Impairment of Arterial Compliance in Cushing’s Syndrome

European Endocrinology, 2014;10(2):161–4 DOI: http://doi.org/10.17925/EE.2014.10.02.161

Abstract:

Arterial stiffness may be useful for stratifying cardiovascular risk in individuals suffering from a number of pathologies, such as hypertension, diabetes, obesity, dyslipidaemia and coronary artery disease. Cushing’s syndrome is underpinned by a complex metabolic syndrome, which is potentially implicated in the onset of blood vessel alterations and the increase in arterial wall stiffness. The aim of this paper was to perform a review about the most important studies conducted in order to evaluate the arterial distensibility profile of subjects affected by Cushing’s syndrome. Increased arterial stiffness may persist even after successful cure of this disease. It is therefore of fundamental importance to identify the presence of early vascular alterations in these patients, in order to commence their treatment and thus attempt to prevent the subsequent onset of adverse cardiovascular events.

Keywords: Arterial stiffness, cardiovascular risk, cardiovascular protection, Cushing
Disclosure: Pier Paolo Bassareo, Angela Maria Zedda and Giuseppe Mercuro have no conflicts of interest to declare. No funding was received for the publication of this article.
Received: May 31, 2013 Accepted August 07, 2014
Correspondence: Pier Paolo Bassareo, Department of Medical Sciences ‘M Aresu’, University of Cagliari, Policlinico Universitario, S.S. 554, bivio di Sestu – 09042 Monserrato, Cagliari, Italy. E: piercard@inwind.it

Arterial Stiffness and Cardiovascular Risk
Recently, much emphasis has been placed on the role of arterial stiffness in the development of cardiovascular diseases. In fact, increased arterial wall rigidity has been acknowledged as a major independent risk factor for cardiovascular pathologies,1,2 and is frequently correlated to the onset of adverse cardiovascular events.3,4 Representing a physiological hallmark of the ageing process, reduced arterial wall distensibility has been also observed in the presence of numerous pathological conditions, including hypertension,5 diabetes,6 obesity,7 dyslipidaemia8 and kidney diseases.9,10 Furthermore, it has been reported how impaired peripheral arterial distensibility may reflect coronary artery endothelial dysfunction as well.11

Indeed, aortic stiffening accompanying age and cardiovascular risk factors is caused by various phenomena, including breaks in elastin fibres, accumulation of collagen, fibrosis, inflammation, medial smooth muscle necrosis, calcifications and diffusion of macromolecules within the arterial wall. All these phenomena are known to occur in parallel at the site of the coronary circulation.

In the light of evidence provided, and of the suitability of non-invasive detection methods, such as photoplethysmography and ultrasonography, this marker of early arterial atherosclerosis is currently increasingly applied in the clinical assessment of patients.12

Search Strategy
A PubMed/Medline search was conducted using the MeSH terms: Cushing’s syndrome, arterial stiffness, arterial compliance, arterial distensibility, intima-media thickness, hypophyseal adenoma, hypophysis, adrenocorticotrope hormone(s), glucocorticoid (GC) hormone(s), cortisol, ultrasound, echography, plethysmography, flow-mediated dilation (FMD), Doppler, cardiac catheterisation, cardiac computed tomography, cardiovascular risk, cardiovascular protection, hypertension, obesity, dyslipidaemia, the metabolic syndrome, endothelial function and their combinations. Articles identified in this manner were retrieved and reference lists searched for additional relevant articles. The search was limited to English-language publications, but no other restrictions were applied. The PubMed/Medline database was searched from its inception to May 2013. The most important of these papers are reported in this review.

Cushing’s Syndrome and Increased Cardiovascular Risk
Cushing’s syndrome is an endocrine disorder more frequent in females (female/male ratio = 8:1). It is characterised by the hypersecretion of cortisol, generally due to the presence of an adenocorticotrope hormone-secreting hypophyseal adenoma. Less common causes are primary adrenal diseases, ectopic adrenocorticotrope hormone secretions and exogenous assumption of corticosteroids .

Cushing’s syndrome is underpinned by a complex metabolic syndrome, which is potentially implicated in the onset of blood vessel alterations and an increase in arterial wall stiffness. The clinical picture is characterised by abdominal obesity, systemic arterial hypertension, impaired glucose metabolism, hyperlipidaemia and hypercoagulation of the blood. Taken together, these factors constitute an ideal substrate for the development of cardiovascular diseases, such as coronary heart disease, stroke and heart failure. Indeed, cardiovascular death in patients with active Cushing’s syndrome is approximately three- or fourfold higher compared with the general population matched for age and gender. Furthermore, untreated Cushing’s syndrome has a poor prognosis, with only a 50 % 5-year survival.13–15

Numerous research projects have demonstrated how the excessive secretion of GC hormones, in particular cortisol, produces a direct effect on the cardiovascular system, leading to both activation of the renin-angiotensin system resulting in sympathetic hypertension, and a reduced release of nitric oxide by the endothelium.16 Although adrenocorticotrope hormones receptors have been demonstrated in human aortic endothelial cells,17 it seems unlikely their direct actions in the development of hypertension in Cushing’s syndrome’s subjects.15

Again, Philips et al.18 have reviewed evidence for the foetal programming of the neuroendocrine response to stress, thus highlighting the correlation of small size at birth with increased adrenocortical and sympatocoadrenal responses.

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Keywords: Arterial stiffness, cardiovascular risk, cardiovascular protection, Cushing