Ultraschall Med 2017; 38(02): 190-197
DOI: 10.1055/s-0034-1399293
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Ultrasound Evaluation of Carotid Atherosclerosis in Post-Radiotherapy Nasopharyngeal Carcinoma Patients, Type 2 Diabetics, and Healthy Controls

Sonografische Bewertung der Arteriosklerose der Carotis bei Patienten mit Nasopharynxkarzinom nach Bestrahlung, Typ-2-Diabetikern und gesunden Kontrollprobanden
Chuang Yuan
1   Medical Research Center, Changsha Central Hospital, Changsha, China
,
Vincent WC Wu
2   Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong
,
Shea Ping YIP
2   Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong
,
Dora LW Kwong
3   Department of Clinical Oncology, The University of Hong Kong
,
Michael Ying
2   Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong
› Author Affiliations
Further Information

Publication History

04 November 2014

06 February 2015

Publication Date:
01 April 2015 (online)

Abstract

Purpose To comprehensively evaluate and compare the degree of carotid atherosclerosis in patients treated with radiotherapy (RT) for nasopharyngeal carcinoma (NPC) and in patients with type 2 diabetes mellitus (DM), and using healthy subjects as controls.

Materials and Methods The present study recruited 69 post-RT NPC patients without conventional cardiovascular risk factors, 70 type 2 diabetic patients without previous RT, and 76 healthy controls without conventional cardiovascular risk factors and previous RT. For each participant, 5 carotid atherosclerotic parameters, namely carotid intima-media thickness (CIMT), carotid arterial stiffness (CAS), presence of carotid plaque, carotid plaque score, and presence of ≥ 50 % carotid stenosis, were assessed using ultrasonography. The differences in these carotid atherosclerotic parameters between study groups were compared using ANCOVA or logistic regression after the adjustment for age and gender. Multiple comparisons were corrected using the Benjamini-Hochberg false discovery rate.

Results Post-RT NPC patients and type 2 diabetics had a significantly higher CIMT, CAS and carotid plaque burden compared to the healthy subjects (corrected P-value, Pcor < 0.05). In addition, carotid atherosclerosis in post-RT NPC patients tended to be more severe with significantly higher CAS and carotid plaque burden than that in type 2 diabetics (Pcor < 0.05).

Conclusion Neck RT for NPC is an independent risk factor of carotid atherosclerosis, and radiation induces more severe carotid atherosclerosis in post-RT NPC patients. Thus, assessment of carotid atherosclerosis using ultrasonography may be necessary for these patients and should be indicated in the routine follow-up of NPC.

Zusammenfassung

Ziel Umfassende Bewertung und Vergleich des Arteriosklerosegrades der Karotis bei Patienten mit Nasopharynxkarzinom (NPC), bei denen eine Radiotherapie (RT) durchgeführt wurde, bei Patienten mit Diabetes-Typ-2 (DM) sowie bei gesunden Kontrollprobanden.

Material und Methoden Diese aktuelle Studie rekrutierte 69 post-RT NPC-Patienten, die keine üblichen kardiovaskulären Risikofaktoren hatten, 70 Patienten mit Diabetes Typ-2 ohne vorherige RT und 76 gesunden Kontrollprobanden ohne kardiovaskuläre Risikofaktoren und ohne vorherige RT. Für jeden Teilnehmer wurden sonografisch 5 Parameter einer Karotis-Arteriosklerose ermittelt, die Karotis-Intima-Media-Dicke (CIMT), die Steifigkeit der Karotisarterie (CAS), das Vorhandensein einer Karotisplaque, der Karotisplaque-Grad und das Auftreten einer ≥ 50 % Karotisstenose. Unterschiede dieser Karotis-Arteriosklerose-Parameter zwischen den Studiengruppen wurden mittels ANCOVA oder logistischer Regression nach Anpassung von Alter und Geschlecht verglichen. Multiple Vergleiche wurden mit der „False Discovery Rate“ (Benjamini-Hochberg-Prozedur) korrigiert.

