Age Associated Changes In Structural And Functional Cardio-Vascular Properties

与年龄相关的心血管结构和功能的变化

• 批准号: 10913152
• 负责人: Edward Lakatta
• 金额: $ 2.02万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10913152
• 关键词: ACE2; Acceleration; Age; Age Years; Aging; American Heart Association; Ankle; Aorta; Baltimore; Biomedical Engineering; Blood Pressure; Blood Vessels; Body Size; Bone Density; COVID-19 mortality; Cardiac; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Central obesity; Characteristics; Clinical; Collaborations; Communities; Complex; Computer software; Coronary; Coupling; Data; Dilatation - action; Disease; EFRAC; Early Intervention; Echocardiography; Elderly; Endothelium; Environment; Fatty acid glycerol esters; Functional disorder; Gender; Genes; Genetic; Genetic Determinism; Genome; Geometry; Health; Heart failure; Human; Hypertension; Hypothyroidism; Individual; Inflammation; Insulin-Like Growth Factor I; International; Intramural Research Program; Ipsilateral; Laboratories; Left ventricular structure; Leg; Life Style; Light; Longitudinal Studies; Lower Extremity; Magnetic Resonance Imaging; Manuscripts; Measurement; Measures; Mechanics; Medial; Mission; Mitochondria; Modification; Muscle; Myocardial; Nature; Obesity; Outcome; Paper; Participant; Pattern; Perfusion; Peripheral arterial disease; Persons; Phenotype; Physiologic pulse; Physiological; Population; Postdoctoral Fellow; Prevention strategy; Process; Production; Property; Publications; Publishing; Reporting; Research; Research Project Grants; Risk Factors; Role; Sardinia; Signal Transduction; Structure; Taiwan; Testing; Thick; Thigh structure; Time; Training; Triglycerides; Uric Acid; Ventricular; Visceral; Visit; Vitamin D; Woman; Work; Writing; age related; arterial stiffness; body system; calcification; cardiovascular risk factor; cognitive function; cohort; comorbidity; coronary calcium scoring; electric impedance; follow-up; functional status; gender difference; genetic element; heart function; improved; indexing; insight; intimal medial thickening; longitudinal analysis; masked hypertension; mathematical analysis; meetings; men; neglect; novel; older patient; preservation; pressure; prevent; programs; rate of change; recruit; sex; subcutaneous; tonometry; trait; translational study; validation studies

