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Three-year change in endothelin-1 and markers of vascular remodelling in a bi-ethnic South African cohort: the SABPA study

Abstract

South Africans are at high risk for developing cardiovascular disease. Endothelin-1 is known for its vasoconstrictive properties and its ability to contribute to vascular structural changes. In this study we investigated the association of change in endothelin-1 levels and change in markers implicated in vascular remodelling after 3 years. Serum endothelin-1 levels and markers of vascular remodelling such as carotid intima-media thickness, carotid cross-sectional wall area (CSWA) and arterial compliance were measured. Participants were divided into two groups according to an increase (n=185) and a decrease (n=152) in plasma endothelin-1 levels after 3 years. In partial regression analysis, the extent of endothelin-1 increase correlated positively with a change in pulse pressure and inversely with the change in arterial compliance in the group with increased endothelin-1 levels after 3 years. In the group with decreased endothelin-1 levels, the extent of decreased endothelin-1 correlated inversely with a change in CSWA. In multiple regression analysis, after splitting for race, the increase in endothelin-1 levels associated positively with the change in pulse pressure (Adj. R2=0.092; β=0.278; P=0.036) in the black participants only. In conclusion, with increased endothelin-1 levels after 3 years, the positive association between endothelin-1 and pulse pressure suggest subclinical haemodynamic changes with potential premature onset of cardiovascular disease in the black participants.

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References

  1. Vita JA, Keaney JF . Endothelial function a barometer for cardiovascular risk? Circulation 2002; 106: 640–642.

    Article  Google Scholar 

  2. Dajnowiec D, Langille BL . Arterial adaptations to chronic changes in haemodynamic function: coupling vasomotor tone to structural remodelling. Clin Sci 2007; 113: 15–23.

    Article  Google Scholar 

  3. Amiri F, Virdis A, Neves MF, Iglarz M, Seidah NG, Touyz RM et al. Endothelium-restricted overexpression of human endothelin-1 causes vascular remodeling and endothelial dysfunction. Circulation 2004; 110: 2233–2240.

    Article  CAS  Google Scholar 

  4. Samijo SK, Willigers JM, Barkhuysen R, Kitslaar P, Reneman RS, Brands PJ et al. Wall shear stress in the human common carotid artery as function of age and gender. Cardiovasc Res 1998; 39: 515–522.

    Article  CAS  Google Scholar 

  5. Schiffrin EL . Endothelin: potential role in hypertension and vascular hypertrophy. Hypertension 1995; 25: 1135–1143.

    Article  CAS  Google Scholar 

  6. Schiffrin EL, Larivière R, Li JS, Sventek P, Touyz RM . Deoxycorticosterone acetate plus salt induces overexpression of vascular endothelin-1 and severe vascular hypertrophy in spontaneously hypertensive rats. Hypertension 1995; 25: 769–773.

    Article  CAS  Google Scholar 

  7. Donato AJ, Gano LB, Eskurza I, Silver AE, Gates PE, Jablonski K et al. Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase. Am J Physiol Heart Circ Physiol 2009; 297: H425–H432.

    Article  CAS  Google Scholar 

  8. Ergul A . Hypertension in black patients: an emerging role of the endothelin system in salt-sensitive hypertension. Hypertension 2000; 36: 62–67.

    Article  CAS  Google Scholar 

  9. Ergul S, Ergul A, Hudson JA, Puett D, Wieman BM, Durham MD et al. The effect of regulation of high blood pressure on plasma endothelin-1 levels in blacks with hypertension. Am J Hypertens 1998; 11: 1381–1385.

    Article  CAS  Google Scholar 

  10. Glasser SP, Arnett DK, McVeigh GE, Finkelstein SM, Bank AK, Morgan DJ et al. The importance of arterial compliance in cardiovascular drug therapy. J Clin Pharmacol 1998; 38: 202–212.

    Article  CAS  Google Scholar 

  11. Ergul A . Endothelin-1 and diabetic complications: focus on the vasculature. Pharmacol Res 2011; 63: 477–482.

    Article  CAS  Google Scholar 

  12. Intengan HD, Schiffrin EL . Structure and mechanical properties of resistance arteries in hypertension role of adhesion molecules and extracellular matrix determinants. Hypertension 2000; 36: 312–318.

    Article  CAS  Google Scholar 

  13. Zanchetti A, Bond MG, Hennig M, Neiss A, Mancia G, Dal Palù C et al. Risk factors associated with alterations in carotid intima—media thickness in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis. J Hypertens 1998; 16: 949–961.

    Article  CAS  Google Scholar 

  14. Schutte AE, Schutte R, Huisman HW, Van Rooyen JM, Fourie CMT, Malan NT et al. Are behavioural risk factors to be blamed for the conversion from optimal blood pressure to hypertensive status in Black South Africans? A 5-year prospective study. Int J Epidemiol 2012; 41: 1114–1123.

    Article  Google Scholar 

  15. American College of Sports Medicine ACSM's Guidelines for Exercise Testing and Prescription. Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2013.

  16. Hayashi I, Morishita Y, Imai K, Nakamura M, Nakachi K, Hayashi T . High-throughput spectrophotometric assay of reactive oxygen species in serum. Mutat Res 2007; 631: 55–61.

    Article  CAS  Google Scholar 

  17. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150: 604–612.

