Scott T Chiesa1, Marietta Charakida2, Georgios Georgiopoulos3, Frida Dangardt4, Kaitlin H Wade5, Alicja Rapala6, Devina J Bhowruth1, Helen C Nguyen1, Vivek Muthurangu7, Rukshana Shroff8, George Davey Smith5, Debbie A Lawlor5, Naveed Sattar9, Nicholas J Timpson5, Alun D Hughes10, John E Deanfield11. 1. Vascular Physiology Unit, UCL Institute of Cardiovascular Science, London, United Kingdom. 2. Vascular Physiology Unit, UCL Institute of Cardiovascular Science, London, United Kingdom; Division of Imaging Sciences and Biomedical Engineering, King's College London, United Kingdom. 3. 1st Department of Cardiology, National and Kapodistrian University of Athens, Hippokration Hospital, Athens, Greece. 4. Vascular Physiology Unit, UCL Institute of Cardiovascular Science, London, United Kingdom; Department of Paediatric Physiology, The Queen Silvia Children's Hospital, The Sahlgrenska Academy and University Hospital, Gothenburg, Sweden. 5. MRC Integrative Epidemiology Unit (IEU), The University of Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, United Kingdom. 6. Vascular Physiology Unit, UCL Institute of Cardiovascular Science, London, United Kingdom; Department of Population Science and Experimental Medicine, UCL Institute of Cardiovascular Science, London, United Kingdom. 7. Centre for Cardiovascular Imaging, UCL Institute of Cardiovascular Science, London, United Kingdom. 8. Vascular Physiology Unit, UCL Institute of Cardiovascular Science, London, United Kingdom; Nephrology Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom. 9. Institute of Cardiovascular and Medical Science, University of Glasgow, United Kingdom. 10. Department of Population Science and Experimental Medicine, UCL Institute of Cardiovascular Science, London, United Kingdom; MRC Unit for Lifelong Health and Ageing at UCL, London, United Kingdom. 11. Vascular Physiology Unit, UCL Institute of Cardiovascular Science, London, United Kingdom. Electronic address: j.deanfield@ucl.ac.uk.
Abstract
OBJECTIVES: This study characterized the determinants of carotid intima-media thickness (cIMT) in a large (n > 4,000) longitudinal cohort of healthy young people age 9 to 21 years. BACKGROUND: Greater cIMT is commonly used in the young as a marker of subclinical atherosclerosis, but its evolution at this age is still poorly understood. METHODS: Associations between cardiovascular risk factors and cIMT were investigated in both longitudinal (ages 9 to 17 years) and cross-sectional (ages 17 and 21 years) analyses, with the latter also related to other measures of carotid structure and stress. Additional use of ultra-high frequency ultrasound in the radial artery at age 21 years allowed investigation of the distinct layers (i.e., intima or media) that may underlie observed differences. RESULTS: Fat-free mass (FFM) and systolic blood pressure were the only modifiable risk factors positively associated with cIMT (e.g., mean difference in cIMT per 1-SD increase in FFM at age 17: 0.007 mm: 95% confidence interval [CI]: 0.004 to 0.010; p < 0.001), whereas fat mass was negatively associated with cIMT (difference: -0.0032; 95% CI: 0.004 to -0.001; p = 0.001). Similar results were obtained when investigating cumulative exposure to these factors throughout adolescence. An increase in cIMT maintained circumferential wall stress in the face of increased mean arterial pressure when increases in body mass were attributable to increased FFM, but not fat mass. Risk factor-associated differences in the radial artery occurred in the media alone, and there was little evidence of a relationship between intimal thickness and any risk factor. CONCLUSIONS: Subtle changes in cIMT in the young may predominantly involve the media and represent physiological adaptations as opposed to subclinical atherosclerosis. Other vascular measures may be more appropriate for the identification of arterial disease before adulthood.
OBJECTIVES: This study characterized the determinants of carotid intima-media thickness (cIMT) in a large (n > 4,000) longitudinal cohort of healthy young people age 9 to 21 years. BACKGROUND: Greater cIMT is commonly used in the young as a marker of subclinical atherosclerosis, but its evolution at this age is still poorly understood. METHODS: Associations between cardiovascular risk factors and cIMT were investigated in both longitudinal (ages 9 to 17 years) and cross-sectional (ages 17 and 21 years) analyses, with the latter also related to other measures of carotid structure and stress. Additional use of ultra-high frequency ultrasound in the radial artery at age 21 years allowed investigation of the distinct layers (i.e., intima or media) that may underlie observed differences. RESULTS: Fat-free mass (FFM) and systolic blood pressure were the only modifiable risk factors positively associated with cIMT (e.g., mean difference in cIMT per 1-SD increase in FFM at age 17: 0.007 mm: 95% confidence interval [CI]: 0.004 to 0.010; p < 0.001), whereas fat mass was negatively associated with cIMT (difference: -0.0032; 95% CI: 0.004 to -0.001; p = 0.001). Similar results were obtained when investigating cumulative exposure to these factors throughout adolescence. An increase in cIMT maintained circumferential wall stress in the face of increased mean arterial pressure when increases in body mass were attributable to increased FFM, but not fat mass. Risk factor-associated differences in the radial artery occurred in the media alone, and there was little evidence of a relationship between intimal thickness and any risk factor. CONCLUSIONS: Subtle changes in cIMT in the young may predominantly involve the media and represent physiological adaptations as opposed to subclinical atherosclerosis. Other vascular measures may be more appropriate for the identification of arterial disease before adulthood.
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