Accelerated CV Aging in Youth Related to CV Risk Factor Clusters

项目摘要摘要 对成年人的长期随访显示，肥胖、高血压、胆固醇和血糖 增加未来心脏病发作和中风的风险。当这些心血管(CV)危险因素出现在 在集群中，心血管疾病的风险比增加基于个别因素的风险更大。同样， 对儿童和青少年的尸检研究表明，心血管危险因素集群损害心脏和血液 血管早在临床事件发生之前就出现了。超声波和其他类型的非侵入性研究是否可以 显示青少年和青少年的心脏损伤和动脉硬化(加速的心血管老化) 成人与心血管风险因素聚集性相关尚不清楚。此外，年轻人简历老化的正常速度必须 在个人或群集性风险因素对个人简历老化的影响可以确定之前，需要进行记录。 这一提议的中心假设是，更快的心血管老化(心脏和颈动脉更厚， 心功能下降，动脉僵硬增加，动脉壁功能降低)将随着时间的推移而发生在 有心血管危险因素的青少年，特别是那些伴有肥胖的青少年，如2型糖尿病，AS 与瘦的、低风险的受试者相比。这一假设将在5到7年后通过重新检查来检验， 一组青少年和青壮年，他们的基线CV测量(使用超声波和其他非 侵入性测试)已经被收集。其目的是：1)测量青少年的心血管衰退率和 年轻人和2)确定哪组心血管风险因素最能预测心血管加速老化 (血管结构和功能恶化)。 这项研究将通过提供描述年轻人正常简历衰老率的数据来解决一个知识缺口 使用非侵入性测试。这种方法很有价值，因为在以下情况下测量CV风险因素是不切实际的 然后跟随他们几十年，直到他们经历心脏病发作或中风。使用这些非- 作为侵入性测试的结果，可以制定基于证据的切入点来确定何时侵袭性 针对儿科心血管危险因素的治疗(如药物治疗)应开始。这将改善目前的 指导方针：1)设置任意级别，定义不基于硬简历的异常风险因素级别 数据和2)只在高水平上处理单个风险因素，而不考虑以下集群的贡献 临界水平的心血管危险因素对未来心血管疾病的风险。此外，如果被证明有效地识别 加速心血管老化，这些非侵入性测试可用于监测治疗效果。成功 该项目的完成将改变目前儿科心血管疾病预防的范式，从随意切割到 根据可靠的科学研究得出的治疗要点之一，其中初级心血管疾病预防 儿童将积极干预的重点放在有证据表明简历加速老化的年轻人身上。

Project Summary Abstract Long term follow-up of adults has shown that obesity, and high blood pressure, cholesterol and blood sugar increase the risk for future heart attack and stroke. When these cardiovascular (CV) risk factors occur in clusters, the risk for CV disease is greater than if the risk based on individual factors were added. Similarly, autopsy studies in children and adolescents show that clusters of CV risk factors damage the heart and blood vessels well before clinical events occur. Whether ultrasound and other types of non-invasive studies can demonstrate cardiac damage and hardening of the arteries (accelerated CV aging) in adolescents and young adults related to CV risk factor clusters is not known. Furthermore, the normal rate of CV aging in youth must be documented before the effect of individual or clustered risk factors for CV aging can be established. The central hypothesis for this proposal is that more rapid CV aging (thicker heart and carotid arteries, decreased cardiac function, increased arterial stiffness, reduced arterial wall function) will occur over time in youth with CV risk factors, especially those that cluster with obesity such as type 2 diabetes mellitus, as compared to lean, low-risk subjects. This hypothesis will be tested by re-examination 5 to 7 years later, of a group of adolescents and young adults in whom baseline CV measurements (using ultrasound and other non- invasive tests) were already collected. The aims are to 1) measure the rate of CV aging in adolescents and young adults and 2) determine which clusters of CV risk factors best predict accelerated CV aging (deterioration in CV structure and function). This study will address a knowledge gap by providing data describing the rate of normal CV aging in youth using non-invasive tests. This approach is valuable because it is impractical to measure CV risk factors in children and then follow them for decades until they experience heart attack or stroke. Using these non- invasive tests as the outcome, evidence-based cut-points can be developed to determine when aggressive treatment (like drug therapy) for pediatric CV risk factors should be initiated. This will improve upon the current guidelines which 1) set arbitrary levels defining an abnormal risk factor level that are not based on hard CV data and 2) only address a single risk factor at high level and do not account for the contribution of clusters of CV risk factors at borderline levels to risk for future CV disease. Furthermore, if proven effective in identifying accelerated CV aging, these non-invasive tests can be used to monitor effectiveness of treatment. Successful completion of this project will change the current paradigm in pediatric CV prevention from one of arbitrary cut- points for treatment to one of guidelines based on sound scientific study where primary CV prevention in children focuses aggressive intervention on youth with documented accelerated CV aging.