Vascular Remodeling in Overweight and Obese Adolescents

超重和肥胖青少年的血管重塑

• 批准号: 9129765
• 负责人: Justin P.V. Zachariah
• 金额: $ 16.44万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-06 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9129765
• 关键词: 18 year old; Adolescent; Adolescent obesity; Adult; Age; Age-Years; Aldosterone; Arteries; Attenuated; Award; Biochemical; Biological; Biological Markers; Biophysics; Blood Pressure; Blood Vessels; Body Weight decreased; Body mass index; C-reactive protein; Caliber; Cardiology; Cardiovascular Diseases; Cardiovascular system; Characteristics; Child; Childhood; Cholesterol; Clinical; Clinical Trials; Coronary heart disease; Country; Data; Diabetes Mellitus; Disease; Echocardiography; Event; Funding; Future; Glucose; Hypertension; Inflammation; Insulin; Insulin Resistance; Intake; Intervention; Isolated systolic hypertension; Leptin; Leptin resistance; Link; Measures; Mechanics; Mediating; Mediator of activation protein; Medical; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentorship; Obesity; Overweight; Pathway interactions; Patients; Pediatric cardiology; Peripheral Resistance; Phenotype; Physiologic pulse; Positioning Attribute; Prevalence; Pulse Pressure; Quality of life; Renin; Research; Research Personnel; Research Project Grants; Research Technics; Resources; Risk; Risk Factors; Risk stratification; Role; Structure; System; Testing; Time; Training; Translational Research; United States National Institutes of Health; Variant; Vascular remodeling; Weight; Work; arterial stiffness; cardiovascular disorder risk; catalyst; circulating biomarkers; cost effectiveness; electric impedance; hemodynamics; high risk; improved; indexing; mortality; secondary analysis; secondary outcome; tonometry

DESCRIPTION (provided by applicant): Large-artery vascular remodeling, such as arterial stiffening and dilation, is a biophysical antecedent to hypertension in adults. Emerging data in children identifies vascular remodeling as a feature of obesity, which is associated with present and future hypertension. Dr. Zachariah's research project examines the central hypothesis that excess weight in adolescents is related to vascular remodeling by assessing cross-sectional correlation as well as longitudinal change after weight loss. Using a combined tonometry-echocardiography system, Specific Aim 1 explores the hypothesis that excess weight will be associated with higher conduit arterial stiffness as indexed by central pulse pressure (PP), forward pulse wave (FPW), characteristic impedance (Zc) and carotid femoral pulse wave velocity (CFPWV), as well as with arterial dilation as indexed by larger effective aortic diameter (Da). Peripheral resistance (Zo) will be lower leading to higher pulse wave reflection as indexed by global reflection coefficient (RC). Secondary hypotheses include that a) the majority of the variation in central PP will be due to FPW, and b) the association between excess weight and vascular remodeling will be attenuated by circulating markers of insulin resistance, leptin resistance, inflammation, and aldosterone-to-renin ratio. Specific Aim 2 examines the effect of 2 months of weight loss on arterial stiffness and pulsatile load in 54 excess weight adolescents 13-18 attending a summer weight loss camp The educational component of this K23 award will include hands-on training in vascular testing and didactic course- work in analysis of biomarkers, analysis of multiple biomarker "-omic" platforms, and clinical trials. Mentorship will come from Drs. Jane Newburger, Vasan Ramachandran, and Gary Mitchell who have specific expertise in pediatric cardiovascular disease (CVD), adult CVD, circulating biomarkers in CVD, and vascular phenotypes in CVD. Enhanced by support from the NIH-sponsored Harvard Catalyst Clinical Translational Science Unit and the Department of Cardiology, the proposed K23 award will provide structured mentorship, protected research time, and training in modular, broadly applicable cardiovascular research techniques. The award will position Dr. Zachariah to be one of the few independently-funded pediatric cardiology clinical researchers in the country studying vascular medicine in high-risk children.

