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Ambulatory blood pressure monitoring-derived short-term blood pressure variability is increased in Cushing’s syndrome

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Abstract

Cushing’s syndrome is associated with high cardiovascular morbility and mortality. Blood pressure (BP) variability within a 24-h period is increasingly recognized as an independent predictor of cardiovascular risk. The aim of our study was to investigate the short-term BP variability indices in Cushing’s syndrome. Twenty-five patients with Cushing’s syndrome (mean age 49 ± 13 years, 4 males; 21 Cushing’s disease and 4 adrenal adenoma patients) underwent 24-h ambulatory BP monitoring (ABPM) and evaluation of cardiovascular risk factors. Cushing patients were divided into 8 normotensive (NOR-CUSH) and 17 hypertensive (HYP-CUSH) patients and were compared with 20 normotensive (NOR-CTR) and 20 hypertensive (HYP-CTR) age-, sex-, and BMI-matched control subjects. Short-term BP variability was derived from ABPM and calculated as the following: (1) standard deviation (SD) of 24-h, daytime, and nighttime BP; (2) 24-h weighted SD of BP; and (3) average real variability (ARV), i.e., the average of the absolute differences between consecutive BP measurements over 24 h. In comparison with controls, patients with Cushing’s syndrome, either normotensive or hypertensive, had higher 24-h and daytime SD of BP, as well as higher 24-h weighted SD and ARV of BP (P = 0.03 to P < 0.0001). No difference in metabolic parameters was observed between NOR-CTR and NOR-CUSH or between HYP-CTR and HYP-CUSH subgroups. ABPM-derived short-term BP variability is increased in Cushing’s syndrome, independent of BP elevation. It may represent an additional cardiovascular risk factor in this disease. The role of excess cortisol in BP variability has to be further clarified.

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References

  1. M. Boscaro, L. Barzon, F. Fallo, N. Sonino, Cushing’s syndrome. Lancet 357, 783–791 (2001)

    Article  PubMed  CAS  Google Scholar 

  2. L. Tauchmanovà, R. Rossi, B. Biondi, M. Pulcrano, V. Nuzzo, E.A. Palmieri, S. Fazio, G. Lombardi, Patients with subclinical Cushing’s syndrome due to adrenal adenoma have increased cardiovascular risk. J. Clin. Endocrinol. Metab. 87, 4872–4878 (2002)

    Article  PubMed  Google Scholar 

  3. G. Arnaldi, A. Angeli, A. Atkinson, X. Bertagna, F. Cavagnini, G.P. Chrousos, G.A. Fava, J.W. Findling, R.C. Gaillard, A.B. Grossman, B. Kola, A. Lacroix, T. Mancini, F. Mantero, J. Newell-Price, L.K. Nieman, N. Sonino, M.L. Vance, A. Giustina, M. Boscaro, Diagnosis and complications of Cushing’s syndrome: a consensus statement. J. Clin. Endocrinol. Metab. 88, 5593–5602 (2003)

    Article  PubMed  CAS  Google Scholar 

  4. R. Giordano, F. Guaraldi, R. Berardelli, I. Karamouzis, V. D’Angelo, E. Marinazzo, A. Picu, E. Ghigo, E. Arvat, Glucose metabolism in patients with subclinical Cushing’s syndrome. Endocrine 41, 415–423 (2012)

    Article  PubMed  CAS  Google Scholar 

  5. J.A. Withworth, G.J. Mangos, J.J. Kelly, Cushing, cortisol, and cardiovascular disease. Hypertension 36, 912–916 (2000)

    Article  Google Scholar 

  6. B.R. Walker, Glucocorticoids and cardiovascular disease. Eur. J. Endocrinol. 157, 545–559 (2007)

    Article  PubMed  CAS  Google Scholar 

  7. F. Fallo, N. Sonino, Should we evaluate for cardiovascular disease in patients with Cushing’s syndrome? Clin. Endocrinol. (Oxf.) 71, 768–771 (2009)

    Article  Google Scholar 

  8. F. Fallo, G. Famoso, D. Capizzi, N. Sonino, F. Dassie, P. Maffei, C. Martini, A. Paoletta, S. Iliceto, F. Tona, Coronary microvascular function in patients with Cushing’s syndrome. Endocrine 43, 206–213 (2013)

