Skip to main content
PMC home page
Heart logoLink to Heart
. 1997 Jan;77(1):24–31. doi: 10.1136/hrt.77.1.24

Associations between circulating components of the renin-angiotensin-aldosterone system and left ventricular mass.

H Schunkert 1, H W Hense 1, M Muscholl 1, A Luchner 1, S Kürzinger 1, A H Danser 1, G A Riegger 1
PMCID: PMC484630  PMID: 9038690

Abstract

OBJECTIVE: Cardiac growth may be modulated in part by the trophic effects of neurohormones. The aim of the present study was to investigate the relation between the basal activity of the renin-angiotensin-aldosterone system and left ventricular mass. DESIGN: A population based sample of 615 middle-age subjects was studied by standardised echocardiography; anthropometric measurements; and biochemical quantification of renin, pro-renin, angiotensinogen, angiotensin converting enzyme (ACE), and aldosterone. RESULTS: Echocardiographic left ventricular mass index correlated significantly with arterial blood pressure, age, and body mass index. In addition, in men ACE activity was significantly related to left ventricular mass index in univariate (P = 0.0007) and multivariate analyses (P = 0.008). Men with left ventricular hypertrophy presented with significantly higher serum ACE concentrations than those with normal left ventricular mass index (P = 0.002). In both men and women serum aldosterone was strongly related to septal and posterior wall thickness. Furthermore, in women serum aldosterone was positively and independently associated with left ventricular mass index (P = 0.0001). This effect was most prominent in hypertensive women. Finally, women with left ventricular hypertrophy presented with significantly higher serum aldosterone (P = 0.01). No significant associations with left ventricular mass index were observed for angiotensinogen, renin, or pro-renin. CONCLUSIONS: The data suggest that the variability of serum ACE or aldosterone, as occurred in this large population based sample, may contribute to the modulation of left ventricular mass.

