Horm Metab Res 2017; 49(03): 214-220
DOI: 10.1055/s-0043-100385
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Ambulatory Arterial Stiffness Indexes in Cushing’s Syndrome

Marialberta Battocchio*
1   Department of Medicine-DIMED, University of Padova, Padova, Italy
,
Andrea Rebellato*
1   Department of Medicine-DIMED, University of Padova, Padova, Italy
,
Andrea Grillo
2   Department of Medical, Surgical and Healthy Sciences, University of Trieste, Trieste, Italy
,
Francesca Dassie
1   Department of Medicine-DIMED, University of Padova, Padova, Italy
,
Pietro Maffei
1   Department of Medicine-DIMED, University of Padova, Padova, Italy
,
Stella Bernardi
2   Department of Medical, Surgical and Healthy Sciences, University of Trieste, Trieste, Italy
,
Bruno Fabris
2   Department of Medical, Surgical and Healthy Sciences, University of Trieste, Trieste, Italy
,
Renzo Carretta
2   Department of Medical, Surgical and Healthy Sciences, University of Trieste, Trieste, Italy
,
Francesco Fallo
1   Department of Medicine-DIMED, University of Padova, Padova, Italy
› Author Affiliations
Further Information

Publication History

received 10 October 2016

accepted 22 December 2016

Publication Date:
22 February 2017 (online)

Abstract

Long-standing exposure to endogenous cortisol excess is associated with high cardiovascular risk. The aim of our study was to investigate arterial stiffness, which has been recognized as an independent predictor of adverse cardiovascular outcome, in a group of patients with Cushing’s syndrome. Twenty-four patients with Cushing’s syndrome (3 males, mean age 49±13 years; 20 pituitary-dependent Cushing’s disease and 4 adrenal adenoma) underwent 24-h ambulatory blood pressure monitoring (ABPM) and evaluation of cardiovascular risk factors. The Ambulatory Arterial Stiffness Index (AASI) and symmetric AASI (sAASI) were derived from ABPM tracings. Cushing patients were divided into 8 normotensive (NOR-CUSH) and 16 hypertensive (HYP-CUSH) patients, and were compared with 8 normotensive (NOR-CTR) and 16 hypertensive (HYP-CTR) control subjects, matched for demographic characteristics, 24-h ABPM and cardiometabolic risk factors. The AASI and sAASI indexes were significantly higher in Cushing patients than in controls, either in the normotensive (p=0.048 for AASI and p=0.013 for sAASI) or in the hypertensive (p=0.004 for AASI and p=0.046 for sAASI) group. No difference in metabolic parameters was observed between NOR-CUSH and NOR-CTR or between HYP-CUSH and HYP-CTR groups. AASI and sAASI were both correlated with urinary cortisol in patients with endogenous hypercortisolism (Spearman’s rho=0.40, p=0.05, and 0.61, p=0.003, respectively), while no correlation was found in controls. Both AASI and sAASI are increased in Cushing syndrome, independent of BP elevation, and may represent an additional cardiovascular risk factor in this disease. The role of excess cortisol in arterial stiffness has to be further clarified.

