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）危险因素聚集在一起时，发生CV疾病的风险大于单独因素的风险。同样，对儿童和青少年的尸检研究表明，心血管危险因素的聚集在临床事件发生之前就已经损害了心脏和血管。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（加速心血管老化）与心血管危险因素簇相关尚不清楚。此外，在确定个体或聚集性危险因素对CV老化的影响之前，必须先记录青年CV老化的正常速率。该建议的中心假设是，与苗条、低风险的受试者相比，随着时间的推移，具有心血管危险因素的年轻人，特别是那些伴有肥胖（如2型糖尿病）的年轻人，心血管老化（心脏和颈动脉增厚、心功能下降、动脉僵硬度增加、动脉壁功能降低）会发生得更快。这一假设将在5 - 7年后通过对一组已经收集了基线CV测量值（使用超声和其他非侵入性测试）的青少年和年轻人的重新检查进行验证。目的是1)测量青少年和年轻人的心血管老化率，2)确定哪些心血管危险因素最能预测心血管加速老化（心血管结构和功能的恶化）。本研究将通过提供使用非侵入性测试描述年轻人正常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危险因素，然后跟踪他们几十年直到他们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，可以建立基于证据的切入点，以确定何时应该开始对儿童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，即1)设定任意水平来定义异常危险因素水平，而不是基于硬CV数据；2)只处理高水平的单个危险因素，而不考虑处于边缘水平的CV危险因素群集对未来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目前儿童心血管预防的范式，从任意的治疗切入点之一转变为基于可靠科学研究的指导方针之一，其中儿童心血管的初级预防侧重于对有记录的心血管加速老化的青少年进行积极干预。