehabilitation. Am J Cardiol 2003, 92:50–54.

    Article  PubMed  Google Scholar 

  20. Alexander CM, Landsman PB, Teutsch SM, Haffner SM:Third National Health and Nutrition Examination Survey (NHANES III). National Cholesterol Education Program (NCEP). NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 2003, 52:1210–1214.

    Article  PubMed  CAS  Google Scholar 

  21. Lips DJ, deWindt LJ, van Kraaij DJ, Doevendans PA: Molecular determinants of myocardial hypertrophy and failure: alternative pathways for beneficial and maladaptive hypertrophy. Eur Heart J 2003, 24:883–896.

    Article  PubMed  CAS  Google Scholar 

  22. Bielen E, Fagard R, Amery A: The inheritance of left ventricular structure and function assessed by imaging and Doppler echocardiography. Am Heart J 1991, 21:1743–1749.

    Article  Google Scholar 

  23. Beltrami AP, Urbanek K, Kajstura J, et al.: Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med 2001, 344:1750–1757.

    Article  PubMed  CAS  Google Scholar 

  24. St. John Sutton M, Epstein JA: Hypertrophic cardiomyopathy: beyond the sarcomere. N Engl J Med 1998, 338:1303–1304.

    Article  PubMed  CAS  Google Scholar 

  25. Feldman AM, Weinberg EO, Ray PE, Lorell BH: Selective changes in cardiac gene expression during compensated hypertrophy and the transition to cardiac decompensation in rats with chronic aortic banding. Circ Res 1993, 73:184–192.

    PubMed  CAS  Google Scholar 

  26. Lehman JJ, Kelly DP: Transcriptional activation of energy metabolic switches in the developing and hypertrophied heart. Clin Exp Pharm Physiol 2002, 29:339–345.

    Article  CAS  Google Scholar 

  27. Rucker-Martin C, Pecker F, Godreau D, Hatem SN: Dedifferentiation of atrial myocytes during atrial fibrillation: role of fibroblast proliferation in vitro. Cardiovasc Res 2002, 55:38–52.

    Article  PubMed  CAS  Google Scholar 

  28. Stewart AF, Suzow J, Kubota T, et al.: Transcription factor RTEF-1 mediates alpha1-adrenergic reactivation of the fetal gene program in cardiac myocytes. Circ Res 1998, 83:43–49.

    PubMed  CAS  Google Scholar 

  29. Passier R, Zeng H, Frey N, et al.: CaM kinase signaling induces cardiac hypertrophy and activates the MEF2 transcription factor in vivo. J Clin Invest 2000, 105:1395–1406.

    Article  PubMed  CAS  Google Scholar 

  30. Barger PM, Brandt JM, Leone TC, et al.: Deactivation of peroxisome proliferator-activated receptor-alpha during cardiac hypertrophic growth. J Clin Invest 2000, 105:1723–1730.

    PubMed  CAS  Google Scholar 

  31. Mittmann C, Eschenhagen T, Scholz H: Cellular and molecular aspects of contractile dysfunction in heart failure. Cardiovasc Res 1998, 39:267–275.

    Article  PubMed  CAS  Google Scholar 

  32. Swynghedauw B, Chevalier B, Charlemagne D, et al.: Cardiac hypertrophy, arrhythmogenicity and the new myocardial phenotype. II. The cellular adaptational process. Cardiovasc Res 1997, 35:6–12. Excellent summary of etiology of hypertrophy, particularly related to calcium transport.

    Article  PubMed  CAS  Google Scholar 

  33. Tardif JC, Rouleau JL: Diastolic dysfunction. Can J Cardiol 1996, 12:389–398.

    PubMed  CAS  Google Scholar 

  34. Marian AJ, Roberts R: Familial hypertrophic cardiomyopathy: a paradigm of the cardiac hypertrophic response to injury. Ann Med 1998, 30(Suppl1):24–32. Excellent description of the pathologic process of hypertrophy, and how genetic mutations might cause hypertrophy.

    PubMed  CAS  Google Scholar 

  35. Bonne G, Carrier L, Richard P, et al.: Familial hypertrophic cardiomyopathy: from mutations to functional defects. Circ Res 1998, 83:580–593.

    PubMed  CAS  Google Scholar 

  36. Vikstrom KL, Leinwand LA: Contractile protein mutations and heart disease. Curr Opin Cell Biology 1996, 8:97–105. Provides a comprehensive description of the structure and function of the sarcomeric proteins.

    Article  CAS  Google Scholar 

  37. Flesch M, Schiffer F, Zolk O, et al.: Contractile systolic and diastolic dysfunction in renin-induced hypertensive cardiomyopathy. Hypertension 1997, 30(3 Pt 1):383–391.

    PubMed  CAS  Google Scholar 

  38. Sweeney HL, Feng HS, Yang Z, Watkins H: Functional analyses of troponin T mutations that cause hypertrophic cardiomyopathy: insights into disease pathogenesis and troponin function. Proc Natl Acad Sci U S A 1998, 95:14406–14410.

    Article  PubMed  CAS  Google Scholar 

  39. Niimura H, Bachinski LL, Sangwatanaroj S, et al.: Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy. N Engl J Med 1998, 338:1248–1257.