描述（由申请人提供）：大动脉血管重塑，例如动脉硬化和扩张，是成人高血压的生物物理学前因。儿童的新数据表明，血管重塑是肥胖的一个特征，这与当前和未来的高血压有关。 Zachariah 博士的研究项目通过评估横截面相关性以及减肥后的纵向变化，检验了青少年体重过重与血管重塑相关的中心假设。具体目标 1 使用联合张力测量-超声心动图系统，探讨了这样的假设：体重过重与较高的导管动脉硬度相关，如中心脉压 (PP)、前向脉搏波 (FPW)、特征阻抗 (Zc) 和颈动脉股动脉硬度脉搏波速度 (CFPWV)，以及以较大的有效主动脉直径 (Da) 为指标的动脉扩张。外围电阻 (Zo) 较低，导致脉搏波反射较高，如全局反射系数 (RC) 所示。次要假设包括 a) 中枢 PP 的大部分变化将归因于 FPW，b) 胰岛素抵抗、瘦素抵抗、炎症和醛固酮等循环标志物将减弱超重与血管重塑之间的关联。 -肾素比率。具体目标 2 检查 2 个月的减肥对参加夏季减肥营的 54 名 13-18 岁超重青少年的动脉僵硬度和脉动负荷的影响 该 K23 奖项的教育部分将包括血管测试和教学方面的实践培训课程-生物标志物分析、多种生物标志物“-omic”平台分析以及临床试验。指导将来自博士。 Jane Newburger、Vasan Ramachandran 和 Gary Mitchell 在儿科心血管疾病 (CVD)、成人 CVD、CVD 循环生物标志物和 CVD 血管表型方面拥有专业知识。在 NIH 赞助的哈佛催化剂临床转化科学单位和心脏病学系的支持下，拟议的 K23 奖项将提供结构化指导、受保护的研究时间以及模块化、广泛适用的心血管研究技术的培训。该奖项将使 Zachariah 博士成为该国为数不多的独立资助的儿科心脏病学临床研究人员之一，研究高危儿童的血管医学。

项目成果

Pulsatile and Steady-State Pressure Trends in Children: A Window into the Future?

儿童的脉动和稳态压力趋势：通向未来的窗口？

• DOI: 10.1159/000371620
• 发表时间: 2014
• 期刊: Pulse (Basel, Switzerland)
• 作者: Zachariah,JustinP;Kovacikova,Gabriela
• 通讯作者: Kovacikova,Gabriela

Linking pediatric obesity to subclinical alterations in cardiac structure and function.

将儿童肥胖与心脏结构和功能的亚临床改变联系起来。

• DOI: 10.1016/j.jcmg.2014.09.006
• 发表时间: 2014
• 期刊: JACC. Cardiovascular imaging
• 作者: Zachariah,JustinP;Ingul,CharlotteB;Marx,GeraldR
• 通讯作者: Marx,GeraldR

Pulse wave reflection in children: amplification through the lifecourse.

儿童脉搏波反射：生命历程中的放大。

• DOI: 10.1097/hjh.0000000000001357
• 发表时间: 2017
• 期刊: Journal of hypertension
• 影响因子: 4.9
• 作者: Zachariah,JustinP

Update: ambulatory blood pressure monitoring in children and adolescents: a scientific statement from the American Heart Association.

• DOI: 10.1161/hyp.0000000000000007
• 发表时间: 2014-05
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: Flynn JT;Daniels SR;Hayman LL;Maahs DM;McCrindle BW;Mitsnefes M;Zachariah JP;Urbina EM;American Heart Association Atherosclerosis, Hypertension and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young
• 通讯作者: American Heart Association Atherosclerosis, Hypertension and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young

Cardiovascular Health Promotion in Children: Challenges and Opportunities for 2020 and Beyond: A Scientific Statement From the American Heart Association.

• DOI: 10.1161/cir.0000000000000441
• 发表时间: 2016-09-20
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Steinberger J;Daniels SR;Hagberg N;Isasi CR;Kelly AS;Lloyd-Jones D;Pate RR;Pratt C;Shay CM;Towbin JA;Urbina E;Van Horn LV;Zachariah JP;American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; Council on Functional Genomics and Translational Biology; and Stroke Council
• 通讯作者: American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; Council on Functional Genomics and Translational Biology; and Stroke Council