CV RISK FACTORS/VASCULAR FUNCTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Calcifications of the intra-cranial carotid arteries (ICA) are frequently found in adults on routine head CT scans. They correlate strongly with CV risk factors & are associated with angiographic vessel stenosis supporting the idea that vascular calcifications are a marker for generalized atherosclerosis. Even simple dental X-rays may identify calcifications which relate to abnormal carotid ultrasound & predict subsequent vascular events. The significance of ICA calcifications in children is not known eve though radiologist frequently recognize them on head CT scans and one small pediatric autopsy study found a high prevalence of such lesions. These data led us to hypothesize that ICA calcifications in children represent early atherosclerotic change. We will test this theory by performing a case-control study selecting subjects from an existing database of children who underwent a temporal bone CT scan. These scans collected over 2 years, were evaluated by Pediatric Radiologist for presence of ICA calcification. Of 408 children, 27% had calcification although only 1 had a medial condition that might explain the findings (diabetes and dyslipidemia). Fifty cases & fifty controls will be studies with 1/2 of the subject younger (6 to 12 years) and 1/2 older (12 to 19 years) for a total of 100. Demographics, medical and family history, anthropometrics & blood pressure data will be collected. Laboratory analyses will include calcium, phosphorus, glucose & insulin levels, fasting lipid panel, high sensitivity CRP, homocysteine & fibrinogen. Central & peripheral vascular sites tested will include carotid intimate-media thickness & compliance, aortic augmentations index, brachial artery distensibility & pulse wave velocity to the arm, trunk & leg. Analyses will be performed to determine if children with ICA calcification 1) demonstrate other abnormalities in vascular function; 2) have abnormal levels of CV risk factors; and 3) whether vascular abnormalities correlate with levels of CV risk factors. Potential mechanisms underlying early vascular calcifications and dysfunction will also be explored by comparing calcium-phosphate product, levels of systemic inflammation, fibrinogen and homocysteine between cases & controls. The proposed research will allow us to determine the importance of vascular calcification as a marker for early atherosclerotic disease in children allowing earlier intervention in high risk individuals to prevent future adverse cardiac and stroke-related outcomes.