Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Diurnal variation of endothelial function and arterial stiffness in hypertension

Journal of Human Hypertension volume 23, pages 597–604 (2009)Cite this article

Abstract

The onset of cardiovascular events presents a circadian variation that may be mediated by similar temporal patterns of vascular function. Blood pressure also follows circadian variation. We investigated the possible diurnal variation of endothelial function and arterial stiffness in patients with hypertension. Thirty-five individuals with recently diagnosed hypertension (mean age 48.3 years, range 30–60 years, 14 men) were examined. Flow-mediated vasodilatation (FMD), nitrate-mediated vasodilatation (NMD) and carotid–femoral (cf) pulse wave velocity (PWV) were measured at three different occasions: at 0700 hours immediately after awaking, at 1200 hours and at 2100 hours. FMD was markedly lower in the morning (0700 hours, 2.22±1.58%; 1200 hours, 4.37±2.25%; 2100 hours, 4.28±2.12%; P<0.001), whereas NMD was similar at the same time points. This difference remained significant after adjustment for baseline brachial artery diameter and reactive hyperaemia. PWVcf progressively increased from morning to evening (0700 hours, 9.8±1.9 m s−1; 1200 hours, 10.2±2.2 m s−1; 0900 hours, 10.5±1.9 m s−1; P=0.013 for linear trend). Similar temporal patterns were observed in systolic and diastolic blood pressures peaking in the evening. PWVcf changes lost significance after adjustment for changes in mean blood pressure. Endothelial function is decreased in the early morning in hypertensive patients, whereas arterial stiffness is increased in the evening. Changes in BP-dependent passive artery distension may be involved in this phenomenon.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Muller JE, Stone PH, Turi ZG, Rutherford JD, Czeisler CA, Parker C et al. Circadian variation in the frequency of onset of acute myocardial infarction. N Engl J Med 1985; 313: 1315–1322.

    Article  CAS  Google Scholar 

  2. Willich SN, Goldberg RJ, Maclure M, Perriello L, Muller JE . Increased onset of sudden cardiac death in the first three hours after awakening. Am J Cardiol 1992; 70: 65–68.

    Article  CAS  Google Scholar 

  3. Spengos K, Vemmos KN, Tsivgoulis G, Synetos A, Zakopoulos NA, Zis VP et al. Two-peak temporal distribution of stroke onset in Greek patients. A hospital-based study. Cerebrovasc Dis 2003; 15: 70–77.

    Article  Google Scholar 

  4. Stergiou GS, Vemmos KN, Pliarchopoulou KM, Synetos AG, Roussias LG, Mountokalakis TD . Parallel morning and evening surge in stroke onset, blood pressure, and physical activity. Stroke 2002; 33: 1480–1486.

    Article  Google Scholar 

  5. Peters RW, Zoble RG, Liebson PR, Pawitan Y, Brooks MM, Proschan M . Identification of a secondary peak in myocardial infarction onset 11–12 h after awakening: the Cardiac Arrhythmia Suppression Trial (CAST) experience. J Am Coll Cardiol 1993; 22: 998–1003.

    Article  CAS  Google Scholar 

  6. Muller JE, Tofler GH, Verrier RL . Sympathetic activity as the cause of the morning increase in cardiac events: a likely culprit, but the evidence remains circumstantial. Circulation 1995; 91: 2508–2509.

    Article  CAS  Google Scholar 

  7. Hijmering ML, Stroes ES, Olijhoek J, Hutten BA, Blankestijn PJ, Rabelink TJ . Sympathetic activation markedly reduces endothelium-dependent, flow-mediated vasodilation. J Am Coll Cardiol 2002; 39: 683–688.

    Article  Google Scholar 

  8. Panza JA, Epstein SE, Quyyumi AA . Circadian variation in vascular tone and its relation to alpha-sympathetic vasoconstrictor activity. N Engl J Med 1991; 325: 986–990.

    Article  CAS  Google Scholar 

  9. Tofler GH, Brezinski D, Schafer AI, Czeisler CA, Rutherford JD, Willich SN et al. Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death. N Engl J Med 1987; 316: 1514–1518.

    Article  CAS  Google Scholar 

  10. Celermajer DS, Sorensen KE, Bull C, Robinson J, Deanfield JE . Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol 1994; 24: 1468–1474.

    Article  CAS  Google Scholar 

  11. Gokce N, Keaney Jr JF, Hunter LM, Watkins MT, Nedeljkovic ZS, Menzoian JO et al. Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol 2003; 41: 1769–1775.

    Article  Google Scholar 

  12. Oliver JJ, Webb DJ . Noninvasive assessment of arterial stiffness and risk of atherosclerotic events. Arterioscler Thromb Vasc Biol 2003; 23: 554–566.

    Article  CAS  Google Scholar 

  13. Otto ME, Svatikova A, Barretto RB, Santos S, Hoffmann M, Khandheria B et al. Early morning attenuation of endothelial function in healthy humans. Circulation 2004; 109: 2507–2510.

