Longitudinal assessment of novel biomarkers for predicting cardiovascular disease in youth

用于预测青年心血管疾病的新型生物标志物的纵向评估

• 批准号: 8903870
• 负责人: Justin R. Ryder
• 金额: $ 5.24万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8903870
• 关键词: Address; Adolescent; Adult; Atherosclerosis; Biological Markers; Blood; Blood Vessels; Body fat; Cardiovascular Diseases; Cardiovascular system; Cellular biology; Child; Childhood; Clinical; Data; Disease Outcome; Disease Progression; Distress; Doctor of Philosophy; Early identification; Early treatment; Endothelial Cells; Event; Exhibits; Fatty acid glycerol esters; Funding; Future; Goals; Health; Individual; Life; Longitudinal Studies; Measures; Medial; Metabolic syndrome; Modeling; Morbid Obesity; Morbidity - disease rate; Normal Range; Obesity; Population; Predictive Value; Prevalence; Process; Research Infrastructure; Resources; Risk; Risk Factors; Scientist; Staging; Stratification; Structure; Thick; Time; Translating; United States; Vascular System; Visceral; Weight; Youth; arterial stiffness; burden of illness; cardiovascular disorder risk; career development; clinical practice; clinically relevant; endothelial dysfunction; high risk; innovation; mortality; novel; obesity in children; parent project; particle; peer; premature; public health relevance; success; tool

 DESCRIPTION (provided by applicant): Severe obesity (BMI =120% of the 95th percentile) afflicts nearly 6% of children and adolescents and continues to increase in prevalence. Youth with severe obesity are at serious risk for long-term health complications, particularly cardiovascular disease (CVD). Endothelial dysfunction is the earliest manifestation of the CVD process resulting in changes in vascular structure (carotid intima-medial thickness (cIMT)) and arterial stiffness (carotid incremental elastic modulus (cIEM)). In adults, increased cIMT and arterial stiffness are associated with CVD progression and predictive of future cardiovascular events. However, clinically relevant predictors of early subclinical atherosclerosis progression during childhood have yet to be identified, and traditional CVD risk factors are no better at predicting CVD progression than obesity status alone. Therefore, it is critical to identify novel biomarkers that will translate into clinical practice and are predictive of CVD progression. Biomarkers of endothelial cell biology, which include circulating endothelial cells (CECs) and endothelial micro-particles (EMPs), are hallmarks of advanced endothelial cell distress and may assist in identifying and tracking of youth at highest-risk for CVD. While CECs and EMPs have shown promise in adults, little data on CECs and EMPs exists in children and adolescents. Youth with severe obesity represent an ideal model for examining CECs and EMPs, as they exhibit elevated levels of CVD risk factors and are at increased risk for early CVD mortality. Moreover, we have strong cross-sectional data suggesting that severe obesity in children and adolescents is associated with adverse levels of these endothelial biomarkers. However, whether CECs and EMPs can predict changes in subclinical atherosclerosis over time has not been investigated. To answer these significant questions, the main aim of the proposed longitudinal study is to examine the predictive value of CECs and EMPs for identifying changes in subclinical atherosclerosis in youth ranging from normal weight to those with severe obesity. The primary hypothesis is that CECs and EMPs will be predictive of changes over time in cIMT and arterial stiffness across a spectrum of youth ranging from normal weight to severe obesity. Additionally, we hypothesize that youth with severe obesity will exhibit greater rates of change in cIMT, arterial stiffness, CECs, and EMPs than their normal weight and obese peers. This proposal will provide novel longitudinal data in youth with severe obesity to aid in characterizing the risk of the burgeoning problem. Furthermore, this proposal will provide new technical exposure and career development for the trainee, Justin Ryder, Ph.D., in his pursuit of becoming an independently federally-funded clinical translational scientist focused on CVD risk among youth with obesity.

 描述（由申请人提供）：重度肥胖（BMI = 95% 的 120%）困扰着近 6% 的儿童和青少年，并且患病率持续增加。重度肥胖的青少年面临着长期健康并发症的严重风险，尤其是。心血管疾病（CVD）是 CVD 过程的最早表现，导致血管结构（颈动脉内膜中层厚度（cIMT））和动脉僵硬度（颈动脉增量弹性模量（cIEM））。在成人中，cIMT 和动脉僵硬度的增加与 CVD 进展有关，并可预测未来的心血管事件。然而，儿童期早期亚临床动脉粥样硬化进展的临床相关预测因素尚未确定。传统的 CVD 危险因素在预测 CVD 进展方面并不比单独的肥胖状态更好，因此，确定可转化为临床实践并预测 CVD 进展的新型生物标志物至关重要。内皮细胞生物学的生物标志物，包括循环内皮细胞 (CEC) 和内皮微粒 (EMP)，是晚期内皮细胞窘迫的标志，可能有助于识别和跟踪 CVD 风险最高的青少年。在成人中已显示出希望，但在儿童和青少年中很少有关于 CEC 和 EMP 的数据，患有严重肥胖的青少年是检查 CEC 和 EMP 的理想模型，因为它们升高了 CVD 危险因素的水平，并且早期 CVD 死亡的风险增加。此外，我们有强有力的横截面数据表明，儿童和青少年的严重肥胖与这些内皮生物标志物的不良水平有关。尚未研究 CEC 和 EMP 可以预测亚临床动脉粥样硬化随时间的变化。从正常体重到严重肥胖的青少年的亚临床动脉粥样硬化主要假设是，CEC 和 EMP 将预测从正常体重到严重肥胖的一系列青少年的 cIMT 和动脉僵硬度随时间的变化。继续认为，患有严重肥胖症的青少年将表现出更大的变化率 cIMT、动脉僵硬度、CEC 和 EMP 均高于正常体重和肥胖同龄人。该提案将为严重肥胖的青少年提供新颖的纵向数据，以帮助表征。 此外，该提案将为实习生 Justin Ryder 博士提供新的技术接触和职业发展，帮助他成为一名独立的联邦政府资助的临床转化科学家，专注于青少年的 CVD 风险。与肥胖。