    Article  PubMed  CAS  Google Scholar 

  9. M.A. Magiakou, P. Smyrnaki, G.P. Chrousos, Hypertension in Cushing’s syndrome. Best Pract. Res. Clin. Endocrinol. Metab. 20, 467–482 (2006)

    Article  PubMed  CAS  Google Scholar 

  10. M.V. Cicala, F. Mantero, Hypertension in Cushing’s syndrome: from pathogenesis to treatment. Neuroendocrinology 92(Suppl 1), 44–49 (2010)

    Article  PubMed  CAS  Google Scholar 

  11. Y. Imai, K. Abe, S. Sasaki, N. Minami, M. Nihei, M. Munakata, O. Murakami, K. Matsue, H. Sekino, Y. Miura, Altered circadian blood pressure rhythm in patients with Cushing’s syndrome. Hypertension 12, 11–19 (1988)

    Article  PubMed  CAS  Google Scholar 

  12. Y. Imai, A. Aihara, T. Ohkubo, K. Nagai, I. Tsuji, N. Minami, H. Satoh, S. Hisamichi, Factors that affect blood pressure variability. A community-based study in Ohasama, Japan. Am. J. Hypertens. 10, 1281–1289 (1997)

    Article  PubMed  CAS  Google Scholar 

  13. C. Cuspidi, G. Macca, L. Sampieri, V. Fusi, B. Severgnini, I. Michev, M. Salerno, F. Magrini, A. Zanchetti, Target organ damage and non-dipping pattern defined by two sessions of ambulatory blood pressure monitoring in recently diagnosed essential hypertensive patients. J. Hypertens. 19, 1539–1545 (2001)

    Article  PubMed  CAS  Google Scholar 

  14. T. Ohkubo, A. Hozawa, J. Yamaguchi, M. Kikuya, K. Ohmori, M. Michimata, M. Matsubara, J. Hashimoto, H. Hoshi, T. Araki, I. Tsuji, H. Satoh, S. Hisamichi, Y. Imai, Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study. J. Hypertens. 20, 2183–2189 (2002)

    Article  PubMed  CAS  Google Scholar 

  15. M. Kikuya, A. Hozawa, T. Ohokubo, I. Tsuji, M. Michimata, M. Matsubara, M. Ota, K. Nagai, T. Araki, H. Satoh, S. Ito, S. Hisamichi, Y. Imai, Prognostic significance of blood pressure and heart rate variabilities: the Ohasama study. Hypertension 36, 901–906 (2000)

    Article  PubMed  CAS  Google Scholar 

  16. L. Mena, S. Pintos, N.V. Queipo, J.A. Aizpúrua, G. Maestre, T. Sulbarán, A reliable index for the prognostic significance of blood pressure variability. J. Hypertens. 23, 505–511 (2005)

    Article  PubMed  CAS  Google Scholar 

  17. G. Bilo, A. Giglio, K. Styczkiewicz, G. Caldara, A. Maronati, K. Kawecka-Jaszcz, G. Mancia, G. Parati, A new method for assessing 24-h blood pressure variability after excluding the contribution of nocturnal blood pressure fall. J. Hypertens. 25, 2058–2066 (2007)

    Article  PubMed  CAS  Google Scholar 

  18. S.D. Pierdomenico, M. Di Nicola, A.L. Esposito, R. Di Mascio, E. Ballone, D. Lapenna, F. Cuccurullo, Prognostic value of different indices of blood pressure variability in hypertensive patients. Am. J. Hypertens. 22, 842–847 (2009)

    Article  PubMed  Google Scholar 

  19. JCS Joint Working Group, Guidelines for the clinical use of 24 h ambulatory blood pressure monitoring (ABPM) (JCS 2010): digest version. Circ. J. 76, 508–519 (2012)

