CV RISK FACTORS/VASCULAR FUNCTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 颈内动脉钙化常见于成人头颅常规CT扫描。它们与心血管危险因素密切相关&与血管造影血管狭窄相关，支持血管钙化是全身动脉粥样硬化的标记物的观点。即使是简单的牙科X光也可以识别与异常颈动脉超声有关的钙化，并预测后续的血管事件。儿童ICA钙化的重要性尚不清楚，尽管放射科医生经常在头部CT扫描中认出它们，一项小型儿科尸检研究发现此类病变的发病率很高。这些数据使我们假设，儿童的ICA钙化代表早期的动脉粥样硬化改变。我们将通过进行一项病例对照研究来验证这一理论，该研究从现有的接受过颞骨CT扫描的儿童数据库中选择受试者。这些扫描收集超过2年，由儿科放射科医生评估是否存在颈内动脉钙化。在408名儿童中，27%的儿童有钙化，尽管只有1名儿童的中等状况可能解释了这些发现(糖尿病和血脂异常)。50个病例和50个对照将进行研究，其中1/2的受试者年龄较小(6至12岁)，1/2的受试者年龄较大(12至19岁)，共100人。将收集人口统计学、病史和家族史、人体测量学和血压数据。实验室分析将包括钙、磷、血糖和胰岛素水平、空腹血脂、超敏C反应蛋白、同型半胱氨酸和纤维蛋白原。中心和外周血管部位的测试将包括颈动脉内中膜厚度和顺应性，主动脉增大指数，臂动脉扩张性和手臂、躯干和腿部的脉搏波速度。将进行分析，以确定患有ICA钙化的儿童是否1)表现出其他血管功能异常；2)心血管危险因素水平异常；以及3)血管异常是否与心血管危险因素水平相关。还将通过比较病例和对照组之间的钙磷产物、全身炎症、纤维蛋白原和同型半胱氨酸水平来探索早期血管钙化和功能障碍的潜在机制。这项拟议的研究将使我们能够确定血管钙化作为儿童早期动脉粥样硬化性疾病的标志的重要性，从而对高危人群进行更早的干预，以防止未来与心脏和中风相关的不良后果。

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.