    Article  Google Scholar 

  14. Ringqvist A, Caidahl K, Petersson AS, Wennmalm A . Diurnal variation of flow-mediated vasodilation in healthy premenopausal women. Am J Physiol 2000; 279: H2720–H2725.

    CAS  Google Scholar 

  15. Walters JF, Hampton SM, Deanfield JE, Donald AE, Skene DJ, Ferns GA . Circadian variation in endothelial function is attenuated in postmenopausal women. Maturitas 2006; 54: 294–303.

    Article  CAS  Google Scholar 

  16. Maruo T, Nakatani S, Kanzaki H, Kakuchi H, Yamagishi M, Kitakaze M et al. Circadian variation of endothelial function in idiopathic dilated cardiomyopathy. Am J Cardiol 2006; 97: 699–702.

    Article  CAS  Google Scholar 

  17. Oflaz H, Cuhadaroglu C, Pamukcu B, Meric M, Ece T, Kasikcioglu E et al. Endothelial function in patients with obstructive sleep apnea syndrome but without hypertension. Respiration 2006; 73: 751–756.

    Article  Google Scholar 

  18. Shaw JA, Chin-Dusting JP, Kingwell BA, Dart AM . Diurnal variation in endothelium-dependent vasodilatation is not apparent in coronary artery disease. Circulation 2001; 103: 806–812.

    Article  CAS  Google Scholar 

  19. ter Avest E, Holewijn S, Stalenhoef AF, de Graaf J . Variation in non-invasive measurements of vascular function in healthy volunteers during daytime. Clin Sci (Lond) 2005; 108: 425–431.

    Article  CAS  Google Scholar 

  20. Kawano H, Motoyama T, Yasue H, Hirai N, Waly HM, Kugiyama K et al. Endothelial function fluctuates with diurnal variation in the frequency of ischemic episodes in patients with variant angina. J Am Coll Cardiol 2002; 40: 266–270.

    Article  CAS  Google Scholar 

  21. Elherik K, Khan F, McLaren M, Kennedy G, Belch JJ . Circadian variation in vascular tone and endothelial cell function in normal males. Clin Sci (Lond) 2002; 102: 547–552.

    Article  CAS  Google Scholar 

  22. Papaioannou TG, Karatzis EN, Papamichael CM, Karatzi KN, Zakopoulos NA, Lekakis JP et al. Circadian variation of arterial pressure wave reflections. Am J Hypertens 2006; 19: 259–263.

    Article  Google Scholar 

  23. Bodlaj G, Berg J, Biesenbach G . Diurnal variation of pulse wave velocity assessed non-invasively by applanation tonometry in young healthy men. Yonsei Med J 2007; 48: 665–670.

    Article  Google Scholar 

  24. Safar ME . Pulse pressure, arterial stiffness, and cardiovascular risk. Curr Opin Cardiol 2000; 15: 258–263.

    Article  CAS  Google Scholar 

  25. Kawano H, Motoyama T, Hirashima O, Hirai N, Miyao Y, Sakamoto T et al. Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol 1999; 34: 146–154.

    Article  CAS  Google Scholar 

  26. Mitchell BM, Dorrance AM, Mack EA, Webb RC . Glucocorticoids decrease GTP cyclohydrolase and tetrahydrobiopterin-dependent vasorelaxation through glucocorticoid receptors. J Cardiovasc Pharmacol 2004; 43: 8–13.

    Article  CAS  Google Scholar 

  27. Williams IL, Chowienczyk PJ, Wheatcroft SB, Patel A, Sherwood R, Momin A et al. Effect of fat distribution on endothelial-dependent and endothelial-independent vasodilatation in healthy humans. Diabetes Obes Metab 2006; 8: 296–301.

    Article  CAS  Google Scholar 

  28. Zwaka TP, Hombach V, Torzawski J . C-reactive protein-mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis. Circulation 2001; 103: 1194–1197.

    Article  CAS  Google Scholar 

  29. Staessen JA, Thijs L, Fagard R, O'Brien ET, Clement D, de Leeuw PW et al. Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension: Systolic Hypertension in Europe Trial Investigators. JAMA 1999; 282: 539–546.

    Article  CAS  Google Scholar 

  30. Aznaouridis KA, Stamatelopoulos KS, Karatzis EN, Protogerou AD, Papamichael CM, Lekakis JP . Acute effects of rennin-angiotensin system blockade on arterial function in hypertensive patients. J Hum Hypertens 2007; 21: 654–663.

    Article  CAS  Google Scholar 

  31. Lekakis JP, Protogerou A, Papamichael C, Vamvakou G, Iconomidis I, Fici F et al. Effect of nebivolol and atenolol on brachial artery flow-mediated vasodilation in patients with coronary artery disease. Cardiovasc Drugs Ther 2005; 19: 277–281.