Full text

PDF
26

Images in this article

27Image
on p.27
27Image
on p.27

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Badenhop R. F., Wang X. L., Wilcken D. E. Angiotensin-converting enzyme genotype in children and coronary events in their grandparents. Circulation. 1995 Mar 15;91(6):1655–1658. doi: 10.1161/01.cir.91.6.1655. [DOI] [PubMed] [Google Scholar]
  2. Bonithon-Kopp C., Ducimetière P., Touboul P. J., Fève J. M., Billaud E., Courbon D., Héraud V. Plasma angiotensin-converting enzyme activity and carotid wall thickening. Circulation. 1994 Mar;89(3):952–954. doi: 10.1161/01.cir.89.3.952. [DOI] [PubMed] [Google Scholar]
  3. Cambien F., Costerousse O., Tiret L., Poirier O., Lecerf L., Gonzales M. F., Evans A., Arveiler D., Cambou J. P., Luc G. Plasma level and gene polymorphism of angiotensin-converting enzyme in relation to myocardial infarction. Circulation. 1994 Aug;90(2):669–676. doi: 10.1161/01.cir.90.2.669. [DOI] [PubMed] [Google Scholar]
  4. Caulfield M., Newell-Price J. The angiotensin converting enzyme gene in cardiovascular disease. Br Heart J. 1995 Sep;74(3):207–208. doi: 10.1136/hrt.74.3.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Costerousse O., Allegrini J., Lopez M., Alhenc-Gelas F. Angiotensin I-converting enzyme in human circulating mononuclear cells: genetic polymorphism of expression in T-lymphocytes. Biochem J. 1993 Feb 15;290(Pt 1):33–40. doi: 10.1042/bj2900033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Danser A. H., Schalekamp M. A., Bax W. A., van den Brink A. M., Saxena P. R., Riegger G. A., Schunkert H. Angiotensin-converting enzyme in the human heart. Effect of the deletion/insertion polymorphism. Circulation. 1995 Sep 15;92(6):1387–1388. doi: 10.1161/01.cir.92.6.1387. [DOI] [PubMed] [Google Scholar]
  7. Denolle T., Chatellier G., Julien J., Battaglia C., Luo P., Plouin P. F. Left ventricular mass and geometry before and after etiologic treatment in renovascular hypertension, aldosterone-producing adenoma, and pheochromocytoma. Am J Hypertens. 1993 Nov;6(11 Pt 1):907–913. doi: 10.1093/ajh/6.11.907. [DOI] [PubMed] [Google Scholar]
  8. Derkx F. H., Deinum J., Lipovski M., Verhaar M., Fischli W., Schalekamp M. A. Nonproteolytic "activation" of prorenin by active site-directed renin inhibitors as demonstrated by renin-specific monoclonal antibody. J Biol Chem. 1992 Nov 15;267(32):22837–22842. [PubMed] [Google Scholar]
  9. Derkx F. H., de Bruin R. J., van Gool J. M., Rosmalen F. M., van Hoek M. J., Beerendonk C. C., Schalekamp M. A. A novel assay of plasma prorenin using a renin inhibitor. J Hypertens Suppl. 1993 Dec;11(5):S240–S241. [PubMed] [Google Scholar]
  10. Devereux R. B., Koren M. J., de Simone G., Okin P. M., Kligfield P. Methods for detection of left ventricular hypertrophy: application to hypertensive heart disease. Eur Heart J. 1993 Jul;14 (Suppl 500):8–15. doi: 10.1093/eurheartj/14.suppl_d.8. [DOI] [PubMed] [Google Scholar]
  11. Devereux R. B., Pickering T. G., Cody R. J., Laragh J. H. Relation of renin-angiotensin system activity to left ventricular hypertrophy and function in experimental and human hypertension. J Clin Hypertens. 1987 Mar;3(1):87–103. [PubMed] [Google Scholar]
  12. Devereux R. B., Savage D. D., Sachs I., Laragh J. H. Relation of hemodynamic load to left ventricular hypertrophy and performance in hypertension. Am J Cardiol. 1983 Jan 1;51(1):171–176. doi: 10.1016/s0002-9149(83)80031-9. [DOI] [PubMed] [Google Scholar]
  13. Doria A., Warram J. H., Krolewski A. S. Genetic predisposition to diabetic nephropathy. Evidence for a role of the angiotensin I--converting enzyme gene. Diabetes. 1994 May;43(5):690–695. doi: 10.2337/diab.43.5.690. [DOI] [PubMed] [Google Scholar]
  14. Elkik F., Gompel A., Mercier-Bodard C., Kuttenn F., Guyenne P. N., Corvol P., Mauvais-Jarvis P. Effects of percutaneous estradiol and conjugated estrogens on the level of plasma proteins and triglycerides in postmenopausal women. Am J Obstet Gynecol. 1982 Aug 15;143(8):888–892. doi: 10.1016/0002-9378(82)90468-9. [DOI] [PubMed] [Google Scholar]
