A study of radiation-induced carotid atherosclerosis in patients treated with radiotherapy for nasopharyngeal carcinoma

Abstract

Carotid atherosclerosis is a common complication in patients treated with radiotherapy (RT) for nasopharyngeal carcinoma (NPC). Since patients with carotid atherosclerosis have a higher risk of cerebrovascular events, assessment of carotid atherosclerosis is crucial for post-RT NPC patients so that early diagnosis and timely management can be given to them. The present study evaluated the reliability of ultrasonography in measuring carotid artery wall thickness and stiffness, and investigated the severity, predictor and genetic involvement of radiation-induced carotid atherosclerosis in post-RT NPC patients. Thirty subjects were recruited to evaluate the inter- and intra-observer reliability of Radiofrequency-based Quality Intima-Media Thickness (RF-QIMT) in assessing carotid IMT (CIMT) and Radiofrequency-based Quality Arterial Stiffness (RF-QAS) in measuring carotid arterial stiffness (CAS). Results showed that RF-QIMT and RF-QAS had excellent inter- and intra-observer reliability in assessing CIMT and CAS respectively (Intraclass correlation coefficient >0.75, P<0.001). To compare the ultrasound features of radiation-induced and spontaneous carotid atherosclerosis, 69 post-RT NPC patients and 70 type 2 diabetics were recruited. Another 76 healthy subjects were also included as the controls. For each participant, carotid atherosclerotic parameters, including CIMT, CAS, carotid plaque score, and the presence of plaque and ≥50% carotid stenosis, were assessed using ultrasonography. Post-RT NPC patients and type 2 diabetics had significantly higher CIMT, CAS and carotid plaque burden as compared to healthy subjects (Corrected P value, Pcor<0.05). In addition, when compared with the spontaneous carotid atherosclerosis in type 2 diabetics, the radiation-induced carotid atherosclerosis in post-RT NPC patients was more severe with higher CAS and carotid plaque burden (Pcor<0.05). To investigate the predictors of the extent of radiation-induced carotid atherosclerosis, 129 post-RT NPC patients were included. Ultrasonography was used for assessing the carotid atherosclerotic parameters. The association between carotid atherosclerosis and ten potential predictors was assessed using multiple regressions. Results showed that age, post-RT duration and number of cardiovascular risk factors were significantly associated with the extent of radiation-induced carotid atherosclerosis (Pcor<0.05). The age of 44.5 years and the post-RT duration of 8.5 years were the cutoff values for detecting carotid plaque, whilst the post-RT duration of 13.5 years and 1.5 conventional cardiovascular risk factors were the cutoff values for predicting ≥50% stenosis (Pcor<0.05). In the association analyses between genetic polymorphisms and radiation-induced carotid atherosclerosis, 128 post-RT NPC patients were involved. Thirteen single nucleotide polymorphisms were genotyped. Carotid atherosclerotic parameters were assessed using ultrasonography. Results demonstrated that TC haplotype in rs662-rs705379 of PON1 was significantly associated with higher carotid plaque score (Pcor<0.05). In conclusion, RF-QIMT and RF-QAS are reliable ultrasound techniques in assessing CIMT and CAS respectively. Radiation-induced carotid atherosclerosis is more severe than spontaneous carotid atherosclerosis. Age, post-RT duration and number of cardiovascular risk factors are significant predictors of the extent of radiation-induced carotid atherosclerosis. Post-RT NPC patients, who are aged 45 years or older, with post-RT duration of 9 years or above, having ≥2 cardiovascular risk factors, and/or carrying TC haplotype in rs662-rs705379, tend to have a higher degree of carotid atherosclerosis and may need more concerns for early diagnosis of carotid atherosclerosis.