    Article  Google Scholar 

  20. G. Mancia, Short- and long-term blood pressure variability. Present and future. Hypertension 60, 512–517 (2012)

    Article  PubMed  CAS  Google Scholar 

  21. G. Parati, J.E. Ochoa, P. Salvi, C. Lombardi, G. Bilo, Prognostic value of blood pressure variability and average blood pressure levels in patients with hypertension and diabetes. Diabetes Care 36(Suppl 2), S312–S324 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  22. G. Mancia, R. Fagard, K. Narkiewicz, J. Redón, A. Zanchetti, M. Böhm, T. Christiaens, R. Cifkova, G. De Backer, A. Dominiczak, M. Galderisi, D.E. Grobbee, T. Jaarsma, P. Kirchhof, S.E. Kjeldsen, S. Laurent, A.J. Manolis, P.M. Nilsson, L.M. Ruilope, R.E. Schmieder, P.A. Sirnes, P. Sleight, M. Viigimaa, B. Waeber, F. Zannad, 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. 31, 1281–1357 (2013)

    Article  PubMed  CAS  Google Scholar 

  23. P. Della Mea, M. Lupia, V. Bandolin, S. Guzzon, N. Sonino, R. Vettor, F. Fallo, Adiponectin, insulin resistance, and left ventricular structure in dipper and nondipper essential hypertensive patients. Am. J. Hypertens. 18, 30–35 (2005)

    Article  PubMed  Google Scholar 

  24. S.C. Malpas, Neural influences on cardiovascular variability: possibilities and pitfalls. Am. J. Physiol. Heart Circ. Physiol. 282, H6–H20 (2002)

    PubMed  CAS  Google Scholar 

  25. T.N. Thrasher, Baroreceptors and the long-term control of blood pressure. Exp. Physiol. 89, 331–335 (2004)

    Article  PubMed  Google Scholar 

  26. J.A. Whitworth, M.A. Brown, J.J. Kelly, P.M. Williamson, Mechanisms of cortisol-induced hypertension in humans. Steroids 60, 76–80 (1995)

    Article  PubMed  CAS  Google Scholar 

  27. J.A. Whitworth, P.M. Williamson, G. Mangos, J.J. Kelly, Cardiovascular consequences of cortisol excess. Vasc. Health Risk Manag. 1, 291–299 (2005)

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. F. Fallo, P. Maffei, A. Dalla Pozza, M. Carli, P. Della Mea, M. Lupia, F. Rabbia, N. Sonino, Cardiovascular autonomic function in Cushing’s syndrome. J. Endocrinol. Invest. 32, 41–45 (2009)

    Article  PubMed  CAS  Google Scholar 

  29. D.S. Chandran, N. Ali, A.K. Jaryal, V.P. Jyotsna, K.K. Deepak, Decreased autonomic modulation of heart rate and altered cardiac sympathovagal balance in patients with Cushing’s syndrome: role of endogenous hypercortisolism. Neuroendocrinology 97, 309–317 (2013)

    Article  PubMed  CAS  Google Scholar 

  30. A. Faggiano, R. Pivonello, S. Spiezia, M.C. De Martino, M. Filippella, C. Di Somma, G. Lombardi, A. Colao, 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. 88, 2527–2533 (2003)

    Article  PubMed  CAS  Google Scholar 

  31. N. Albiger, R.M. Testa, B. Almoto, M. Ferrari, F. Bilora, F. Petrobelli, A. Pagnan, F. Mantero, C. Scaroni, 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. 38, 405–410 (2006)

    Article  PubMed  CAS  Google Scholar 

  32. M. Baykan, C. Erem, O. Gedikli, A. Hacihasanoglu, T. Erdogan, M. Kocak, I. Durmuş, L. Korkmaz, S. Celik, Impairment of flow-mediated vasodilatation of brachial artery in patients with Cushing’s syndrome. Endocrine 31, 300–304 (2007)

    Article  PubMed  CAS  Google Scholar 

  33. G. Schillaci, G. Bilo, G. Pucci, S. Laurent, I. Macquin-Mavier, P. Boutouyrie, F. Battista, L. Settimi, G. Desamericq, G. Dolbeau, A. Faini, P. Salvi, E. Mannarino, G. Parati, Relationship between short-term blood pressure variability and large-artery stiffness in human hypertension: findings from 2 large databases. Hypertension 60, 369–377 (2012)

