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The interplay between renin-angiotensin system activation, abnormal myocardial deformation and neurohumoral activation in hypertensive heart disease: a speckle tracking echocardiography study

  • Ignatios Ikonomidis
  • Stavros Tzortzis
  • Argirios Tsantes
  • Konstantina Ntai
  • Helen Triantafyllidi
  • Paraskevi Trivilou
  • George Katsimaglis
  • Kleanthi Dima
  • John Parissis
  • John Lekakis
Original Paper

Abstract

Angiotensin converting enzyme (ACE) promotes cardiac fibrosis. LV myocardial deformation and torsion are markers of subclinical myocardial dysfunction. We investigated the association of serum ACE levels with LV deformation markers in untreated hypertensives. In 120 untreated patients (age: 53.5 ± 11.2 years) with essential hypertension and 60 healthy controls, we measured (a) LV longitudinal, circumferential and radial strain (S), peak torsion and the percentage changes between peak twisting and untwisting at the end of early diastolic filling (%dpTw-UtwEDF) using speckle tracking echocardiography and (b) serum levels of ACE and NTproBNP. Compared to controls, patients had decreased longitudinal strain (−19.1 ± 2.9 vs. −21.7 ± 1.8%), increased peak twisting (19.1 ± 4.6 vs.14.0 ± 3.7 deg) but decreased %dpTw-UtwEDF (78 ± 8 vs. 86 ± 8%) and higher serum ACE levels (27.6 ± 8.0 vs 20.9 ± 7.1 U/ml) (p < 0.05 for all comparisons). Increasing serum ACE levels were related to impaired radial strain and longitudinal systolic SR (b = −0.41 and b = 0.31 respectively, p < 0.01), as well as to reduced %dpTw-UtwEDF (b = −0.37, p < 0.05). Furthermore, increasing serum ACE levels were related to increasing NTproBNP levels (b = 0.41, p < 0.01). In multivariate analysis, the above relations of serum ACE levels and LV function parameters remained significant after adjustment for other confounding factors (p < 0.01). The close link between serum ACE levels and impaired LV deformation suggests that activation of renin-angiotensin system is involved in the impairment of LV function resulting in elevated LV filling pressures causing the concomitant elevation of BNP levels in untreated hypertensive patients.

