Download PDF
Horm Metab Res 2025; 57(04): 229-235
DOI: 10.1055/a-2541-9821
Original Article: Endocrine Care

The Coronary Artery Calcium Score as Prognostic Tool for Cardiovascular Events in Patients with Cushing’s Syndrome

Lukas van Baal
1   Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany (Ringgold ID: RIN39081)
,
Nils Lehmann
2   Institute for Medical Informatics, Biometrics and Epidemiology, University Hospital Essen, Essen, Germany (Ringgold ID: RIN39081)
,
Karl-Heinz Jöckel
2   Institute for Medical Informatics, Biometrics and Epidemiology, University Hospital Essen, Essen, Germany (Ringgold ID: RIN39081)
,
Raimund Erbel
2   Institute for Medical Informatics, Biometrics and Epidemiology, University Hospital Essen, Essen, Germany (Ringgold ID: RIN39081)
,
Lale Umutlu
3   Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany (Ringgold ID: RIN39081)
,
Thomas Schlosser
3   Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany (Ringgold ID: RIN39081)
,
Dagmar Führer
1   Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany (Ringgold ID: RIN39081)
,
Nicole Unger
1   Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany (Ringgold ID: RIN39081)
› Author AffiliationsThe HNR study is funded by a contract with the private Heinz Nixdorf Foundation, Essen, Germany and undergoes continuous monitoring by governmental agencies (DLR) lead by the German Ministry of Education and Science (BMBF) and German Research Council (ER-155/6-2). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
LvB is supported by the DFG funded Clinician Scientist Programme UMEA (FU 356/12-1).
› Further Information
Also available at
    Permissions and Reprints

Abstract

Cushing’s syndrome (CS) is associated with high morbidity and mortality triggered by increased risk for cardiovascular events. Nevertheless, no screening tool to predict the individual risk for these events in patients with Cushing’s syndrome has been established. Nonenhanced electron-beam computed tomography scans with calculation of the Coronary Artery Calcium (CAC) score may offer a non-invasive method. Hence, we evaluated the diagnostic accuracy of Agatston score to predict the risk of a cardiac event in patients with Cushing’s syndrome. Single center prospective study of 34 patients with endogenous CS Multidetector computer tomography and calculation of CAC score was performed at diagnosis of CS. Prevalence of cardiovascular events was documented with median follow-up over 5 years and results were compared with data from the Heinz Nixdorf Recall (HNR) Study. In addition, correlations of CAC score with parameters of cortisol excess were evaluated. CAC score was significantly higher in CS patients with a cardiovascular event than in patients without an event (117 vs. 90; p=<0.01). An odds ratio of 31.7 (p=0.03, 95% CI: 1.3–773.0) for a cardiovascular event could be shown in Cushing’s syndrome patients with a CAC score>75th risk factor-specific reference percentile, while the odds ratio in the HNR study was 4.5 (p<0.01, 95% CI: 3.0–6.9). No correlation between the degree of cortisol excess and CAC score was evident. The CAC score>75th risk factor-specific reference percentile could offer a useful screening tool to precise the cardiovascular risk in patients with Cushing’s syndrome.

Keywords

adrenal - hypercortisolism - coronary artery calcium - coronary artery disease - electron-beam computed tomography

