Original Article Arterial Stiffness as a Biomarker of Radiation-Induced Carotid Atherosclerosis Dorothy M. Gujral, PhD 1 , Benoy N. Shah, MBBS 2 , Navtej S. Chahal, PhD 2 , Sanjeev Bhattacharyya, MD 2 , Roxy Senior, MD 2 , Kevin J. Harrington, PhD 1 , and Christopher M. Nutting, PhD 1 Abstract Arterial stiffness is thought to be a precursor to atherosclerosis. Conventional arterial stiffness parameters as potential biomarkers of radiation-induced damage were investigated. Patients with head and neck cancer treated with radiotherapy 2 years previously to one side of the neck were included. The unirradiated side was the internal control. Beta stiffness index (B) and elastic modulus (Ep) were used to assess arterial stiffness and were measured in proximal, mid, and distal common carotid artery (CCA) and compared with the corresponding unirradiated segments. Fifty patients (68% male; median age 58 years; interquartile range 50-62) were included. Mean + standard deviation maximum doses to irradiated and unirradiated arteries were 53 + 13 and 1.9 + 3.7 Gy, respectively. Differences in B were not significant. Significant differences in Ep were demon- strated—proximal CCA: 1301 + 1223 versus 801 + 492 (P < .0001), mid CCA: 1064 + 818 versus 935.5 + 793 (P < .0001), and distal CCA: 1267 + 1084 versus 775.3 + 551.9 (P < .0001). Surgery had no impact on arterial stiffness. Arterial stiffness is increased in irradiated arteries, in keeping with radiation-induced damage. Prospective data may show an association between arterial stiffness and atherosclerosis in this setting. Keywords arterial stiffness, carotid, radiotherapy, atherosclerosis Introduction Vascular injury is a prominent feature of radiation-induced normal tissue damage. 1-3 Studies in patients with rectal 4 and lung cancers 5 have demonstrated changes in large vessels including vessel edema, perivascular, and intravascular fibrosis in surgical specimens weeks after radiation. Studies in rodent models have demonstrated very early changes in microvascular function, noting an inflammatory response with leukocyte infil- tration into perivascular tissues within hours of radiation expo- sure. 6,7 Fibrin deposition in the extravascular space was noted with increased vascular permeability. It is not clear whether these early changes are precursors of chronic fibrosis, and recent translational work is starting to characterize chronic vas- cular injury. 8-10 Increased fibrin deposition and consequent fibrosis may result in changes to the structure of the arterial wall with altered compliance and distensibility of the vessel. Arterial stiffness is thought to be a biomarker of subclinical atherosclerosis and is associated with cardiovascular events. 11 It is also possible that radiation-induced fibrosis may result in increased arterial stiffness and, consequently, may be a potential biomarker of radiation-induced atherosclerosis. This process would therefore have implications for patients treated with radiotherapy (RT) for head and neck cancer, breast cancer, and lymphomas, where the carotid arteries are included in the radiation field. Arterial stiffness may be a useful biomarker in this setting. 12 There are several surrogate markers for arterial stiffness based either on pulse pressure or on distending pressure along with arterial diameter measurements to estimate vascular stiff- ness. There is currently no gold standard for evaluating arterial stiffness and, as a result, a number of different methods, includ- ing distensibility, compliance, elastic modulus (Ep), and beta stiffness index (B), are used to assess local arterial stiff- ness. 13-15 The obvious problem with these methods is the fact that arteries are not homogeneous tubes, and mechanical prop- erties can vary in different parts of the artery. Therefore, to allow for this, measurements should be taken at different sec- tions of the artery. In this study, we investigated whether there were differences in 2 standard measures of arterial stiffness between irradiated 1 Head and Neck Unit, The Royal Marsden Hospital, London, United Kingdom 2 Department of Echocardiography, Royal Brompton Hospital, London, United Kingdom Corresponding Author: Christopher M. Nutting, Head and Neck Unit, Royal Marsden Hospital, 203 Fulham Rd, London, SW3 6JJ, United Kingdom. Email: Chris.Nutting@rmh.nhs.uk Angiology 1-6 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319715589520 ang.sagepub.com