Ergebnisse Die Patienten mit NPC nach RT und mit Diabetes-Typ-2 hatten signifikant höhere CIMT-, CAS- und Karotisplaque-Lasten im Vergleich zu gesunden Probanden (korrigierter P-Wert, Pcor < 0,05). Darüber hinaus schien die Karotisstenose von NPC-Patienten nach RT noch schwerer zu verlaufen mit signifikant höheren CAS und Karotisplaque-Lasten als in Typ-2-Diabetikern (Pcor < 0,05).

Schlussfolgerung Die Radiotherapie am Hals ist bei NPC ein unabhängiger Risikofaktor für eine Arteriosklerose der A. carotis, sie induziert eine hochgradige Karotis-Arteriosklerose. Daher sollte die sonografische Untersuchung auf eine Karotisstenose bei Patienten mit NPC Bestandteil der Routine-Nachsorge sein.

 
  • References

  • 1 Chang ET. Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiology Biomarkers & Prevention 2006; 15: 1765-1777
  • 2 Glastonbury CM. Nasopharyngeal carcinoma: the role of magnetic resonance imaging in diagnosis, staging, treatment, and follow-up. Topics in magnetic resonance imaging: TMRI 2007; 18: 225-235
  • 3 Lu H. Yao M. The current status of intensity-modulated radiation therapy in the treatment of nasopharyngeal carcinoma. Cancer Treat Rev 2008; 34: 27-36
  • 4 Muzaffar K. Collins SL. Labropoulos N. et al. A prospective study of the effects of irradiation on the carotid artery. The Laryngoscope 2000; 110: 1811-1814
  • 5 Lam WW. Leung SF. So NM. et al. Incidence of carotid stenosis in nasopharyngeal carcinoma patients after radiotherapy. Cancer 2001; 92: 2357-2363
  • 6 Lam WW. Yuen HY. Wong KS. et al. Clinically underdetected asymptomatic and symptomatic carotid stenosis as a late complication of radiotherapy in Chinese nasopharyngeal carcinoma patients. Head Neck 2001; 23: 780-784
  • 7 Li CS. Schminke U. Tan TY. Extracranial carotid artery disease in nasopharyngeal carcinoma patients with post-irradiation ischemic stroke. Clinical neurology and neurosurgery 2010; 112: 682-686
  • 8 Chu CN. Chen PC. Bai LY. et al. Young nasopharyngeal cancer patients with radiotherapy and chemotherapy are most prone to ischaemic risk of stroke: a national database, controlled cohort study. Clinical otolaryngology: official journal of ENT-UK official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery 2013; 38: 39-47
  • 9 Beckman JA. Creager MA. Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA 2002; 287: 2570-2581
  • 10 Yuan C. Lai CW. Chan LW. et al. Cumulative effects of hypertension, dyslipidemia, and chronic kidney disease on carotid atherosclerosis in Chinese patients with type 2 diabetes mellitus. Journal of diabetes research 2014; 2014 DOI: 179686.
  • 11 Leborgne L. Pakala R. Dilcher C. et al. Effect of antioxidants on atherosclerotic plaque formation in balloon-denuded and irradiated hypercholesterolemic rabbits. Journal of cardiovascular pharmacology 2005; 46: 540-547
  • 12 Leborgne L. Fournadjiev J. Pakala R. et al. Antioxidants attenuate atherosclerotic plaque development in a balloon-denuded and irradiated hypercholesterolemic rabbit. Cardiovascular radiation medicine 2003; 4: 25-28
  • 13 Hoving S. Heeneman S. Gijbels MJ. et al. NO-donating aspirin and aspirin partially inhibit age-related atherosclerosis but not radiation-induced atherosclerosis in ApoE null mice. PloS one 2010; 5: e12874
  • 14 Alberti KG. Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998; 15: 539-553
  • 15 Carretero OA. Oparil S. Essential hypertension Part I: Definition and etiology. Circulation 2000; 101: 329-335
  • 16 Ford ES. Li CY. Pearson WS. et al. Trends in hypercholesterolemia, treatment and control among United States adults. International Journal of Cardiology 2010; 140: 226-235
