Accelerated CV Aging in Youth Related to CV Risk Factor Clusters

描述(由申请人提供)：对成年人的长期随访表明，肥胖、高血压、胆固醇和血糖会增加未来心脏病发作和中风的风险。当这些心血管(CV)风险因素成群出现时，心血管疾病的风险比增加基于单个因素的风险更大。同样，对儿童和青少年的尸检研究表明，在临床事件发生之前，一连串的心血管危险因素就会损害心脏和血管。超声和其他类型的非侵入性研究是否能显示青少年和年轻人的心脏损害和动脉硬化(加速的心血管老化)与心血管风险因素簇有关尚不清楚。此外，必须记录青年心血管老化的正常比率，然后才能确定单个或聚集的心血管老化危险因素的影响。这一建议的中心假设是，与瘦弱、低风险的受试者相比，随着时间的推移，有心血管危险因素的年轻人将发生更快的心血管老化(心脏和颈动脉增厚、心功能下降、动脉僵硬增加、动脉壁功能下降)，特别是那些伴有肥胖的年轻人，如2型糖尿病。这一假设将在5到7年后通过对一组已经收集了基线CV测量(使用超声波和其他非侵入性测试)的青少年和年轻人的重新检查来验证。其目的是1)测量青少年和年轻人的心血管衰老率，以及2)确定哪组心血管风险因素最能预测心血管老化加速(心血管结构和功能的恶化)。这项研究将通过使用非侵入性测试提供描述青年正常心血管衰老率的数据来解决知识差距。这种方法很有价值，因为测量儿童的心血管危险因素，然后对它们进行数十年的跟踪，直到他们经历心脏病发作或中风是不切实际的。使用这些非侵入性测试作为结果，可以开发基于证据的切入点，以确定何时应该开始对儿科心血管危险因素进行积极治疗(如药物治疗)。这将改进目前的指南，该指南1)设置任意水平，定义不基于硬心血管数据的异常风险因素水平，以及2)仅针对高水平的单个风险因素，并且没有考虑处于临界水平的心血管风险因素集群对未来心血管疾病风险的贡献。此外，如果这些非侵入性测试被证明在识别加速的心血管老化方面有效，则可以用于监测治疗的有效性。该项目的成功完成将改变目前儿科心血管疾病预防的范例，从任意的治疗切入点之一，转变为基于可靠的科学研究的指南之一，其中儿童心血管疾病的初级预防侧重于对有证据表明心血管加速老化的青年进行积极干预。 与公共健康相关：在成年人中，肥胖和高血压、胆固醇和血糖等心血管(CV)危险因素集群增加了心脏病发作和中风的机会。该项目建议使用超声波和其他非侵入性测试来证明心血管老化加速(心脏损伤和动脉硬化)发生在与心血管风险因素簇相关的青少年和年轻人中。该项目的成功完成可能会带来更准确的指南，以确定何时应该开始对儿科心血管危险因素进行积极治疗(如药物治疗)，以预防未来的心血管疾病。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: In adults, clusters of cardiovascular (CV) risk factors such as obesity and high blood pressure, cholesterol and blood sugar increase the chances for heart attack and stroke. This project proposes to use ultrasound and other non-invasive tests to prove that accelerated CV aging (cardiac damage and hardening of the arteries) occurs in adolescents and young adults related to CV risk factor clusters. Successful completion of this project may lead to more accurate guidelines to determine when aggressive treatment (like drug therapy) for pediatric CV risk factors should be initiated to prevent future CV disease.