Accelerated CV Aging in Youth Related to CV Risk Factor Clusters

与心血管危险因素群相关的青少年心血管加速老化

• 批准号: 8023440
• 负责人: Elaine Mott Urbina
• 金额: $ 57.5万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8023440
• 关键词: Acceleration; Accounting; Address; Adolescent; Adult; Affect; African American; Age; Aging; Arterial Fatty Streak; Arteries; Atherosclerosis; Autopsy; Behavior Therapy; Benchmarking; Blood Glucose; Blood Vessels; Cardiac; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Caucasians; Caucasoid Race; Child; Childhood; Cholesterol; Clinical; Coronary artery; Cross-Sectional Studies; Data; Deterioration; Development; Diabetes Mellitus; Ethics; Evaluation; Event; Funding; Future; Guidelines; Heart; Hypertension; Image; Individual; Insulin Resistance; Intervention; Knowledge; Lead; Left Ventricular Mass; Lipids; Measurement; Measures; Monitor; Myocardial Infarction; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Outcome Measure; Patients; Pharmacotherapy; Population; Prevention; Prevention Guidelines; Relative (related person); Research; Risk; Risk Factors; Risk Reduction; Stroke; Structure; Testing; Thick; Time; Treatment Effectiveness; Ultrasonography; United States National Institutes of Health; Withholding Treatment; Youth; arterial stiffness; base; cardiovascular disorder risk; cardiovascular risk factor; cohort; design; diabetic; evidence base; experience; follow-up; high risk; illness length; improved; innovation; intima media; lifetime risk; prevent; prospective; sound; successful intervention; young adult

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.

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）风险因素成簇发生时，CV疾病的风险大于基于个体因素的风险。同样，儿童和青少年的尸检研究表明，在临床事件发生之前，CV风险因素的集群就会损害心脏和血管。目前尚不清楚超声和其他类型的非侵入性研究是否可以证明青少年和年轻人的心脏损伤和动脉硬化（加速CV老化）与CV风险因素簇相关。此外，在确定CV老化的单个或聚集风险因素的影响之前，必须记录青年CV老化的正常速率。该建议的中心假设是，与瘦的低风险受试者相比，随着时间的推移，具有CV风险因素的年轻人，特别是那些与肥胖（如2型糖尿病）相关的年轻人，将发生更快的CV老化（心脏和颈动脉增厚，心脏功能下降，动脉僵硬度增加，动脉壁功能降低）。将在5 - 7年后对一组已收集基线CV测量值（使用超声和其他非侵入性检查）的青少年和年轻成人进行重新检查，以检验这一假设。目的是1）测量青少年和年轻人的CV老化率，2）确定哪些CV风险因素簇最能预测加速CV老化（CV结构和功能恶化）。这项研究将通过使用非侵入性测试提供描述青年正常CV老化率的数据来解决知识差距。这种方法是有价值的，因为测量儿童的心血管风险因素，然后跟踪他们几十年，直到他们经历心脏病发作或中风是不切实际的。使用这些非侵入性检查作为结局，可以制定循证临界点，以确定何时应开始针对儿童CV风险因素的积极治疗（如药物治疗）。这将改进当前指南，该指南1）设定了定义异常风险因素水平的任意水平，而不是基于硬CV数据，2）仅解决了高水平的单一风险因素，而没有考虑临界水平的CV风险因素簇对未来CV疾病风险的贡献。此外，如果证明有效识别加速CV老化，这些非侵入性测试可用于监测治疗的有效性。该项目的成功完成将改变儿科CV预防的当前模式，从任意治疗临界点之一转变为基于可靠科学研究的指南之一，其中儿童的主要CV预防侧重于对有记录的CV加速老化的青少年进行积极干预。 公共卫生关系：在成年人中，肥胖和高血压、胆固醇和血糖等心血管（CV）风险因素增加了心脏病发作和中风的机会。该项目建议使用超声和其他非侵入性测试来证明加速CV老化（心脏损伤和动脉硬化）发生在与CV风险因素簇相关的青少年和年轻人中。本项目的成功完成可能会产生更准确的指南，以确定何时应开始针对儿童CV风险因素的积极治疗（如药物治疗），以预防未来的CV疾病。