Supplementary Material



Publication History

Received: 05 September 2024

Accepted after revision: 16 February 2025

Article published online:
17 March 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Arnaldi G, Angeli A, Atkinson AB. et al. Diagnosis and complications of Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab 2003; 88: 5593-5602
    CrossrefPubMedSearch in Google Scholar
  • 2 Fallo F, Sonino N. Should we evaluate for cardiovascular disease in patients with Cushing’s syndrome?. Clin Endocrinol (Oxf) 2009; 71: 768-771
    CrossrefPubMedSearch in Google Scholar
  • 3 Virmani R, Kolodgie FD, Burke AP. et al. Lessons from sudden coronary death. Arterioscler Thromb Vasc Biol 2000; 20: 1262-1275
    CrossrefPubMedSearch in Google Scholar
  • 4 Schmermund A, Möhlenkamp S, Berenbein S. et al. Population-based assessment of subclinical coronary atherosclerosis using electron-beam computed tomography. Atherosclerosis 2006; 185: 177-182
    CrossrefPubMedSearch in Google Scholar
  • 5 Brown ER, Kronmal RA, Bluemke DA. et al. Coronary calcium coverage score: determination, correlates, and predictive accuracy in the Multi-Ethnic Study of Atherosclerosis. Radiology 2008; 247: 669-675
    CrossrefPubMedSearch in Google Scholar
  • 6 Agatston AS, Janowitz WR, Hildner FJ. et al. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990; 15: 827-832
    CrossrefPubMedSearch in Google Scholar
  • 7 Erbel R, Möhlenkamp S, Lehmann N. et al. Sex related cardiovascular risk stratification based on quantification of atherosclerosis and inflammation. Atherosclerosis 2008; 197: 662-672
    CrossrefPubMedSearch in Google Scholar
  • 8 Budoff MJ, Nasir K, McClelland RL. et al. Coronary calcium predicts events better with absolute calcium scores than age-sex-race/ethnicity percentiles: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol 2009; 53: 345-352
    CrossrefPubMedSearch in Google Scholar
  • 9 Wahl S, Möhlenkamp S, Erbel R. et al. Screening results for subclinical coronary artery calcification in asymptomatic individuals in relation to a detailed parental history of premature coronary heart disease. Eur J Epidemiol 2013; 28: 301-310
    CrossrefPubMedSearch in Google Scholar
  • 10 Erbel R, Delaney JA, Lehmann N. et al. Signs of subclinical coronary atherosclerosis in relation to risk factor distribution in the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR). Eur Heart J 2008; 29: 2782-2791
    CrossrefPubMedSearch in Google Scholar
  • 11 Mach F, Baigent C, Catapano AL. et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41: 111-188
    CrossrefPubMedSearch in Google Scholar
  • 12 Thilo C, Standl E, Knez A. et al. Coronary calcification in long-term type 1 diabetic patients -- a study with multi slice spiral computed tomography. Exp Clin Endocrinol Diabetes 2004; 112: 561-565
    Thieme ConnectPubMedSearch in Google Scholar
  • 13 Herrmann BL, Severing M, Schmermund A. et al. Impact of disease duration on coronary calcification in patients with acromegaly. Exp Clin Endocrinol Diabetes 2009; 117: 417-422
    Thieme ConnectPubMedSearch in Google Scholar
  • 14 Schmermund A, Möhlenkamp S, Stang A. et al. Assessment of clinically silent atherosclerotic disease and established and novel risk factors for predicting myocardial infarction and cardiac death in healthy middle-aged subjects: rationale and design of the Heinz Nixdorf RECALL Study. Risk factors, evaluation of coronary calcium and lifestyle. Am Heart J 2002; 144: 212-218
    CrossrefPubMedSearch in Google Scholar
  • 15 van Baal L, Lehmann N, Joeckel K-H. et al. Supplementary: the coronary artery calcium score as prognostic tool for cardiovascular events in patients with Cushing’s syndrome. In figshare. 2024 https://doi.org/10.6084/m9.figshare.25965199.v1
    CrossrefPubMedSearch in Google Scholar
  • 16 Nieman LK, Biller BMK, Findling JW. et al. The diagnosis of Cushing's syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93: 1526-1540
    CrossrefPubMedSearch in Google Scholar
  • 17 Erbel R, Eisele L, Moebus S. et al. [The Heinz Nixdorf Recall study]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2012; 55: 809-815
    CrossrefPubMedSearch in Google Scholar
  • 18 Erbel R, Lehmann N, Churzidse S. et al. Progression of coronary artery calcification seems to be inevitable, but predictable – results of the Heinz Nixdorf Recall (HNR) study. Eur Heart J 2014; 35: 2960-2971
    CrossrefPubMedSearch in Google Scholar
  • 19 Carrabba N, Schuijf JD, de Graaf FR. et al. Diagnostic accuracy of 64-slice computed tomography coronary angiography for the detection of in-stent restenosis: a meta-analysis. J Nucl Cardiol 2010; 17: 470-478
    CrossrefPubMedSearch in Google Scholar
  • 20 Neary NM, Booker OJ, Abel BS. et al. Hypercortisolism is associated with increased coronary arterial atherosclerosis: analysis of noninvasive coronary angiography using multidetector computerized tomography. J Clin Endocrinol Metab 2013; 98: 2045-2052
    CrossrefPubMedSearch in Google Scholar
  • 21 Barahona MJ, Resmini E, Viladés D. et al. Coronary artery disease detected by multislice computed tomography in patients after long-term cure of Cushing's syndrome. J Clin Endocrinol Metab 2013; 98: 1093-1099
    CrossrefPubMedSearch in Google Scholar
  • 22 Fallo F, Famoso G, Capizzi D. et al. Coronary microvascular function in patients with Cushing's syndrome. Endocrine 2013; 43: 206-213
    CrossrefPubMedSearch in Google Scholar
  • 23 Erem C, Nuhoglu I, Yilmaz M. et al. Blood coagulation and fibrinolysis in patients with Cushing's syndrome: increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels. J Endocrinol Invest 2009; 32: 169-174
    CrossrefPubMedSearch in Google Scholar
  • 24 Zacharieva S, Atanassova I, Orbetzova M. et al. Vascular endothelial growth factor (VEGF), prostaglandin E2(PGE2) and active renin in hypertension of adrenal origin. J Endocrinol Invest 2004; 27: 742-746
    CrossrefPubMedSearch in Google Scholar
  • 25 Stewart PM, Walker BR, Holder G. et al. 11 beta-Hydroxysteroid dehydrogenase activity in Cushing's syndrome: explaining the mineralocorticoid excess state of the ectopic adrenocorticotropin syndrome. J Clin Endocrinol Metab 1995; 80: 3617-3620
    PubMedSearch in Google Scholar
  • 26 Deuchar GA, McLean D, Hadoke PWF. et al. 11b-hydroxysteroid dehydrogenase type 2 deficiency accelerates atherogenesis and causes proinflammatory changes in the endothelium in apoe-/- mice. Endocrinology 2011; 152: 236-246
    CrossrefPubMedSearch in Google Scholar
  • 27 Bild DE, Detrano R, Peterson D. et al. Ethnic differences in coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation 2005; 111: 1313-1320
    CrossrefPubMedSearch in Google Scholar