* MB and AR contributed equally to this work


 
  • References

  • 1 Boscaro M, Barzon L, Fallo F, Sonino N. Cushing’s syndrome. Lancet 2001; 357: 783-791
  • 2 Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP, Fava GA, Findling JW, Gaillard RC, Grossman AB, Kola B, Lacroix A, Mancini T, Mantero F, Newell-Price J, Nieman LK, Sonino N, Vance ML, Giustina A, Boscaro M. Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 2003; 88: 5593-5602
  • 3 Pivonello R, Faggiano A, Lombardi G, Colao A. The metabolic syndrome and the cardiovascular risk in Cushing’s syndrome. Endocrinol Metab Clin North Am 2005; 34: 327-339
  • 4 Fallo F, Sonino N. Should we evaluate for cardiovascular disease in patients with Cushing’s syndrome?. Clin Endocrinol (Oxf) 2009; 71: 768-771
  • 5 Ferraù F, Korbonits M. Metabolic comorbidities in Cushing’s syndrome. Eur J Endocrinol 2015; 173: M133-M157
  • 6 Baykan M, Erem C, Gedikli O, Hacihasanoglu A, Erdogan T, Kocak M, Durmuş I, Korkmaz L, Celik S. Impairment of flow-mediated vasodilatation of brachial artery in patients with Cushing’s syndrome. Endocrine 2007; 31: 300-304
  • 7 Colao A, Pivonello R, Spiezia S, Faggiano A, Ferone D, Filippella M, Marzullo P, Cerbone G, Siciliani M, Lombardi G. Persistence of increased cardiovascular risk in patients with Cushing’s disease after five years of successful cure. J Clin Endocrinol Metab 1999; 84: 2664-2672
  • 8 Albiger N, Testa RM, Almoto B, Ferrari M, Bilora F, Petrobelli F, Pagnan A, Mantero F, Scaroni C. Patients with Cushing’s syndrome have increased intimal media thickness at different vascular levels: comparison with a population matched for similar cardiovascular risk factors. Horm Metab Res 2006; 38: 405-410
  • 9 Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H. European network for non-invasive investigation of large arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006; 27: 2588-2605
  • 10 Li Y, Wang JG, Dolan E, Gao PJ, Guo HF, Nawrot T, Stanton AV, Zhu DL, O’Brien E, Staessen JA. Ambulatory arterial stiffness index derived from 24-hour ambulatory blood pressure monitoring. Hypertension 2006; 47: 359-364
  • 11 Gavish B, Ben-Dov IZ, Bursztyn M. Linear relationship between systolic and diastolic blood pressure monitored over 24 h: assessment and correlates. J Hypertens 2008; 26: 199-209
  • 12 Dassie F, Grillo A, Carretta R, Fabris B, Macaluso L, Bardelli M, Martini C, Paoletta A, Vettor R, Sicolo N, Fallo F, Maffei P. Ambulatory arterial stiffness indexes in acromegaly. Eur J Endocrinol 2012; 166: 199-205
  • 13 Dolan E, Thijs L, Li Y, Atkins N, McCormack P, McClory S, O’Brien E, Staessen JA, Stanton AV. Ambulatory arterial stiffness index as a predictor of cardiovascular mortality in the Dublin Outcome Study. Hypertension 2006; 47: 365-370
  • 14 Kikuya M, Staessen JA, Ohkubo T, Thijs L, Metoki H, Asayama K, Obara T, Inoue R, Li Y, Dolan E, Hoshi H, Hashimoto J, Totsune K, Satoh H, Wang JG, O’Brien E, Imai Y. Ambulatory arterial stiffness index and 24-hour ambulatory pulse pressure as predictors of mortality in Ohasama, Japan. Stroke 2007; 38: 1161-1166
  • 15 Leoncini G, Ratto E, Viazzi F, Vaccaro V, Parodi A, Falqui V, Conti N, Tomolillo C, Deferrari G, Pontremoli R. Increased ambulatory arterial stiffness index is associated with target organ damage in primary hypertension. Hypertension 2006; 48: 397-403
  • 16 Ben-Dov IZ, Gavish B, Kark JD, Mekler J, Bursztyn M. A modified ambulatory arterial stiffness index is independently associated with all-cause mortality. J Hum Hypertens 2008; 22: 761-766
  • 17 Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM. The diagnosis of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93: 1526-1540
  • 18 Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M, Christiaens T, Cifko R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F. Task Force Members. 2013; ESH/ESC 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). J Hypertens 2013; 31: 1281-1357
  • 19 Rebellato A, Grillo A, Dassie F, Sonino N, Maffei P, Martini C, Paoletta A, Fabris B, Carretta R, Fallo F. Ambulatory blood pressure monitoring-derived short-term blood pressure variability is increased in Cushing’s syndrome. Endocrine 2014; 47: 557-563
  • 20 Laugesen E, Erlandsen M, Knudsen ST, Hansen KW, Poulsen PL. Ambulatory arterial stiffness index: a composite index reflecting arterial stiffness, blood pressure variability and patients’ diurnal cycle. J Hypertens 2011; 29: 2278-2279
  • 21 Schillaci G, Parati G. Ambulatory arterial stiffness index: merits and limitations of a simple surrogate measure of arterial compliance. J Hypertens 2008; 26: 182-185
  • 22 Gavish B, Izzo JL Jr. Arterial Stiffness: Going a Step Beyond. Am J Hypertens 2016 pii: hpw061 [Epub ahead of print]
  • 23 Aznaouridis K, Vlachopoulos C, Protogerou A, Stefanadis C. Ambulatory systolic-diastolic pressure regression index as a predictor of clinical events: a meta-analysis of longitudinal studies. Stroke 2012; 43: 733-739
