Determinants of intima-media thickness in the young: The Avon Longitudinal Study of Parents and Children (ALSPAC)

Objectives: To characterize the determinants of cIMT in a large (n>4000) longitudinal cohort of healthy young people aged 9-21 years. Background: Greater carotid intima-media thickness (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 (age 9-17) and cross-sectional (age 17 and 21) 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 allowed investigation of the distinct layers (i.e. intima or media) which may underlie observed differences. Results: Fat-free mass (FFM) and systolic blood pressure (SBP) 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 [95% CI] = 0.007mm [0.004,0.010]; p<0.001), whereas fat mass (FM) was negatively associated (difference = -0.0032 [-0.004, -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 MAP when increases in body mass were attributable to increased FFM, but not FM. Risk factor-associated differences in 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 prior to adulthood.