  • 17 Chang YJ. Chang TC. Lee TH. et al. Predictors of carotid artery stenosis after radiotherapy for head and neck cancers. J Vasc Surg 2009; 50: 280-285
  • 18 Matthews KA. Kuller LH. Sutton-Tyrrell K. et al. Changes in cardiovascular risk factors during the perimenopause and postmenopause and carotid artery atherosclerosis in healthy women. Stroke 2001; 32: 1104-1111
  • 19 Benjamini Y. Hochberg Y. Controlling the False Discovery Rate – a Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society Series B-Methodological 1995; 57: 289-300
  • 20 Wagenknecht LE. Zaccaro D. Espeland MA. et al. Diabetes and progression of carotid atherosclerosis – The Insulin Resistance Atherosclerosis Study. Arteriosclerosis Thrombosis and Vascular Biology 2003; 23: 1035-1041
  • 21 Giannarelli C. Bianchini E. Bruno RM. et al. Local carotid stiffness and intima-media thickness assessment by a novel ultrasound-based system in essential hypertension. Atherosclerosis 2012; 223: 372-377
  • 22 De Angelis M. Scrucca L. Leandri M. et al. Prevalence of carotid stenosis in Type 2 diabetic patients asymptomatic for cerebrovascular disease. Diabetes Nutrition & Metabolism 2003; 16: 48-55
  • 23 Zidar N. Ferluga D. Hvala A. et al. Contribution to the pathogenesis of radiation-induced injury to large arteries. Journal of Laryngology and Otology 1997; 111: 988-990
  • 24 Hallahan D. Kuchibhotla J. Wyble C. Cell adhesion molecules mediate radiation-induced leukocyte adhesion to the vascular endothelium. Cancer research 1996; 56: 5150-5155
  • 25 Heckmann M. Douwes K. Peter R. et al. Vascular activation of adhesion molecule mRNA and cell surface expression by ionizing radiation. Experimental cell research 1998; 238: 148-154
  • 26 Stewart FA. Hoving S. Russell NS. Vascular Damage as an Underlying Mechanism of Cardiac and Cerebral Toxicity in Irradiated Cancer Patients. Radiation Research 2010; 174: 865-869
  • 27 Chi Z. Melendez AJ. Role of cell adhesion molecules and immune-cell migration in the initiation, onset and development of atherosclerosis. Cell Adh Migr 2007; 1: 171-175
  • 28 Milliat F. Francois A. Isoir M. et al. Influence of endothelial cells on vascular smooth muscle cells phenotype after irradiation – Implication in radiation-induced vascular damages. American Journal of Pathology 2006; 169: 1484-1495
  • 29 Riley PA. Free radicals in biology: oxidative stress and the effects of ionizing radiation. Int J Radiat Biol 1994; 65: 27-33
  • 30 Tribble DL. Barcellos-Hoff MH. Chu BM. et al. Ionizing radiation accelerates aortic lesion formation in fat-fed mice via SOD-inhibitable processes. Arterioscler Thromb Vasc Biol 1999; 19: 1387-1392
  • 31 Park JG. Oh GT. The role of peroxidases in the pathogenesis of atherosclerosis. BMB reports 2011; 44: 497-505
  • 32 Plummer C. Henderson RD. O'Sullivan JD. et al. Ischemic Stroke and Transient Ischemic Attack After Head and Neck Radiotherapy A Review. Stroke ; a journal of cerebral circulation 2011; 42: 2410-2418
  • 33 Huang TL. Hsu HC. Chen HC. et al. Long-term effects on carotid intima-media thickness after radiotherapy in patients with nasopharyngeal carcinoma. Radiat Oncol 2013; 8: 261
  • 34 Tegos TJ. Stavropoulos P. Sabetai MM. et al. Determinants of carotid plaque instability: Echoicity versus heterogeneity. Eur J Vasc Endovasc 2001; 22: 22-30
  • 35 Kanber B. Hartshorne TC. Horsfield MA. et al. Dynamic variations in the ultrasound greyscale median of carotid artery plaques. Cardiovascular ultrasound 2013; 11: 21
  • 36 Kanber B. Hartshorne TC. Horsfield MA. et al. Quantitative assessment of carotid plaque surface irregularities and correlation to cerebrovascular symptoms. Cardiovascular ultrasound 2013; 11: 38