Author ListRichard S Liu* MBBS 1Sophie E Dunn* MDAnneke Grobler PhDGreta Goldsmith BScNick Amanatidis BScChristina Benke BScKatherine Lange PhDMarkus Juonala PhDMelissa Wake MDDavid Burgner PhDon behalf of LSAC's Child Health CheckPoint Investigator GroupAffliations1 Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia* RS Liu and SE Dunn contributed equally to this work.Correspondence to:Name, Institute, Address, Phone, EmailAbstractObjectives: clear statement of main study aim and major hypothesis/research questionDesign: e.g. prospective, randomised, blinded, case controlSetting: level of care e.g. primary, secondary; number of participating centres. Generalise; don’t use the name of a specific centre, but give geographical location if importantParticipants: numbers entering and completing the study; sex and ethnic group if appropriate. Clear definitions of selection, entry and exclusion criteriaPrimary and secondary outcome measures: planned (i.e. in the protocol) and those finally measured (if different, explain why) – for quantitative studies onlyResults: main results with (for quantitative studies) 95% confidence intervals and, where appropriate, the exact level of statistical significance and the number need to treat/harm. Whenever possible, state absolute rather than relative risksConclusions: primary conclusions and their implications, suggest areas for further research if appropriateKeywords: Max 5, MESH terms https://www.nlm.nih.gov/mesh/meshhome.html , CheckPointArticle summaryStrengths and limitations of the study.Up to 5 dot points, no longer than one sentence each, that relate specifically to the methods of the study reportedThey should not include the results of the studyIntroductionA disease of long gestation and slow progression beginning in childhood, atherosclerosis offers multiple opportunities for prevention and early intervention (1-5). Enhancing our knowledge of risk prediction, stratification and reversibility are vitally important. Traditional cardiovascular (CVD) risk factors are imperfect markers of disease or risk prediction (6). Even the most widely-used CVD screening tools for adults (such as the Framingham Risk Score) predict at best 60-65% of cardiovascular risk (6), which translates into unacceptably low sensitivity, specificity, negative and positive predictive values. Newer measures, such as carotid intima-media thickness (cIMT), improves CVD risk prediction and stratification for intermediate-risk individuals (6), and allows early recognition of pathological changes (7). Early detection has the potential to moderate progression of atherosclerosis to CVD.Carotid intima-media thickness (cIMT) is a non-invasive ultrasound technique, which measures the thickness of the intimal and medial layers of the carotid arteries and is a marker of early subclinical total atherosclerotic burden (8-13). Carotid IMT is a useful composite marker because it is non-invasive, reflects multiple cardiovascular risk factors (14), indicates an individual’s current burden of atherosclerosis (15), predicts future cardiovascular events (include stroke and myocardial infarction) (8-13). (16-18) and has the potential to be used as a CVD screening tool in addition to existing risk scores (6, 19).Very little is known about the epidemiology and distribution of cIMT in the Australian population, limiting its utility for screening and risk evaluation. Intima-media thickness varies along a continuum (20) and as yet there are no agreed cIMT cutpoints tied to specific prevention or management recommendations. Furthermore it is unclear which patients would benefit from screening, when screening should be performed, and what the cost-benefit analysis would show (7).Even less epidemiological information is available for children. The Framingham Risk Score applies only to adults, and there are no data to demonstrate improved risk stratification from the addition of cIMT to existing paediatric risk scores (21). The use of cIMT to predict CVD may be particularly important for children, who have greater potential than adults for permanent reduction in cIMT progression with improved lifestyle and other modification of CVD risk (22, 23). Strength of cIMT associations within families may help predict cIMT, and hence CVD risk, of a child born to parents with high cIMT and also help targeted individuals to be screened. To date there are no population-based data regarding concordance of cIMT between parents and their offspring.The LSAC Child Health CheckPoint offers a unique opportunity to address these epidemiological gaps by cross-sectional measurement of cIMT in Australian parent-child dyads. This study aims firstly to map cIMT distribution in a population-representative sample of 11-12 year old Australian children and their parents, and secondly to measure (a) the extent of concordance within the parent-child dyads and (b) evidence for any non-linear associations.MethodsEthics and inclusion criteriaThe CheckPoint data collection protocol was approved by The Royal Children’s Hospital (Melbourne, Australia) Human Research Ethics Committee (33225D) and The Australian Institute of Family Studies Ethics Committee (14-26). The attending parent provided written informed consent for them and their child to participate in the study. Carotid IMT, lumen diameter, height, weight and puberty status were collected at a specialized CheckPoint assessment centre visit. Those families who could not arrange a visit were offered a home visit with a reduced protocol excluding carotid ultrasound.Participating families were included in the current analyses if carotid IMT data from CheckPoint were available (Figure 1). This meant all participants undertook an assessment centre visit.ProcedureParticipants underwent carotid ultrasound, vascular stiffness assessment, and blood pressure measurement in a specialized 15-min station called Heart Lab, which was within the first hour of the 3.5 hour visit, pre-exercise testing and semi-fasted.Carotid artery ultrasoundCarotid artery images were acquired using standardized protocols developed in accordance with recommendations of the American Society of Echocardiography and Mannheim Consensus statements.(24, 25) All participants lay supine with their head turned 45 degrees to the left to expose the right side of neck. The right carotid artery was chosen to harmonize with other vascular measures taken in Heart Lab, such as pulse wave velocity, which also assessed the right-sided circulation. Ultrasound images were obtained using a portable ultrasound machine and 10 MHz linear array probe (Vivid-I, GE Healthcare, Chicago, IL, USA). The angle of imaging was chosen, in the absence of a Meijer Carotid Arc, by image quality, approximately 45 degrees to the midline angled such that the overlying internal jugular vein lay between the artery and the probe. A modified 3-lead ECG captured cardiac cycle information concurrently. Real-time B mode ultrasound cine-loops 10 cardiac cycles in length were captured in triplicate by one of four trained technicians.Image processing and qualityAll images were reviewed by one technician to select loops that met key optimisation parameters: a clear near and far wall intima-media, clear lumen, straight vessel, presence of the carotid bulb and an ECG trace. The best quality 5-7 cardiac cycle section of the loops were selected and trimmed. Quality of the trimmed images were graded for wall clarity; length of clarity; position of clarity relative to carotid blub; clear lumen; and straightness of vessel, on a subjective 1-4 scale.Mean and maximum risk intima-media thicknessThese loops were further processed using Carotid Analyzer (Medical Imaging Applications, Coralville, IA, USA), a commercially available semi-automatic edge detection software program. Intima-media thickness was measured approximately 10 mm proximal to the carotid bulb, over a distance of 5-10 mm. Raters calibrated the images vertically to 10mm and selected the vessel region of highest quality 10mm from the carotid bulb to then initiate a semi-automated measurement of the intima-media thickness. Each frame was then manually adjusted as needed or rejected if the intima-media interface was unclear or blurred.Carotid IMT values are presented as the mean of 3-5 still frames of IMT captured at end-diastole. We present both ‘mean’ carotid IMT measurements, which refer to the average from 3-5 frames of the entire carotid IMT measurement over the 5-10 mm section, as well as ‘maximum’ carotid IMT, which refer to the 3-5 frame mean of the thickest carotid IMT measurement over the 5-10 mm section.