I. Patterns and Determinants of CV Aging: A. We published a paper examining the relationship between longitudinal changes in the ankle-brachial index and muscle energy production in a community-dwelling population free of peripheral arterial disease. We find that a greater decline in ABI over time, but not baseline ABI, was associated with a faster decline in thigh mitochondrial oxidative capacity in the ipsilateral leg. Further studies are needed to examine whether early interventions that improve lower extremity muscle perfusion can improve and prevent the decline of muscle energetics. (Oberdier 2022). B. We published a paper examining the association between baseline carotid geometric phenotype and longitudinal changes in arterial stiffness. We found that dilated hypertrophic carotid geometric phenotype was associated with accelerated arterial sickening over time compared to other phenotypes. The dilated hypertrophic phenotype group has a greater age-specific arterial dilation, wall thickening, and stiffness (the arterial aging triad). This suggests that this phenotype is a form of accelerated aging that might explain the worse clinical outcomes observed in this group (AlGhatrif 2023) C. We also published a paper exploring the relationship between the longitudinal changes in arterial and cardiac function with aging. We revealed this paper revealed in uncoupling between increased arterial loading due to stiffening with aging and increasing ventricular contractility/stiffness. Progressive AV uncoupling occurred with aging and was more pronounced in women than men. While Ea change did not differ by sex, Elv increased at a slower rate in women than in men. AV uncoupling was inversely associated with EDV and SV rates of change and directly associated with an increase in ESV rate of change. Additional studies are needed to explore the functional consequences of AV uncoupling in healthy individuals with respect to the emergence of age-associated clinical cardiovascular diseases, such as heart failure with preserved ejection fraction. (AlGhatrif 2021) Previous work: D. We published a paper showing age-associated differences in ACE2 levels, which is implicated in high COVID-19-related mortality in older patients with CV comorbidities (AlGhatrif 2021) E. We participated in a research project aiming at building a global phenotypic metric of aging using various parameters, including CV ones. (Kuo 2020) F. A publication using data from Taiwan study has shown that wave reflection parameters, but not arterial stiffness were associated with greater BP variability (Hsu, 2017)New findings from the BLSA have shown longitudinal association between uric acid and pulse wave velocity (Canepa, 2016); this association was observed in men but not women. These findings shed light into the previously observed gender differences in arterial stiffening with aging. Previous findings from the Sardinia study have shown no effect of subclinical hypothyroidism on intimal medial thickness, a manifestation of arteria aging (Delitala, 2016) F. Previous findings from the SardiNIA study reported Gender specific profiles of white coat and masked hypertension impacts on arterial structure and function (Scuteri 2016) Previous findings from SardiNIA project have shown significant gender differences in the effect of white coat and masked hypertension on arterial structure (Scuteri 2016). Previous Longitudinal insight into the complex nature of arterial aging. Findings from the Baltimore Longitudinal Study on Aging (BLSA) revealed a non-linear, longitudinal increase in pulse wave velocity (PWV) with aging that is more pronounced in men (AlGhatrif et al., 2013). Analysis of longitudinal data from SardiNIA project showed similar results, but in addition it showed an interesting separation between the longitudinal trajectories of PWV and SBP in men with advancing age (Scuteri 2014); this suggests that other age-related process, such as aortic dilatation, might blunt the effect of wall stiffening and cause the separation of PWV and SBP. These findings were reviewed along with other reports in a review article published in Current Hypertension Reports (AlGhatrif and Lakatta 2015). B. Genetic and Environmental Underpinnings of Accelerated Cardiovascular Aging -Genetic determinates: Earlier results from the SardiNIA study have revealed a potential role of the Col4A1 gene (Tarasov 2009) and a second genetic element located in a desert region of the genome (Mitchell 2012), findings which have been confirmed in replication studies and larger Consortia-based analysis. Work is in progress to examine genetic determinants of the longitudinal change in PWV. -Environmental determinants: Another report using SardiaNIA cohort showed no evidence of an effect o f subclinical hypothyroidism on arterial stiffness (Delitala 2015). Except for blood pressure, we have previously found a minimal role of traditional cardiovascular risk factors in the progression of arterial stiffness (AlGhatrif et al., 2013). We have also found that central obesity might introduce bias to PWV measurements (Canepa et al. 2014). In addition, we have found that vitamin D modulates the association of circulating insulin-like growth factor-1 with carotid artery intima-media thickness (Ameri et al. 2014). We have also found that bone mineral density plays a role in the inverse relationship between body size and aortic calcification (Canepa et 2014). Projects examining the role of low-grade inflammation in arterial stiffness using data from the BLSA and the SardiNIA projects are in progress. As far as cardiac funciton, Results from the BLSA have shown that visceral, rather than subcutaneous fat, is associated with worse myocardial diastolic dysfunction (M Canepa, Strait, et al., 2013. In addition, the VALIDATE study, which will assess the factors leading to unhealthy vascular aging as measured by PWV, intimal medial thickness, coronary calcium scoring, among other tests, is currently in final stages of completing the follow-up visit. Another project has been started aiming to assess age-associated changes in regional adiposity and novel cardiovascular risk factors such as coronary endothelial function and myocardial triglyceride content using magnetic resonance imaging. II. Advanced CV phenotyping: To further examine the complex nature of arterial aging, we have initiated a program focused on advanced mathematical analysis of cardiovascular physiological signals including pressure, flow, and geometry signals to derive parameters that better represent the functional status of the CV in a given person and how it changes with aging. We recruited a post-doctoral fellow with training in biomedical engineering and established collaborations with international experts to develop advanced software to analyze CV traits collected from BLSA and SardiNIA participants. Great efforts have been made to compile raw data from echocardiography, Doppler, and applanation tonometry. Variables generated include derived central blood pressures, wave reflection parameters, aortic and carotid characteristic impedance, carotid geometric phenotype, carotid total, systolic, and diastolic flow rates, and CV mechanical power and efficiency. Preliminary data have showed that cardiac efficiency declines with aging and that this decline is attributed in part to increased aortic impedance and early arrival of wave reflection, but with reflection magnitude per se. These results were accepted for presentation at the American Heart Association meeting 2016. A more comprehensive analysis is being performed and a manuscript will be written. III. The impact of arterial aging on cardiac geometry and function: A recent analysis of the Health ABC study has shown that arterial stiffness was not an independent risk factor for heart failure (Pandey, 2017)

