Increased Carotid Intima-Media Thickness and Reduced Distensibility in Human Class III Obesity: Independent and Differential Influences of Adiposity and Blood Pressure on the Vasculature

et al. (2013) Increased Carotid Intima-Media Thickness and Reduced Distensibility in Human Class III Obesity: Independent and Differential Influences of Adiposity and Blood Pressure on the Vasculature. PLoS ONE 8(1): e53972. doi:10.1371/journal.pone.0053972 Increased Carotid Intima-Media Thickness and Reduced Distensibility in Human Class III Obesity: Independent and Differential Influences of Adiposity and Blood Pressure on the Vasculature Xiao L. Moore 0 Danielle Michell 0 Sabrina Lee 0 Michael R. Skilton 0 Rajesh Nair 0 John B. Dixon 0 Anthony M. Dart 0 Jaye Chin-Dusting 0 0 1 Baker IDI Heart and Diabetes Institute , Melbourne, Victoria , Australia , 2 The Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, The University of Sydney , Camperdown, New South Wales , Australia , 3 Obesity Research Unit, Department of General Practise, Monash University , Clayton, Victoria , Australia , 4 Alfred Heart Centre, Alfred Hospital , Prahran, Victoria , Australia Carotid intima-media-thickness (cIMT) and carotid distensibility (distensibility), structural and functional properties of carotid arteries respectively, are early markers, as well as strong predictors of cardiovascular disease (CVD). The characteristic of these two parameters in individuals with BMI.40.0 kg/m2 (Class III obesity), however, are largely unknown. The present study was designed to document cIMT and distensibility in this population and to relate these to other factors with established association with CVD in obesity. The study included 96 subjects (65 with BMI.40.0 kg/m2 and 31, age- and 2 gender-matched, with BMI of 18.5 to 30.0 kg/m ). cIMT and distensibility were measured by non-invasive high resolution ultrasonography, circulatory CD133+/KDR+ angiogenic cells and endothelial microparticles (EMP) by flow cytometry, and plasma levels of adipokines, growth factors and cytokines by Luminex immunoassay kits. The study results demonstrated increased cIMT (0.6260.11 mm vs. 0.5460.08 mm, P = 0.0002) and reduced distensibility (22.52610.79 1023kpa21 vs. 29.91612.37 1023kpa21, P,0.05) in individuals with BMI.40.0 kg/m2. Both cIMT and distensibility were significantly associated with traditional CVD risk factors, adiposity/adipokines and inflammatory markers but had no association with circulating angiogenic cells. We also demonstrated, for the first time, elevated plasma EMP levels in individuals with BMI.40.0 kg/m2. In conclusion, cIMT is increased and distensibility reduced in Class III obesity with the changes predominantly related to conventional CVD risk factors present in this condition, demonstrating that both cIMT and distensibility remain as CVD markers in Class III obesity. Editor; Guillermo Lo pez-Lluch; Universidad Pablo de Olavide; Centro Andaluz de Biologa del Desarrollo-CSIC; Spain - Carotid intima-media-thickness (cIMT) and carotid distensibility (distensibility) represent structural and functional properties of carotid arteries respectively. Both increased cIMT, a noninvasive measure of subclinical atherosclerosis, and reduced distensibility, an indicator of regional artery stiffness, are independent predictors of future cardiovascular events [1,2]. Importantly, a combined assessment of the two allows for a better analysis of the individual atherosclerotic burden and improved prediction of aortic atherosclerosis [3]. Increased cIMT or decreased distensibility has been linked to hypertension [4], diabetes mellitus [5] and obesity [610], determinant risk factors for cardiovascular disease (CVD) [11 14]. The occurrence of these three co-morbidities is linked with chronic low-grade inflammation. Furthermore insulin resistance present in obesity is believed to be a principal contributor to this link. The inter-relation between adipogenesis, inflammation, insulin resistance, hypertension and diabetes mellitus remains a current focus of obesity research. Nevertheless higher CVD incidences are evident in hypertensive and/or diabetic obese compared to non-obese counterparts. The prevalence of obesity is rising at an alarming rate worldwide. Moreover the prevalence of Class III obesity, defined as BMI$40.0 kg/m2, is increasing at an even steeper rate [15,16]. cIMT and distensibility in Class III obesity, however, are largely undocumented with only two papers providing both cIMT and distensibility data in people with BMI$40.0 kg/m2 [17,18]. Similarly, little information is available in Class III obesity on novel biomarkers of CVD, such as circulatory angiogenic cells [19] or endothelial microparticles [20]. The main objective of this study was therefore to document cIMT and distensibility in Class III obese subjects compared with a non-obese cohort, and to examine and compare traditional CVD risk factors (CVRF) and novel CVD biomarkers between the two populations. We hypothesized that cIMT and distensibility remain useful as CVD markers in the severely obese population despite technical difficulties that may be encountered and verified this by determining the association of cIMT and distensibility with other established CVRF in Class III obesity. Materials and Methods Ethics Statement The study protocol was approved by the institutional ethics committee of Alfred Healthcare (#158/06), and informed written consent was obtained from each participant. Study Population and Design A total of 96 subjects (31 non-obese controls: BMI 18.5 to 30.0 kg/m2 and 65 class III obesity: BMI.40.0 kg/m2) were included in the study. Class III obesity subjects were recruited via the Obesity Research Groups at Monash University while the ageand gender-matched non obese were from the Baker IDI BioBank database. Exclusion criteria were known coronary artery disease, cardiac failure, vascular brain disease, peripheral obstructive artery disease, significant renal or hepatic dysfunction and pregnancy. Subjects with current or past history of multiple myeloma, blood dyscrasia or any form of leukemia or lymphoma were also excluded. All individuals underwent a physical examination and had their medical histories recorded. In brief, participants were measured for height, weight, waist and hip circumferences and blood pressure. 30 ml of peripheral blood was drawn for routine blood tests following a 12 hr fast and also analyzed for levels of plasma adipokines, growth factors and cytokines, circulating angiogenic cells (CD133+/KDR+ PBMCs & Hill-CFU) and endothelial microparticles (EMP). Routine blood tests were performed by the Alfred Pathology Department including a full blood count, hsCRP, glucose and a lipid profile (HDL, LDL, total cholesterol and triglycerides). cIMT and distensibility were examined using non-invasive high resolution ultrasonography. The measurement of cIMT and distensibility were compared between the two groups. The associations of cIMT or distensibility with traditional CVRF (age, gender, BP, glucose and lipids etc) and adiposity/adipokines (BMI, waist:hip, adiponectin and leptin) we (...truncated)