    Article  CAS  Google Scholar 

  32. Mahmud A, Feely J . Effect of angiotensin ii receptor blockade on arterial stiffness: beyond blood pressure reduction. Am J Hypertens 2002; 15: 1092–1095.

    Article  CAS  Google Scholar 

  33. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2007; 28: 1462–1536.

    Google Scholar 

  34. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002; 39: 257–265.

    Article  Google Scholar 

  35. Nichols WW, O'Rourke MF . Properties of the arterial wall. In: Nichols WW, O'Rourke MF (eds). McDonalds' Blood Flow in Arteries. Theoretical, Experimental and Clinical Principles, 5th edn. Oxford University Press Inc.: NY, 2005, pp 80–82.

    Google Scholar 

  36. Van Bortel LM, Duprez D, Starmans-Kool MJ, Safar ME, Giannattasio C, Cockcroft J et al. Clinical applications of arterial stiffness, task force III: recommendations for user procedures. Am J Hypertens 2002; 15: 445–452.

    Article  Google Scholar 

  37. Pietri P, Vyssoulis G, Vlachopoulos C, Zervoudaki A, Gialernios T, Aznaouridis K et al. Relationship between low-grade inflammation and arterial stiffness in patients with essential hypertension. J Hypertens 2006; 24: 2231–2238.

    Article  CAS  Google Scholar 

  38. Conover WJ . Practical Nonparametric Statistics, 3rd edn. Wiley, NY, 1999.

    Google Scholar 

  39. Whitworth JA, Williamson PM, Mangos G, Kelly JJ . Cardiovascular consequences of cortisol excess. Vasc Health Risk Manag 2005; 1: 291–299.

    Article  CAS  Google Scholar 

  40. Kimura Y, Matsumoto M, Den YB, Iwai K, Munehira J, Hattori H et al. Impaired endothelial function in hypertensive elderly patients evaluated by high resolution ultrasonography. Can J Cardiol 1999; 15: 563–568.

    CAS  PubMed  Google Scholar 

  41. London GM . Role of arterial wall properties in the pathogenesis of systolic hypertension. Am J Hypertens 2005; 18: 19S–22S.

    Article  Google Scholar 

  42. Schöfl C, Becker C, Prank K, von zur Mühlen A, Brabant G . Twenty-four-hour rhythms of plasma catecholamines and their relation to cardiovascular parameters in healthy young men. Eur J Endocrinol 1997; 137: 675–683.

    Article  Google Scholar 

  43. Donald AE, Halcox JP, Charakida M, Storry C, Wallace SM, Cole TJ et al. Methodological approaches to optimize reproducibility and power in clinical studies of flow-mediated dilation. J Am Coll Cardiol 2008; 51: 1959–1964.

    Article  Google Scholar 

  44. Hermida RC, Ayala DE, Portaluppi F . Circadian variation of blood pressure: the basis for the chronotherapy of hypertension. Adv Drug Deliv Rev 2007; 59: 904–922.

    Article  CAS  Google Scholar 

  45. Minutolo R, Gabbai FB, Borrelli S, Scigliano R, Trucillo P, Baldanza D et al. Changing the timing of antihypertensive therapy to reduce nocturnal blood pressure in CKD: an 8-week uncontrolled trial. Am J Kidney Dis 2007; 50: 908–917.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Therapeutics, Vascular Laboratory, ‘Alexandra’ Hospital, University of Athens Medical School, Athens, Greece

    G E Kollias, K S Stamatelopoulos, T G Papaioannou, G P Alexopoulos, D A Kontoyannis & C M Papamichael

  2. Department of Clinical Therapeutics, Hypertension Clinic, ‘Alexandra’ Hospital, University of Athens Medical School, Athens, Greece

    N A Zakopoulos & E Koroboki

  3. Department of Clinical Therapeutics, Endocrine Unit, ‘Alexandra’ Hospital, University of Athens Medical School, Athens, Greece

    M Alevizaki

  4. Second Division of Endocrinology and Metabolism, ‘Alexandra’ Hospital, University of Athens Medical School, Athens, Greece

    H Karga

  5. Second Department of Cardiology, ‘Attikon’ University Hospital, University of Athens Medical School, Athens, Greece

    J P Lekakis

Authors
  1. G E Kollias
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K S Stamatelopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T G Papaioannou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N A Zakopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Alevizaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G P Alexopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D A Kontoyannis
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H Karga
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E Koroboki
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J P Lekakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. C M Papamichael
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G E Kollias.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kollias, G., Stamatelopoulos, K., Papaioannou, T. et al. Diurnal variation of endothelial function and arterial stiffness in hypertension. J Hum Hypertens 23, 597–604 (2009). https://doi.org/10.1038/jhh.2009.2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2009.2

Keywords

This article is cited by

Search

Advanced search

Quick links