I.简历衰老的模式和决定因素： 答：我们发表了一篇论文，研究了无周围动脉疾病的社区居民中脚踝 - 野蛮指数的纵向变化与肌肉能量产生之间的关系。我们发现，随着时间的流逝，ABI的下降量较大，但基线ABI的下降与同侧腿的大腿线粒体氧化能力的更快下降有关。需要进一步的研究来检查改善下肢肌肉灌注的早期干预措施是否可以改善并防止肌肉能量学的下降。 （Oberdier 2022）。 B.我们发表了一篇论文，研究了基线颈动脉几何表型与动脉刚度的纵向变化之间的关联。我们发现，与其他表型相比，肥厚的颈动脉几何表型随着时间的流逝加速了动脉恶心。扩张的肥厚表型组具有更大的年龄特异性动脉扩张，壁增厚和刚度（动脉衰老三合会）。这表明这种表型是一种加速衰老的形式，可以解释该组中观察到的临床结果较差（Alghatrif 2023） C.我们还发表了一篇论文，探讨了动脉功能与衰老的纵向变化之间的关系。我们揭示了本文揭示了由于随着衰老而加强和增加心室收缩力/僵硬而增加动脉负荷之间的解耦。渐进的AV解偶联发生在衰老中，女性比男性更为明显。尽管性别的变化没有差异，但女性的ELV比男性较慢。 AV解偶联与EDV和SV变化率成反比，并且与ESV变化率的提高直接相关。需要进行其他研究来探索健康个体中AV解偶联的功能后果，以与年龄相关的临床心血管疾病的出现，例如心力衰竭和保留的射血分数。 （alghatrif 2021） 以前的工作： D.我们发表了一篇论文，显示了ACE2水平与年龄相关的差异，这与老年CV合并症患者相关的19号与19号相关的死亡率有关（Alghatrif 2021） E.我们参加了一个研究项目，旨在使用包括CV的各种参数建立全球表型指标的衰老指标。 （Kuo 2020） F.使用台湾研究数据出版的出版物表明，波浪反射参数（但无动脉僵硬）与BP的较大可变性相关（HSU，2017年），BLSA的新发现表明，尿酸和脉搏波速度之间的纵向关联（Canepa，2016年）；在男人中观察到这种关联，但没有观察到女性。这些发现将光散发到先前观察到的随着衰老的动脉僵硬中的性别差异。撒丁岛研究的先前发现表明亚临床甲状腺功能减退症对内侧厚度没有影响，这是动脉衰老的表现（Delitala，2016） F. Sardinia研究的先前发现报道了白色外套的性别特异性和掩盖高血压对动脉结构和功能的影响（Scuteri 2016） 萨迪尼亚项目的先前发现表明，白色外套和掩盖高血压对动脉结构的影响有显着的性别差异（Scuteri 2016）。先前对动脉衰老的复杂性质的纵向洞察力。 巴尔的摩纵向衰老纵向研究（BLSA）的发现表明，脉搏波速度（PWV）的纵向增加，衰老在男性中更为明显（Alghatrif等，2013）。对萨迪尼亚项目的纵向数据的分析显示出相似的结果，但此外，它在促进年龄的男性中显示了PWV和SBP的纵向轨迹之间的有趣分离（Scuteri 2014）；这表明其他与年龄相关的过程（例如主动脉膨胀）可能会钝化壁变硬的作用并导致PWV和SBP的分离。在当前高血压报告（Alghatrif and Lakatta 2015）中发表的评论文章中，对这些发现以及其他报告进行了审查。 B.加速心血管衰老的遗传和环境基础 - 基因确定：撒丁岛研究的早期结果揭示了Col4a1基因的潜在作用（Tarasov 2009）和位于基因组沙漠地区的第二个遗传元素（Mitchell 2012），这在复制研究和基于复制伴侣的分析中已得到证实。正在进行研究PWV纵向变化的遗传决定因素。 - 环境决定因素：另一份使用Sardiania队列的报告没有显示亚临床甲状腺功能减退症对动脉僵硬的影响（Delitala 2015）。除了血压外，我们以前已经发现传统心血管危险因素在动脉僵硬发展中的作用最少（Alghatrif等，2013）。我们还发现，中央肥胖可能会引起PWV测量值（Canepa等，2014）。此外，我们发现维生素D调节了循环胰岛素样生长因子1与颈动脉内膜膜厚度的关联（Ameri等人，2014年）。我们还发现，骨矿物质密度在体大小和主动脉钙化之间的反比关系中起作用（Canepa et 2014）。使用BLSA和Sardinia项目的数据研究低度炎症在动脉僵硬中的作用的项目正在进行中。至于心脏funciton，BLSA的结果表明，内脏而不是皮下脂肪与更糟糕的心肌舒张功能障碍相关（M Canepa，Strait等，2013，此外，还有验证研究。在完成后续访问的最终阶段。 ii。先进的CV表型：为了进一步检查动脉衰老的复杂性质，我们启动了一项计划，该程序着重于对心血管生理信号的高级数学分析，包括压力，流量和几何信号，以得出参数，以推导参数，以更好地代表给定人员中CV的功能状态及其随着衰老的变化。我们招募了一位博士后研究员，接受了生物医学工程培训，并与国际专家建立了合作，以开发高级软件，以分析从BLSA和Sardinia参与者收集的CV特征。已经做出了巨大的努力来编译超声心动图，多普勒和应用传动系统的原始数据。生成的变量包括派生的中央血压，波反射参数，主动脉和颈动脉特性阻抗，颈动脉几何表型，颈动脉总数，收缩期和舒张期流量以及CV机械功率和效率。 初步数据表明，心脏效率随着衰老而下降，并且这种下降部分归因于主动脉阻抗增加和波反射的早期到达，但本身反射幅度本身。这些结果被接受在2016年美国心脏协会会议上进行演示。正在进行更全面的分析，并将编写手稿。 iii。动脉衰老对心脏几何和功能的影响： 对健康ABC研究的最新分析表明，动脉僵硬不是心力衰竭的独立危险因素（Pandey，2017年）