    Article  Google Scholar 

  18. Cockcroft DW, Gault MH . Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31–41.

    Article  CAS  Google Scholar 

  19. O’Brien E, Parati G, Stergiou G, Asmar R, Beilin L, Bilo G et al. European Society of Hypertension position paper on ambulatory blood pressure monitoring. J Hypertens 2013; 31: 1731–1768.

    Article  Google Scholar 

  20. Faul F, Erdfelder E, Buchner A, Lang A-G . Statistical power analyses using G* Power 3.1: Tests for correlation and regression analyses. Behav Res Methods 2009; 41: 1149–1160.

    Article  Google Scholar 

  21. Vuurmans TJ, Boer P, Koomans HA . Effects of endothelin-1 and endothelin-1 receptor blockade on cardiac output, aortic pressure, and pulse wave velocity in humans. Hypertension 2003; 41: 1253–1258.

    Article  CAS  Google Scholar 

  22. Ergul A, Jupin D, Johnson MH, Prisant LM . Elevated endothelin-1 levels are associated with decreased arterial elasticity in hypertensive patients. J Clin Hypertens 2006; 8: 549–554.

    Article  CAS  Google Scholar 

  23. Ergul S, Parish DC, Puett D, Ergul A . Racial differences in plasma endothelin-1 concentrations in individuals with essential hypertension. Hypertension 1996; 28: 652–655.

    Article  CAS  Google Scholar 

  24. Huisman HW, Schutte AE, Schutte R, Van Rooyen JM, Fourie CMT, Mels CMC et al. Exploring the link between cardiovascular reactivity and end-organ damage in African and Caucasian men: the SABPA study. Am J Hypertens 2013; 26: 68–75.

    Article  Google Scholar 

  25. Laurent S . Arterial wall hypertrophy and stiffness in essential hypertensive patients. Hypertension 1995; 26: 355–362.

    Article  CAS  Google Scholar 

  26. Mraiche F, Cena J, Das D, Vollrath B . Effects of statins on vascular function of endothelin-1. Br J Pharmacol 2005; 144: 715–726.

    Article  CAS  Google Scholar 

  27. Schutte AE, Huisman HW, Schutte R, Van Rooyen JM, Malan L, Malan NT et al. Arterial stiffness profiles: investigating various sections of the arterial tree of African and Caucasian people. Clin Exp Hypertens 2011; 33: 511–517.

    Article  Google Scholar 

  28. Schutte AE, Schutte R, Huisman HW, van Rooyen JM, Fourie CMT, Malan NT et al. Blood pressure variability is significantly associated with ECG left ventricular mass in normotensive Africans: the SABPA Study. Hypertens Res 2011; 34: 1127–1134.

    Article  Google Scholar 

  29. du Plooy CS, Mels CMC, Huisman HW, Kruger R . The association of endothelin-1 with markers of oxidative stress in a biethnic South African cohort: the SABPA study. Hypertens Res 2016; 40: 189–195.

    Article  Google Scholar 

  30. Figueiredo VN, Martins LC, Boer-Martins L, de Faria APC, de Haro Moraes C, Santos RC et al. The white coat effect is not associated with additional increase of target organ damage in true resistant hypertension. Med Clin 2013; 140: 1–5.

    Article  Google Scholar 

  31. Treiber FA, Kapuku GK, Davis H, Pollock JS, Pollock DM . Plasma endothelin-1 release during acute stress: role of ethnicity and sex. Psychosom Med 2002; 64: 707–713.

    CAS  PubMed  Google Scholar 

  32. Treiber FA, Barbeau P, Harshfield G, Kang H-S, Pollock DM, Pollock JS et al. Endothelin-1 gene Lys198Asn polymorphism and blood pressure reactivity. Hypertension 2003; 42: 494–499.

    Article  CAS  Google Scholar 

  33. Treiber FA, Kamarck T, Schneiderman N, Sheffield D, Kapuku G, Taylor T . Cardiovascular reactivity and development of preclinical and clinical disease states. Psychosom Med 2003; 65: 46–62.

    Article  Google Scholar 

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Acknowledgements

We thank all SABPA participants, staff, postgraduate students and the Department of Education North-West Province (South Africa) who assisted in the data sampling. The SABPA study was supported by the South African National Research Foundation (UID 65607), the South African National Research Foundation Thuthuka (80643), the North-West University (Potchefstroom Campus, South Africa), Roche Products (Pty), South Africa and the Metabolic Syndrome Institute (France). The financial assistance of the National Research Foundation (NRF SARCHi Postgraduate bursary and DAAD-NRF Joint in-country scholarship (UID 105119)) toward this research study is hereby acknowledged. The funders played no role in the design and conduct of the data. The SABPA study was supported by the South African National Research Foundation (UID 65607), the South African National Research Foundation Thuthuka (80643), the North-West University (Potchefstroom Campus, South Africa), Roche Products (Pty) Ltd, South Africa and the Metabolic Syndrome Institute (France). Christine Susara du Plooy received the financial assistance of the National Research Foundation (NRF SARCHi Postgraduate bursary and DAAD-NRF Joint in-country scholarship (UID 105119)) toward this research study. The funders played no role in the design and conduct of the study.

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Correspondence to R Kruger.

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du Plooy, C., Mels, C., Huisman, H. et al. Three-year change in endothelin-1 and markers of vascular remodelling in a bi-ethnic South African cohort: the SABPA study. J Hum Hypertens 31, 708–714 (2017). https://doi.org/10.1038/jhh.2017.47

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