  15. Ganau A., Devereux R. B., Roman M. J., de Simone G., Pickering T. G., Saba P. S., Vargiu P., Simongini I., Laragh J. H. Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension. J Am Coll Cardiol. 1992 Jun;19(7):1550–1558. doi: 10.1016/0735-1097(92)90617-v. [DOI] [PubMed] [Google Scholar]
  16. Gardin J. M., Siscovick D., Anton-Culver H., Lynch J. C., Smith V. E., Klopfenstein H. S., Bommer W. J., Fried L., O'Leary D., Manolio T. A. Sex, age, and disease affect echocardiographic left ventricular mass and systolic function in the free-living elderly. The Cardiovascular Health Study. Circulation. 1995 Mar 15;91(6):1739–1748. doi: 10.1161/01.cir.91.6.1739. [DOI] [PubMed] [Google Scholar]
  17. Grossman W., Jones D., McLaurin L. P. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest. 1975 Jul;56(1):56–64. doi: 10.1172/JCI108079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Harrap S. B., Davidson H. R., Connor J. M., Soubrier F., Corvol P., Fraser R., Foy C. J., Watt G. C. The angiotensin I converting enzyme gene and predisposition to high blood pressure. Hypertension. 1993 Apr;21(4):455–460. doi: 10.1161/01.hyp.21.4.455. [DOI] [PubMed] [Google Scholar]
  19. Harris E. L., Phelan E. L., Thompson C. M., Millar J. A., Grigor M. R. Heart mass and blood pressure have separate genetic determinants in the New Zealand genetically hypertensive (GH) rat. J Hypertens. 1995 Apr;13(4):397–404. [PubMed] [Google Scholar]
  20. Iwai N., Ohmichi N., Nakamura Y., Kinoshita M. DD genotype of the angiotensin-converting enzyme gene is a risk factor for left ventricular hypertrophy. Circulation. 1994 Dec;90(6):2622–2628. doi: 10.1161/01.cir.90.6.2622. [DOI] [PubMed] [Google Scholar]
  21. Jeunemaitre X., Soubrier F., Kotelevtsev Y. V., Lifton R. P., Williams C. S., Charru A., Hunt S. C., Hopkins P. N., Williams R. R., Lalouel J. M. Molecular basis of human hypertension: role of angiotensinogen. Cell. 1992 Oct 2;71(1):169–180. doi: 10.1016/0092-8674(92)90275-h. [DOI] [PubMed] [Google Scholar]
  22. Kannel W. B., Gordon T., Castelli W. P., Margolis J. R. Electrocardiographic left ventricular hypertrophy and risk of coronary heart disease. The Framingham study. Ann Intern Med. 1970 Jun;72(6):813–822. doi: 10.7326/0003-4819-72-6-813. [DOI] [PubMed] [Google Scholar]
  23. Keil U., Stieber J., Döring A., Chambless L., Härtel U., Filipiak B., Hense H. W., Tietze M., Gostomzyk J. G. The cardiovascular risk factor profile in the study area Augsburg. Results from the first MONICA survey 1984/85. Acta Med Scand Suppl. 1988;728:119–128. doi: 10.1111/j.0954-6820.1988.tb05563.x. [DOI] [PubMed] [Google Scholar]
  24. Krege J. H., John S. W., Langenbach L. L., Hodgin J. B., Hagaman J. R., Bachman E. S., Jennette J. C., O'Brien D. A., Smithies O. Male-female differences in fertility and blood pressure in ACE-deficient mice. Nature. 1995 May 11;375(6527):146–148. doi: 10.1038/375146a0. [DOI] [PubMed] [Google Scholar]
  25. Lauer M. S., Anderson K. M., Kannel W. B., Levy D. The impact of obesity on left ventricular mass and geometry. The Framingham Heart Study. JAMA. 1991 Jul 10;266(2):231–236. [PubMed] [Google Scholar]
  26. Levy D., Anderson K. M., Savage D. D., Kannel W. B., Christiansen J. C., Castelli W. P. Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors. The Framingham Heart Study. Ann Intern Med. 1988 Jan;108(1):7–13. doi: 10.7326/0003-4819-108-1-7. [DOI] [PubMed] [Google Scholar]
  27. Levy D., Garrison R. J., Savage D. D., Kannel W. B., Castelli W. P. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990 May 31;322(22):1561–1566. doi: 10.1056/NEJM199005313222203. [DOI] [PubMed] [Google Scholar]
  28. Lindpaintner K., Lee M., Larson M. G., Rao V. S., Pfeffer M. A., Ordovas J. M., Schaefer E. J., Wilson A. F., Wilson P. W., Vasan R. S. Absence of association or genetic linkage between the angiotensin-converting-enzyme gene and left ventricular mass. N Engl J Med. 1996 Apr 18;334(16):1023–1028. doi: 10.1056/NEJM199604183341604. [DOI] [PubMed] [Google Scholar]