Keywords

Serum ACE levels LV deformation Fibrosis 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Gonzalez A, Lopez B, Diez J (2004) Fibrosis in hypertensive heart disease role of the angiotensin–aldosterone system. Med Clin North Am 88:83–97CrossRefPubMedGoogle Scholar
  2. 2.
    Leitman M, Lysyansky P, Sidenko S, Shir V, Peleg E, Binenbaum M, Kaluski E, Krakover R, Vered Z (2004) Two-dimensional strain—a novel software for real-time quantitative echocardiographic assessment of myocardial function. J Am Soc Echocardiogr 17:1021–1029CrossRefPubMedGoogle Scholar
  3. 3.
    Reisner SA, Lysyansky P, Agmon Y, Mutlak D, Lessick J, Friedman Z (2004) Global longitudinal strain: a novel index of left ventricular systolic function. J Am Soc Echocardiogr 17:630–633CrossRefPubMedGoogle Scholar
  4. 4.
    Helle-Valle T, Crosby J, Edvardsen T, Lyseggen E, Amundsen BH, Smith HJ, Rosen BD, Lima JA, Torp H, Ihlen H, Smiseth OA (2005) New non-invasive method for assessment of left ventricular rotation: speckle tracking echocardiography. Circulation 112:3149–3156CrossRefPubMedGoogle Scholar
  5. 5.
    Takeuchi M, Borden WB, Nakai H, Nishikage T, Kokumai M, Nagakura T, Otani S, Lang RM (2007) Reduced and delayed untwisting of the left ventricle in patients with hypertension and left ventricular hypertrophy: a study using two-dimensional speckle tracking imaging. Eur Heart J 28:2756–2762CrossRefPubMedGoogle Scholar
  6. 6.
    Pavlopoulos H, Grapsa J, Stefanadi E, Philippou E, Dawson D, Nihoyannopoulos P (2008) Is it only diastolic dysfunction? Segmental relaxation patterns and longitudinal systolic deformation in systemic hypertension. Eur J Echocardiogr 9:741–747CrossRefPubMedGoogle Scholar
  7. 7.
    Poulsen SH (2005) Relation between plasma aminoterminal propeptide of procollagen type III and left ventricular longitudinal strain in essential hypertension. Heart 91:624–629CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Ikonomidis I, Lekakis J, Papadopoulos C, Triantafyllidi H, Paraskevaidis I, Georgoula G, Tzortzis S, Revela I, Kremastinos DT (2008) Incremental value of pulse wave velocity in the determination of coronary microcirculatory dysfunction in never-treated patients with essential hypertension. Am J Hypertens 21:806–813CrossRefPubMedGoogle Scholar
  9. 9.
    Thomas JD, Popovic ZB (2006) Assessment of left ventricular function by cardiac ultrasound. J Am Coll Cardiol 48:2012–2025CrossRefPubMedGoogle Scholar
  10. 10.
    Ikonomidis I, Tzortzis S, Andreadou I, Paraskevaidis I, Katseli C, Katsimbri P, Pavlidis G, Parissis J, Kremastinos D, Anastasiou-Nana M, Lekakis J (2014) Increased benefit of interleukin 1 inhibition on vascular function, myocardial deformation, and twisting in patients with coronary artery disease and coexisting rheumatoid arthritis. Circ Cardiovasc Imaging 7:619–628CrossRefPubMedGoogle Scholar
  11. 11.
    Perk G, Tunick PA, Kronzon I (2007) Non-Doppler two-dimensional strain imaging by echocardiography-from technical considerations to clinical applications. J Am Soc Echocardiogr 20:234–243CrossRefPubMedGoogle Scholar
  12. 12.
    Erdogan D, Yildirim I, Ciftci O, Ozer I, Caliskan M, Gullu H, Muderrisoglu H (2007) Effects of normal blood pressure, prehypertension, and hypertension on coronary microvascular function. Circulation 115:593–599CrossRefPubMedGoogle Scholar
  13. 13.
    Kang SJ, Lim HS, Choi BJ, Choi SY, Hwang GS, Yoon MH, Tahk SJ, Shin JH (2008) Longitudinal strain and torsion assessed by two-dimensional speckle tracking correlate with the serum level of tissue inhibitor of matrix metalloproteinase-1, a marker of myocardial fibrosis, in patients with hypertension. J Am Soc Echocardiogr 21:907–911CrossRefPubMedGoogle Scholar
  14. 14.
    Notomi Y, Lysyansky P, Setser RM, Shiota T, Popović ZB, Martin-Miklovic MG, Weaver JA, Oryszak SJ, Greenberg NL, White RD, Thomas JD (2005) Measurement of ventricular torsion by two-dimensional ultrasound speckle tracking imaging. J Am Coll Cardiol 45:2034–2041CrossRefPubMedGoogle Scholar
  15. 15.