项目成果

Longitudinal perspective on the conundrum of central arterial stiffness, blood pressure, and aging.

• DOI: 10.1161/hypertensionaha.114.04127
• 发表时间: 2014-12
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: Scuteri A;Morrell CH;Orrù M;Strait JB;Tarasov KV;Ferreli LA;Loi F;Pilia MG;Delitala A;Spurgeon H;Najjar SS;AlGhatrif M;Lakatta EG
• 通讯作者: Lakatta EG

Power dynamics and health initiative design as determinants of peacebuilding: a case study of the Syrian conflict.

• DOI: 10.1136/bmjgh-2021-007745
• 发表时间: 2022-10
• 期刊: BMJ GLOBAL HEALTH
• 影响因子: 8.1
• 作者: AlGhatrif, Majd;Darwish, Mohammad;Alzoubi, Zedoun;Shawar, Yusra Ribhi
• 通讯作者: Shawar, Yusra Ribhi

IMT as a risk marker: the plot thickens.

IMT 作为风险标记：情节变得更加复杂。

• DOI: 10.1016/j.echo.2009.03.019
• 发表时间: 2009
• 期刊: Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography
• 作者: Najjar,SamerS

Bringing prevention in geriatrics: evidences from cardiovascular medicine supporting the new challenge.

• DOI: 10.1016/j.exger.2012.02.009
• 发表时间: 2013-01
• 期刊: Experimental gerontology
• 影响因子: 3.9
• 作者: Scuteri A;Lakatta EG
• 通讯作者: Lakatta EG

Central or peripheral systolic or pulse pressure: which best relates to target organs and future mortality?

• DOI: 10.1097/hjh.0b013e3283220ea4
• 发表时间: 2009-03
• 期刊: Journal of hypertension
• 影响因子: 4.9
• 作者: Wang KL;Cheng HM;Chuang SY;Spurgeon HA;Ting CT;Lakatta EG;Yin FC;Chou P;Chen CH
• 通讯作者: Chen CH