    Article  PubMed  CAS  Google Scholar 

  40. Solaro RJ, Van Eyk J: Altered interactions among thin filament proteins modulate cardiac function. J Mol Cell Cardiol 1996, 28:217–230.

    Article  PubMed  CAS  Google Scholar 

  41. Roberts R, Sigwart U: New concepts in hypertrophic cardiomyopathies. Part I. Circulation 2001, 104:2113–2116.

    PubMed  CAS  Google Scholar 

  42. Arnett DK, Devereux RB, Kitzman D, et al.: Linkage of left ventricular contractility to chromosome 11 in humans: The HyperGEN Study. Hypertension 2001, 38:767–772.

    PubMed  CAS  Google Scholar 

  43. Kurland L, Melhus H, Karlsson J, et al.: Angiotensin converting enzyme gene polymorphism predicts blood pressure response to angiotensin II receptor type 1 antagonist treatment in hypertensive patients. J Hypertens 2001, 19:1783–1787.

    Article  PubMed  CAS  Google Scholar 

  44. Kurland L, Melhus H, Karlsson J, et al.: Aldosterone synthase (CYP11B2)-344 C/T polymorphism is related to antihypertensive response: result from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial. Am J Hypertens 2002, 15:389–393.

    Article  PubMed  CAS  Google Scholar 

  45. Oberkofler H, Hölzl B, Esterbauer H, et al.: Peroxisome proliferator-activated receptor-gamma coactivator-1 gene locus associations with hypertension in middle-aged men. Hypertension 2003, 41:368–372.

    Article  PubMed  CAS  Google Scholar 

  46. Jamshidi Y, Montgomery HE, Hense HW, et al.: Peroxisome proliferator-activated receptor alpha gene regulates left ventricular growth in response to exercise and hypertension. Circulation 2002, 105:950–955.

    Article  PubMed  CAS  Google Scholar 

  47. de las Fuentes L, Herrero P, Peterson LR, et al.: Myocardial fatty acid metabolism: independent predictor of left ventricular mass in hypertensive heart disease. Hypertension 2003, 41:83–87.

    Article  PubMed  CAS  Google Scholar 

  48. Lander ES, Schork NJ:Genetic dissection of complex traits. Science 1994, 265:2037–2048.

    Article  PubMed  CAS  Google Scholar 

  49. Bing OH, Conrad CH, Boluyt MO, et al.: Studies of prevention, treatment and mechanisms of heart failure in the aging spontaneously hypertensive rat. Heart Fail Rev 2002, 7:71–88.

    Article  PubMed  Google Scholar 

  50. Pomp D: Genetic dissection of obesity in polygenic animal models. Behav Genet 1997, 27:285–306.

    Article  PubMed  CAS  Google Scholar 

  51. Harrap SB, Danes VR, Ellis JA, et al.: The hypertrophic heart rat: a new normotensive model of genetic cardiac and cardiomyocyte hypertrophy. Physiol Genom 2002, 9:43–48.

    Google Scholar 

  52. Tsujita Y, Iwai N, Tamaki S, et al.: Genetic mapping of quantitative trait loci influencing left ventricular mass in rats. Am J Physiol Heart Circ Physiol 2000, 279:H2062-H2067.

    PubMed  CAS  Google Scholar 

  53. Roman RJ, Cowley AW Jr, Greene A, et al.: Consomic rats for the identification of genes and pathways underlying cardiovascular disease. Cold Spring Harb Symp Quant Biol 2002, 67:309–315.

    Article  PubMed  CAS  Google Scholar 

  54. Kwitek AE, Tonellato PJ, Chen D, et al.: Automated construction of high-density comparative maps between rat, human, and mouse. Genome Res 2001, 11:1935–1943.

    PubMed  CAS  Google Scholar 

  55. Stoll M, Kwitek-Black AE, Cowley AW Jr, et al.: New target regions for human hypertension via comparative genomics. Genome Res 2000, 10:473–482.

    Article  PubMed  CAS  Google Scholar 

  56. Pennacchio LA, Rubin EM: Comparative genomic tools and databases: providing insights into the human genome. J Clin Invest 2003, 111:1099–1106.

    Article  PubMed  CAS  Google Scholar 

  57. Loots GG, Locksley RM, Blankespoor CM, et al.: Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons. Science 2000, 288:136–140.

    Article  PubMed  CAS  Google Scholar 

  58. Symula DJ, Frazer KA, Ueda Y, et al.: Functional screening of an asthma QTL in YAC transgenic mice. Nat Genet 1999, 23:241–244.

    Article  PubMed  CAS  Google Scholar 

  59. Thomas JW, Touchman JW, Blakesley RW, et al.: Comparative analyses of multi-species sequences from targeted genomic regions. Nature 2003, 424:788–793.

    Article  PubMed  CAS  Google Scholar 

  60. Liljedahl U, Karlsson J, Melhus H, et al.: A microarray minisequencing system for pharmacogenetic profiling of antihypertensive drug response. Pharmacogenetics 2003, 13:7–17.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arnett, D.K., de las Fuentes, L. & Broeckel, U. Genes for left ventricular hypertrophy. Current Science Inc 6, 36–41 (2004). https://doi.org/10.1007/s11906-004-0009-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-004-0009-5

Keywords

Navigation