  • 24 Laugesen E, Hansen KW, Knudsen ST, Erlandsen M, Ebbehøj E, Poulsen PL. Reproducibility of the ambulatory arterial stiffness index in patients with type 1 diabetes mellitus. Blood Press Monit 2010; 15: 18-22
  • 25 Dechering DG, van der Steen MS, Adiyaman A, Thijs L, Deinum J, Li Y, Dolan E, Akkermans RP, Richart T, Hansen TW, Kikuya M, Wang J, O’Brien E, Thien T, Staessen JA. Reproducibility of the ambulatory arterial stiffness index in hypertensive patients. J Hypertens 2008; 26: 1993-2000
  • 26 Faggiano A, Pivonello R, Spiezia S, De Martino MC, Filippella M, Di Somma C, Lombardi G, Colao A. Cardiovascular risk factors and common carotid artery caliber and stiffness in patients with Cushing’s disease during active disease and 1 year after disease remission. J Clin Endocrinol Metab 2003; 88: 2527-2533
  • 27 Chandran DS, Jaryal AK, Jyotsna VP, Deepak KK. Impaired endothelium mediated vascular reactivity in endogenous Cushing’s syndrome. Endocr J 2011; 58: 789-799
  • 28 Bassareo PP, Marras AR, Pasqualucci D, Mercuro G. Increased arterial rigidity in children affected by Cushing’s syndrome after successful surgical cure. Cardiol Young 2010; 20: 610-614
  • 29 Fallo F, Famoso G, Capizzi D, Sonino N, Dassie F, Maffei P, Martini C, Paoletta A, Iliceto S, Tona F. Coronary microvascular function in patients with Cushing’s syndrome. Endocrine 2013; 43: 206-213
  • 30 McEniery CM. Yasmin Hall IR, Qasem A, Wilkinson IB, Cockcroft JR. Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: the Anglo Cardiff Collaborative Trial (ACCT). J Am Coll Cardiol 2005; 46: 1753-1760
  • 31 Kips JG, Vermeersch SJ, Reymond P, Boutouyrie P, Stergiopulos N, Laurent S, Van Bortel LM, Segers P. Ambulatory arterial stiffness index does not accurately assess arterial stiffness. J Hypertens 2012; 30: 574-580
  • 32 Simon AC, Levenson J, Bouthier J, Safar ME, Avolio AP. Evidence of early degenerative changes in large arteries in human essential hypertension. Hypertension 1985; 7: 675-680
  • 33 Isidori AM, Graziadio C, Paragliola RM, Cozzolino A, Ambrogio AG, Colao A, Corsello SM, Pivonello R. ABC Study Group. The hypertension of Cushing’s syndrome: Controversies in the pathophysiology and focus on cardiovascular complications. J Hypertens 2015; 33: 44-60
  • 34 Avenatti E, Rebellato A, Iannaccone A, Battocchio M, Dassie F, Veglio F, Milan A, Fallo F. Left ventricular geometry and 24-h blood pressure profile in Cushing’s syndrome. Endocrine 2016 [Epub ahead of print] PubMed PMID: 27179657
  • 35 Cuspidi C, Macca G, Sampieri L, Fusi V, Severgnini B, Michev I, Salerno M, Magrini F, Zanchetti A. Target organ damage and non-dipping pattern defined by two sessions of ambulatory blood pressure monitoring in recently diagnosed essential hypertensive patients. J Hypertens 2001; 19: 1539-1545
  • 36 Ohkubo T, Hozawa A, Yamaguchi J, Kikuya M, Ohmori K, Michimata M, Matsubara M, Hashimoto J, Hoshi H, Araki T, Tsuji I, Satoh H, Hisamichi S, Imai Y. Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study. J Hypertens 2002; 20: 2183-2189
  • 37 Verdecchia P, Porcellati C, Schillaci G, Borgioni C, Ciucci A, Battistelli M, Guerrieri M, Matteschi C, Zampi I, Gattucci C, Reboldi G. Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. Hypertension 1994; 24: 793-801
  • 39 Kornel L, Nelson WA, Manisundaram B, Chigurupati R, Hayashi T. Mechanism of the effects of glucocorticoids and mineralocorticoids on vascular smooth muscle contractility. Steroids 1993; 58: 580-587
  • 40 Inoue H, Umesono K, Nishimori T, Hirata Y, Tanabe T. Glucocorticoid-mediated suppression of the promoter activity of the cyclooxygenase-2 gene is modulated by expression of its receptor in vascular endothelial cells. Biochem Biophys Res Commun 1999; 254: 292-298
  • 41 Ong SL, Whitworth JA. How do glucocorticoids cause hypertension: role of nitric oxide deficiency, oxidative stress, and eicosanoids. Endocrinol Metab Clin North Am 2011; 40: 393-407
  • 42 Goodwin JE, Geller DS. Glucocorticoid-induced hypertension. Pediatr Nephrol 2012; 27: 1059-1066
  • 38 Bahrainwala J, Patel A, Diaz KM, Veerabhadrappa P, Cohen DL, Cucchiara A, Townsend RR. Ambulatory Arterial Stiffness Index and circadian blood pressure variability. J Am Soc Hypertens 2015; 9: 705-710
  • 43 Kolade OO, O’Moore-Sullivan TM, Stowasser M, Coombes JS, Fassett RG, Marwick TH, Sharman JE. Arterial stiffness, central blood pressure and body size in health and disease. Int J Obes (Lond) 2012; 6: 93-99
  • 44 Henry RM, Kostense PJ, Spijkerman AM, Dekker JM, Nijpels G, Heine RJ, Kamp O, Westerhof N, Bouter LM, Stehouwer CD. Hoorn Study. Arterial stiffness increases with deteriorating glucose tolerance status: the Hoorn Study. Circulation 2003; 107: 2089-2095
  • 45 Schram MT, Henry RM, van Dijk RA, Kostense PJ, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Westerhof N, Stehouwer CD. Increased central artery stiffness in impaired glucose metabolism and type 2 diabetes: the Hoorn Study. Hypertension 2004; 43: 176-181
  • 46 Doonan RJ, Hausvater A, Scallan C, Mikhailidis DP, Pilote L, Daskalopoulou SS. The effect of smoking on arterial stiffness. Hypertens Res 2010; 33: 398-410