    Article  PubMed  CAS  Google Scholar 

  34. R. van der Pas, F.W. Leebeek, L.J. Hofland, W.W. de Herder, R.A. Feelders, Hypercoagulability in Cushing’s syndrome: prevalence, pathogenesis and treatment. Clin. Endocrinol. (Oxf.) 78, 481–488 (2013)

    Article  Google Scholar 

  35. M. Ozawa, K. Tamura, Y. Okano, K. Matsushita, M. Yanagi, Y. Tsurumi-Ikeya, J. Oshikawa, T. Hashimoto, S. Masuda, H. Wakui, A. Shigenaga, K. Azuma, T. Ishigami, Y. Toya, T. Ishikawa, S. Umemura, Identification of an increased short-term blood pressure variability on ambulatory blood pressure monitoring as a coronary risk factor in diabetic hypertensives. Clin. Experim. Hypertens. 31, 259–270 (2009)

    Article  Google Scholar 

  36. N. Sonino, F. Fallo, G.A. Fava, Psychosomatic aspects of Cushing’s syndrome. Rev. Endocr. Metab. Disord. 11, 95–104 (2010)

    Article  PubMed  Google Scholar 

  37. G. van den Berg, M. Frölich, J.D. Veldhuis, F. Roelfsema, Combined amplification of the pulsatile and basal modes of adrenocorticotropin and cortisol secretion in patients with Cushing’s disease: evidence for decreased responsiveness of the adrenal glands. J. Clin. Endocrinol. Metab. 80, 3750–3757 (1995)

    PubMed  Google Scholar 

  38. R.G. Veldman, M. Frölich, S.M. Pincus, J.D. Veldhuis, F. Roelfsema, Apparently complete restoration of normal daily adrenocorticotropin, cortisol, growth hormone, and prolactin secretory dynamics in adults with Cushing’s disease after clinically successful transsphenoidal adenomectomy. J. Clin. Endocrinol. Metab. 85, 4039–4046 (2000)

    PubMed  CAS  Google Scholar 

  39. L. Kornel, W.A. Nelson, B. Manisundaram, R. Chigurupati, T. Hayashi, Mechanism of the effects of glucocorticoids and mineralocorticoids on vascular smooth muscle contractility. Steroids 58, 580–587 (1993)

    Article  PubMed  CAS  Google Scholar 

  40. H. Inoue, K. Umesono, T. Nishimori, Y. Hirata, T. Tanabe, 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. 254, 292–298 (1999)

    Article  PubMed  CAS  Google Scholar 

  41. S.L. Ong, J.A. Whitworth, How do glucocorticoids cause hypertension: role of nitric oxide deficiency, oxidative stress, and eicosanoids. Endocrinol. Metab. Clin. N. Am. 40, 393–407 (2011)

    Article  CAS  Google Scholar 

  42. J.E. Goodwin, D.S. Geller, Glucocorticoid-induced hypertension. Pediatr. Nephrol. 27, 1059–1066 (2012)

    Article  PubMed  Google Scholar 

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Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. This research did not receive any specific grant from any funding agency in the public commercial or non-profit section.

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Authors and Affiliations

  1. Department of Medicine-DIMED, Clinica Medica 3, University of Padova, Via Giustiniani 2, 35128, Padua, Italy

    Andrea Rebellato, Francesca Dassie, Pietro Maffei, Chiara Martini & Francesco Fallo

  2. Department of Medical, Surgical and Healthy Science, University of Trieste, Trieste, Italy

    Andrea Grillo, Bruno Fabris & Renzo Carretta

  3. Department of Statistical Sciences, University of Padova, Padua, Italy

    Nicoletta Sonino

  4. Endocrinology Outpatient Service, Cittadella Hospital, Cittadella, Italy

    Agostino Paoletta

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  1. Andrea Rebellato
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  2. Andrea Grillo
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Correspondence to Francesco Fallo.

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Andrea Rebellato and Andrea Grillo have contributed equally to this work.

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Rebellato, A., Grillo, A., Dassie, F. et al. Ambulatory blood pressure monitoring-derived short-term blood pressure variability is increased in Cushing’s syndrome. Endocrine 47, 557–563 (2014). https://doi.org/10.1007/s12020-014-0164-7

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  • DOI: https://doi.org/10.1007/s12020-014-0164-7

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