  29. Lindpaintner K., Pfeffer M. A., Kreutz R., Stampfer M. J., Grodstein F., LaMotte F., Buring J., Hennekens C. H. A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med. 1995 Mar 16;332(11):706–711. doi: 10.1056/NEJM199503163321103. [DOI] [PubMed] [Google Scholar]
  30. Lindpaintner K., Sen S. Role of sodium in hypertensive cardiac hypertrophy. Circ Res. 1985 Oct;57(4):610–617. doi: 10.1161/01.res.57.4.610. [DOI] [PubMed] [Google Scholar]
  31. Ludwig E., Corneli P. S., Anderson J. L., Marshall H. W., Lalouel J. M., Ward R. H. Angiotensin-converting enzyme gene polymorphism is associated with myocardial infarction but not with development of coronary stenosis. Circulation. 1995 Apr 15;91(8):2120–2124. doi: 10.1161/01.cir.91.8.2120. [DOI] [PubMed] [Google Scholar]
  32. Marre M., Bernadet P., Gallois Y., Savagner F., Guyene T. T., Hallab M., Cambien F., Passa P., Alhenc-Gelas F. Relationships between angiotensin I converting enzyme gene polymorphism, plasma levels, and diabetic retinal and renal complications. Diabetes. 1994 Mar;43(3):384–388. doi: 10.2337/diab.43.3.384. [DOI] [PubMed] [Google Scholar]
  33. Mattu R. K., Needham E. W., Galton D. J., Frangos E., Clark A. J., Caulfield M. A DNA variant at the angiotensin-converting enzyme gene locus associates with coronary artery disease in the Caerphilly Heart Study. Circulation. 1995 Jan 15;91(2):270–274. doi: 10.1161/01.cir.91.2.270. [DOI] [PubMed] [Google Scholar]
  34. Miyazaki M., Okunishi H., Okamura T., Toda N. Elevated vascular angiotensin converting enzyme in chronic two-kidney, one clip hypertension in the dog. J Hypertens. 1987 Apr;5(2):155–160. doi: 10.1097/00004872-198704000-00005. [DOI] [PubMed] [Google Scholar]
  35. Morgan H. E., Baker K. M. Cardiac hypertrophy. Mechanical, neural, and endocrine dependence. Circulation. 1991 Jan;83(1):13–25. doi: 10.1161/01.cir.83.1.13. [DOI] [PubMed] [Google Scholar]
  36. Nakai K., Itoh C., Miura Y., Hotta K., Musha T., Itoh T., Miyakawa T., Iwasaki R., Hiramori K. Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with serum ACE concentration and increased risk for CAD in the Japanese. Circulation. 1994 Nov;90(5):2199–2202. doi: 10.1161/01.cir.90.5.2199. [DOI] [PubMed] [Google Scholar]
  37. Navarro-Lopez F., Coca A., Pare J. C., De La Sierra A., Bosch X., Urbano Marquez A. Left ventricular hypertrophy in asymptomatic essential hypertension: its relationship with aldosterone and the increase in sodium-proton exchanger activity. Eur Heart J. 1993 Nov;14 (Suppl J):38–41. [PubMed] [Google Scholar]
  38. Ohishi M., Rakugi H., Ogihara T. Association between a deletion polymorphism of the angiotensin-converting-enzyme gene and left ventricular hypertrophy. N Engl J Med. 1994 Oct 20;331(16):1097–1098. doi: 10.1056/NEJM199410203311616. [DOI] [PubMed] [Google Scholar]
  39. Payne M. N., McDonald F., Murray R. G., Bartlett W. A., Jones A. F., Beattie J. M. Plasma angiotensin-converting enzyme activity and carotid wall thickening. Circulation. 1994 Nov;90(5):2566–2568. [PubMed] [Google Scholar]
  40. Powrie J. K., Watts G. F., Ingham J. N., Taub N. A., Talmud P. J., Shaw K. M. Role of glycaemic control in development of microalbuminuria in patients with insulin dependent diabetes. BMJ. 1994 Dec 17;309(6969):1608–1612. doi: 10.1136/bmj.309.6969.1608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rakugi H., Kim D. K., Krieger J. E., Wang D. S., Dzau V. J., Pratt R. E. Induction of angiotensin converting enzyme in the neointima after vascular injury. Possible role in restenosis. J Clin Invest. 1994 Jan;93(1):339–346. doi: 10.1172/JCI116965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Raynolds M. V., Bristow M. R., Bush E. W., Abraham W. T., Lowes B. D., Zisman L. S., Taft C. S., Perryman M. B. Angiotensin-converting enzyme DD genotype in patients with ischaemic or idiopathic dilated cardiomyopathy. Lancet. 1993 Oct 30;342(8879):1073–1075. doi: 10.1016/0140-6736(93)92061-w. [DOI] [PubMed] [Google Scholar]
