ORIGINAL ARTICLE High pulse pressure is not associated with abnormal activation of the renin–angiotensin–aldosterone system in repaired aortic coarctation TAL Pedersen 1,2 , EB Pedersen 3 , K Munk 2 , VE Hjortdal 1 , K Emmertsen 2 and NH Andersen 2 We investigated the relationship between pulse pressure (PP)—a surrogate marker of arterial stiffness—and activity of the renin–angiotensin–aldosterone system (RAAS) in adult patients with repaired coarctation and normal left ventricular (LV) function. A total of 114 patients (44 (26–74) years, 13 (0.1–40) years at repair) and 20 healthy controls were examined with 24-h ambulatory blood pressure monitoring, echocardiography, vasoactive hormone levels and magnetic resonance of the thoracic aorta. Forty-one patients (36%) were taking antihypertensives (28 RAAS inhibitors). Fifty-one had mean 24-h blood pressures 4130/80 mm Hg. Hypertension was not associated with age at repair (P = 0.257). Patients had higher PP and LV mass compared with controls (52 ± 11 vs 45 ± 5 mm Hg and 221 ± 71 vs 154 ± 55 g, respectively; both P o0.05). Differences were more pronounced in the presence of recoarctation, but independently of RAA levels. Even normotensive patients had higher LV mass than controls. LV mass and recoarctation were correlated with PP levels. In conclusion, adult patients with repaired coarctation have increased PP and LV mass compared with controls. PP increased with increasing recoarctation. Hypertension was present also in the absence of recoarctation. These changes could not be explained by abnormal activation of the RAAS. Journal of Human Hypertension advance online publication, 28 August 2014; doi:10.1038/jhh.2014.75 INTRODUCTION Repaired aortic coarctation (CoA) is associated with high long-term mortality and morbidity. 1,2 Persistent left ventricular (LV) hypertrophy, myocardial dysfunction and particularly arterial hypertension are common features even among patients with no residual arch obstruction (ReCoA). 3,4 The pathogenesis of the persistent late morbidity in the absence of a mechanical substrate is not fully understood. Previous studies have shown that changes in arterial compliance and wave reflections are likely involved in the underlying pathophysiological mechanisms of hypertension. 5,6 Abnormal activation of the renin–angiotensin–aldosterone system (RAAS) in CoA-related hypertension and cardiovascular morbidity has also been proposed, but results have been conflicting. 7–10 Increased arterial stiffness has been demonstrated in patients with repaired CoA. 11,12 However, traditional measure- ments of arterial stiffness, such as pulse wave velocity, distensi- bility and augmentation indexes, often require complex approaches and trained observers. 13 A much simpler and readily obtainable surrogate measure of arterial stiffness, which easily can be applied in clinical practice, is pulse pressure (PP). 14 Some studies have identified elevated PP as a predictor of cardiovascular risk in different patient subgroups, 15–17 as well as in the general population. 18,19 However, the conclusive role of PP as a risk marker is not fully settled. It is possible that reduced arterial compliance may reflect the adverse vascular effects of abnormal activity of the RAAS. Collagen degradation, smooth muscle proliferation and vascular remodelling leading to fibrosis are seen in both increased arterial stiffness and RAAS-associated vascular damage. 20,21 Data relating the activity of the RAAS to arterial stiffness, particularly in the CoA population, are far from complete. The aim of this study was therefore to investigate the relationship between PP and activity of RAAS and in adult patients with repaired CoA and normal LV systolic function. MATERIALS AND METHODS Study participants During 1965–1985, 246 patients underwent surgical repair of CoA in our institution, as previously described. 2 All 156 survivors were invited to participate in this study, and 133 accepted study participation (examina- tion was conducted between 2008 and 2010). Nine did not complete the 24-h ambulatory blood pressure monitoring (ABPM) and were excluded. A further six were excluded due to more than trivial aortic valve regurgitation, three due to severe heart failure (LV ejection fraction ⩽ 40%) 18 and one due to clinically overt coronary heart disease. The study population thus comprised 114 patients. Median age was 44 (26–74) years, median body mass index 26 (16–39) kg m -2 and median body surface area = 1.9 (1.3–2.6) m 2 . Twenty normotensive gender and age-matched healthy controls (11 males, body mass index = 23 (19–29) kg m -2 , body surface area = 1.9 (1.6–2.2) m 2 ) with a median age of 40 (25–64) years were recruited by written announcement (poster) placed at the hospital’s surrounding districts. Twenty-four-hour ambulatory blood pressure measurements and PP calculations Twenty-four-hour ABPM was recorded on the right upper arm every 15 min during daytime and every 30 min during diary-registered nighttime using a 1 Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, Denmark; 2 Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark and 3 Departments of Medical Research and Medicine, Holstebro Hospital, Holstebro, Denmark. Correspondence: Dr TAL Pedersen, Department of Cardiology, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark. E-mail: thais.a.pedersen@ki.au.dk Received 11 March 2014; revised 10 June 2014; accepted 16 June 2014 Journal of Human Hypertension (2014), 1 – 6 © 2014 Macmillan Publishers Limited All rights reserved 0950-9240/14 www.nature.com/jhh