ORIGINAL ARTICLE Diurnal variation of endothelial function and arterial stiffness in hypertension GE Kollias 1 , KS Stamatelopoulos 1 , TG Papaioannou 1 , NA Zakopoulos 2 , M Alevizaki 3 , GP Alexopoulos 1 , DA Kontoyannis 1 , H Karga 4 , E Koroboki 2 , JP Lekakis 5 and CM Papamichael 1 1 Vascular Laboratory, Department of Clinical Therapeutics, ‘Alexandra’ Hospital, University of Athens Medical School, Athens, Greece; 2 Department of Clinical Therapeutics, Hypertension Clinic, ‘Alexandra’ Hospital, University of Athens Medical School, Athens, Greece; 3 Endocrine Unit, Department of Clinical Therapeutics, ‘Alexandra’ Hospital, University of Athens Medical School, Athens, Greece; 4 Second Division of Endocrinology and Metabolism, ‘Alexandra’ Hospital, University of Athens Medical School, Athens, Greece and 5 Second Department of Cardiology, ‘Attikon’ University Hospital, University of Athens Medical School, Athens, Greece 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%; Po0.001), whereas NMD was similar at the same time points. This difference remained signifi- cant 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 ¼ 0.013 for linear trend). Similar tem- poral 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. Journal of Human Hypertension (2009) 23, 597–604; doi:10.1038/jhh.2009.2; published online 26 February 2009 Keywords: circadian rhythm; endothelium; hypertension; pulse wave velocity; arterial stiffness Introduction Cardiovascular events such as stroke, sudden death and acute myocardial infarction have an increased incidence in the morning 1–5 and a smaller peak in the evening. The mechanisms involved in this variation in cardiovascular events are not clear, and may involve various factors such as augmented sympathetic activation, 6,7 haemodynamic changes, 8 neurohumoral factors and increases in coagulation. 9 Impaired endothelial function and arterial stiffen- ing are associated with increased risk for cardiovas- cular events. 10–12 Recent studies suggest that there is a circadian variation in endothelial function in healthy individuals, with its lowest value in the morning. 13 However, some studies imply that there might be a differentiation of the circadian variation of endothelial function in different conditions 14,15 (for example, menopause) and diseases 16,17 (for example, dilated cardiomyopathy, sleep apnoea), whereas others question the existence of diurnal variation in endothelial function, particularly in populations being at very high risk for cardiovas- cular events. 16,18–21 Thus, it appears that several factors affect the diurnal pattern of endothelial function. Moreover, a circadian variation of arterial stiffness has been demonstrated in healthy subjects indirectly by pulse wave analysis. 22–23 However, this has not been examined in other conditions for which such variations might be more clinically relevant such as in systolic hypertension in which arterial stiffness is considered as one of its most important haemodynamic determinants. 24 Several Received 23 July 2008; revised 16 December 2008; accepted 21 December 2008; published online 26 February 2009 Correspondence: Dr GE Kollias, Vascular Laboratory, Department of Clinical Therapeutics, University of Athens Medical School, Alexandra University Hospital, Vas. Sofias 80, 11528 Athens, Greece. E-mail: giorgoskollias@yahoo.com Journal of Human Hypertension (2009) 23, 597–604 & 2009 Macmillan Publishers Limited All rights reserved 0950-9240/09 $32.00 www.nature.com/jhh