  43. Rigat B., Hubert C., Alhenc-Gelas F., Cambien F., Corvol P., Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990 Oct;86(4):1343–1346. doi: 10.1172/JCI114844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Rizzoni D., Muiesan M. L., Montani G., Zulli R., Calebich S., Agabiti-Rosei E. Relationship between initial cardiovascular structural changes and daytime and nighttime blood pressure monitoring. Am J Hypertens. 1992 Mar;5(3):180–186. doi: 10.1093/ajh/5.3.180. [DOI] [PubMed] [Google Scholar]
  45. Rowlands D. B., Glover D. R., Ireland M. A., McLeay R. A., Stallard T. J., Watson R. D., Littler W. A. Assessment of left-ventricular mass and its response to antihypertensive treatment. Lancet. 1982 Feb 27;1(8270):467–470. doi: 10.1016/s0140-6736(82)91448-9. [DOI] [PubMed] [Google Scholar]
  46. Ruiz J., Blanché H., Cohen N., Velho G., Cambien F., Cohen D., Passa P., Froguel P. Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is strongly associated with coronary heart disease in non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3662–3665. doi: 10.1073/pnas.91.9.3662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Sahn D. J., DeMaria A., Kisslo J., Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation. 1978 Dec;58(6):1072–1083. doi: 10.1161/01.cir.58.6.1072. [DOI] [PubMed] [Google Scholar]
  48. Schunkert H., Dzau V. J., Tang S. S., Hirsch A. T., Apstein C. S., Lorell B. H. Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation. J Clin Invest. 1990 Dec;86(6):1913–1920. doi: 10.1172/JCI114924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Schunkert H., Hense H. W., Holmer S. R., Stender M., Perz S., Keil U., Lorell B. H., Riegger G. A. Association between a deletion polymorphism of the angiotensin-converting-enzyme gene and left ventricular hypertrophy. N Engl J Med. 1994 Jun 9;330(23):1634–1638. doi: 10.1056/NEJM199406093302302. [DOI] [PubMed] [Google Scholar]
  50. Schunkert H., Ingelfinger J. R., Hirsch A. T., Pinto Y., Remme W. J., Jacob H., Dzau V. J. Feedback regulation of angiotensin converting enzyme activity and mRNA levels by angiotensin II. Circ Res. 1993 Feb;72(2):312–318. doi: 10.1161/01.res.72.2.312. [DOI] [PubMed] [Google Scholar]
  51. Schunkert H., Ingelfinger J. R., Hirsch A. T., Tang S. S., Litwin S. E., Talsness C. E., Dzau V. J. Evidence for tissue-specific activation of renal angiotensinogen mRNA expression in chronic stable experimental heart failure. J Clin Invest. 1992 Oct;90(4):1523–1529. doi: 10.1172/JCI116020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Schunkert H., Sadoshima J., Cornelius T., Kagaya Y., Weinberg E. O., Izumo S., Riegger G., Lorell B. H. Angiotensin II-induced growth responses in isolated adult rat hearts. Evidence for load-independent induction of cardiac protein synthesis by angiotensin II. Circ Res. 1995 Mar;76(3):489–497. doi: 10.1161/01.res.76.3.489. [DOI] [PubMed] [Google Scholar]
  53. Simpson P. Norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha 1 adrenergic response. J Clin Invest. 1983 Aug;72(2):732–738. doi: 10.1172/JCI111023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Sullivan J. M., Vander Zwaag R. V., el-Zeky F., Ramanathan K. B., Mirvis D. M. Left ventricular hypertrophy: effect on survival. J Am Coll Cardiol. 1993 Aug;22(2):508–513. doi: 10.1016/0735-1097(93)90057-8. [DOI] [PubMed] [Google Scholar]
  55. Tiret L., Ricard S., Poirier O., Arveiler D., Cambou J. P., Luc G., Evans A., Nicaud V., Cambien F. Genetic variation at the angiotensinogen locus in relation to high blood pressure and myocardial infarction: the ECTIM Study. J Hypertens. 1995 Mar;13(3):311–317. [PubMed] [Google Scholar]
  56. Tiret L., Rigat B., Visvikis S., Breda C., Corvol P., Cambien F., Soubrier F. Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet. 1992 Jul;51(1):197–205. [PMC free article] [PubMed] [Google Scholar]
  57. Weber K. T., Brilla C. G. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation. 1991 Jun;83(6):1849–1865. doi: 10.1161/01.cir.83.6.1849. [DOI] [PubMed] [Google Scholar]

Articles from Heart are provided here courtesy of BMJ Publishing Group

RESOURCES