    Raptis AE, Markakis KP, Mazioti MC, Ikonomidis I, Maratou EP, Vlahakos DV, Kotsifaki EE, Voumvourakis AN, Tsirogianni AG, Lambadiari VA, Lekakis JP, Raptis SA, Dimitriadis GD (2015) Effect of aliskiren on circulating endothelial progenitor cells and vascular function in patients with type 2 diabetes and essential hypertension. Am J Hypertens 28:22–29CrossRefPubMedGoogle Scholar
  16. 16.
    Cuspidi C, Ciulla M, Zanchetti A (2006) Hypertensive myocardial fibrosis. Nephrol Dial Transplant 21:20–23CrossRefPubMedGoogle Scholar
  17. 17.
    Diez J, Lopez B, Gonzales A, Querejeta R (2001) Clinical aspects of hypertensive myocardial fibrosis. Curr Opin Cardiol 16:328–335CrossRefPubMedGoogle Scholar
  18. 18.
    González A, López B, Querejeta R, Díez J (2002) Regulation of myocardial fibrillar collagen by angiotensin II. A role in hypertensive heart disease? J Mol Cell Cardiol 34:1585–1593CrossRefPubMedGoogle Scholar
  19. 19.
    Rossi MA (1998) Pathologic fibrosis and connective tissue matrix in left ventricular hypertrophy due to chronic arterial hypertension in humans. J Hypertens 16:1031–1041CrossRefPubMedGoogle Scholar
  20. 20.
    Olivetti G, Melissari M, Balbi T, Quaini F, Cigola E, Sonnenblick EH, Anversa P (1994) Myocyte cellular hypertrophy is responsible for ventricular remodelling in the hypertrophic heart of middle aged individuals in the absence of heart failure. Cardiovasc Res 28:1199–1208CrossRefPubMedGoogle Scholar
  21. 21.
    Ciulla M, Paliotti R, Hess DB, Tjahja E, Campbell SE, Magrini F, Weber KT (1997) Echocardiographic patterns of myocardial fibrosis in hypertensive patients: endomyocardial biopsy versus ultrasonic tissue characterization. J Am Soc Echocardiogr 10:657–664CrossRefPubMedGoogle Scholar
  22. 22.
    Sengupta PP, Krishnamoorthy VK, Korinek J, Narula J, Vannan MA, Lester SJ, Tajik JA, Seward JB, Khandheria BK, Belohlavek M (2007) Left ventricular form and function revisited: applied translational science to cardiovascular ultrasound imaging. J Am Soc Echocardiogr 20:539–551CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Sengupta PP, Khandheria BK, Korinek J, Wang J, Jahangir A, Seward JB, Belohlavek M (2006) Apex-to-base dispersion in regional timing of left ventricular shortening and lengthening. J Am Coll Cardiol 47:163–172CrossRefPubMedGoogle Scholar
  24. 24.
    Wang J, Khoury DS, Yue Y, Torre-Amione G, Nagueh SF (2007) Left ventricular untwisting rate by speckle tracking echocardiography. Circulation 116:2580–2586CrossRefPubMedGoogle Scholar
  25. 25.
    Youn HJ, Ihm SH, Lee JM, Park CS, Cho EJ, Jung HO, Jeon HK, Oh YS, Chung WS, Kim JH, Choi KB, Hong SJ (2006) Relation between flow reserve capacity of penetrating intramyocardial coronary arteries and myocardial fibrosis in hypertension: study using transthoracic Doppler echocardiography. J Am Soc Echocardiogr 19:373–378CrossRefPubMedGoogle Scholar
  26. 26.
    Ikonomidis I, Tzortzis S, Papaioannou T, Protogerou A, Stamatelopoulos K, Papamichael C, Zakopoulos N, Lekakis J (2008) Incremental value of arterial wave reflections in the determination of left ventricular diastolic dysfunction in untreated patients with essential hypertension. J Hum Hypertens 22:687–698CrossRefPubMedGoogle Scholar
  27. 27.
    Mottram P, Haluska B, Leano R, Carlier S, Case C, Marwick T (2005) Relation of arterial stiffness to diastolic dysfunction in hypertensive heart disease. Heart 91:1551–1556CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Yano M, Kohno M, Kobayashi S, Obayashi M, Seki K, Ohkusa T, Miura T, Fujii T, Matsuzaki M (2001) Influence of timing and magnitude of arterial wave reflection on left ventricular relaxation. Am J Physiol Heart Circ Physiol 280:H1846–H1852PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Ignatios Ikonomidis
    • 1
  • Stavros Tzortzis
    • 1
  • Argirios Tsantes
    • 1
  • Konstantina Ntai
    • 1
  • Helen Triantafyllidi
    • 1
  • Paraskevi Trivilou
    • 1
  • George Katsimaglis
    • 1
  • Kleanthi Dima
    • 1
  • John Parissis
    • 1
  • John Lekakis
    • 1
  1. 1.2nd Cardiology Department, Attikon HospitalUniversity of AthensAthensGreece

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