Late-life trajectories of cardiac function to define pathways of cardiac resilience

晚年心脏功能轨迹以确定心脏恢复力的途径

• 批准号: 10586407
• 负责人: Amil M Shah
• 金额: $ 179.56万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10586407
• 关键词: Acceleration; Activities of Daily Living; Address; Affect; Age; Age Years; Aging; Atherosclerosis Risk in Communities; Attention; Behavior; Biological; Cardiac; Cardiovascular Physiology; Cardiovascular system; Cell Aging; Communities; Data; Databases; Dementia; Development; Diet; Disease; Echocardiography; Education; Elderly; Exercise; Exposure to; Freedom; Functional disorder; Future; Genetic; Genetic Variation; Genomics; Goals; Health behavior; Heart failure; Impairment; Incidence; Income; Individual; Intervention; Intervention Studies; Left Ventricular Ejection Fraction; Measurement; Measures; Mediating; Modeling; Molecular; Molecular Target; Morbidity - disease rate; Myocardial dysfunction; National Heart, Lung, and Blood Institute; Neighborhoods; Neurocognitive; Outcome; Participant; Pathway interactions; Persons; Phenotype; Physical Function; Physical activity; Plasma; Prevalence; Prevention; Proteins; Proteomics; Race; Research; Research Proposals; Resources; Risk Behaviors; Risk Factors; Role; Sampling; Strategic vision; Subgroup; Symptoms; Visit; age related; aptamer; biracial; cardiovascular risk factor; circulating biomarkers; comorbidity; effective intervention; experience; frailty; functional outcomes; genome sequencing; genomic data; heart function; heart imaging; heart preservation; high risk; innovation; lifestyle factors; lung pressure; mild cognitive impairment; modifiable behavior; mortality; multidimensional data; novel; phenotypic data; preservation; prevent; protein biomarkers; public health priorities; resilience; senescence; social; social adversity; structural determinants; whole genome

Heart failure (HF) disproportionately affects older adults, who carry a high burden of cardiovascular risk factors and experience accelerated decline in cardiac function. Subsets of older adults do not experience progressive cardiac dysfunction, but the factors related to late-life cardiac resilience are not well defined. This is a critical barrier – and missed opportunity – to identify novel interventions and treatment targets to prevent HF. The objective in this application is to define the lifestyle factors, social drivers, and molecular pathways underlying cardiac resilience in very late life. The central hypothesis is that in addition to optimal risk factor control, salutary health behaviors (exercise, diet) and favorable structural factors (less social adversity) protect from age-related cellular senescence (assessable via plasma proteomics) and promote trajectories of preserved cardiac function in late life. Leveraging rich longitudinal phenotypic data – including echocardiography – of participants in the community-based Atherosclerosis Risk in Communities (ARIC) study, sequential echocardiography will be performed in ~2,175 participants attending the 12th study visit (age ~86±4), in addition to functional assessments and measurement of plasma proteomics. The resulting three serial echocardiograms over 12 years will be used to identify trajectories of change in cardiac function and to address the following aims: (1) Define late-life behaviors and factors associated with cardiac resilience; (2) Identify proteins and protein networks underlying cardiac resilience with particular attention to circulating markers of cellular senescence; and (3) Determine the association of cardiac resilience with preservation of physical and neurocognitive function and freedom from frailty. The contribution of the proposed research will be to define the impact of modifiable individual behaviors and structural factors on trajectories of cardiac function in very late life, establish the role of a novel and targetable biologic pathway, and quantify the relation of these trajectories to functional and neurocognitive outcomes highly relevant to older adults. This contribution will be significant in enabling the identification of persons at high risk of progressive LV dysfunction in very late life when traditional risk factors perform poorly, and in determining the importance of a promising and targetable biologic pathway to preserve cardiac function – essential steps to decrease HF-associated morbidity and mortality. This research proposal is fundamentally innovative in: (1) focusing on longitudinal cardiac imaging in very late-life (75 to 91 years of age) when data is sparse but CVD burden is high; (2) interrogating a novel biological pathway (cellular senescence) potentially impacting late-life cardiac, physical, and neurocognitive function using serial high throughput proteomics integrated with genomic data; and (3) using innovative analytic approaches to identify trajectories, including Bayesian nonparametric trajectory mixture modeling. The project outcomes are expected to provide a novel understanding of the shared biologic pathways underlying preservation of cardiovascular, physical, and neurocognitive function in late life.

心力衰竭 (HF) 对老年人的影响尤为严重，他们承受着较高的心血管风险 一些老年人不会经历心脏功能加速下降的情况。 进行性心脏功能障碍，但与晚年心脏恢复能力相关的因素尚不清楚。 是确定新的干预措施和治疗目标以预防疾病的一个关键障碍，也是错失的机会。 本应用的目标是定义生活方式因素、社会驱动因素和分子途径。 晚年潜在的心脏恢复能力的核心假设是，除了最佳风险因素之外。 控制、有益的健康行为（锻炼、饮食）和有利的结构性因素（较少的社会逆境）可以保护 避免与年龄相关的细胞衰老（可通过血浆蛋白质组学评估）并促进保存轨迹 利用丰富的纵向表型数据（包括超声心动图）评估晚年的心脏功能。 社区动脉粥样硬化风险 (ARIC) 研究的参与者，顺序 将在参加第 12 次研究访视的约 2,175 名参与者（年龄约 86±4 岁）中进行超声心动图检查， 另外还有血浆蛋白质组学的功能评估和测量由此产生的三个系列。 超过 12 年的超声心动图将用于识别心脏功能的变化轨迹并解决 目标如下： (1) 定义与心脏复原力相关的晚年行为和因素； 心脏恢复能力的蛋白质和蛋白质网络，特别关注循环标志物 (3) 确定心脏复原力与身体和功能保存的关系 所提出的研究的贡献将是定义神经认知功能和免于虚弱。 可改变的个人行为和结构因素对非常人的心功能轨迹的影响 晚年，建立一种新颖且可靶向的生物途径的作用，并量化这些途径的关系 与老年人高度相关的功能和神经认知结果的轨迹。 对于识别晚年进行性左室功能障碍高风险人群具有重要意义 当传统风险因素表现不佳时，以及在确定有前途和有针对性的风险因素的重要性时 保护心脏功能的生物途径——降低心力衰竭相关发病率的重要步骤 该研究提案在以下方面具有根本性创新：（1）关注纵向心脏成像。 在晚年（75 至 91 岁），数据稀疏但 CVD 负担很高（2）审阅小说； 生物途径（细胞衰老）可能影响晚年的心脏、身体和神经认知 使用与基因组数据集成的串行高通量蛋白质组学功能；以及（3）使用创新技术 识别轨迹的分析方法，包括贝叶斯非参数轨迹混合建模。 该项目的成果预计将为共享的生物途径提供新的理解 晚年心血管​​、身体和神经认知功能的潜在保护。

项目成果

Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction: The TOPCAT Trial.

射血分数保留的心力衰竭中的心房颤动：TOPCAT 试验。

• DOI: 10.1016/j.jchf.2018.05.005
• 发表时间: 2018-08-01
• 期刊: JACC. Heart failure
• 作者: M. Čikeš;B. Claggett;A. Shah;Akshay S. Desai;E. Lewis;Sanjiv J. Shah;I. An;E. O’Meara;J. Rouleau;N. Sweitzer;J. Fang;S. Saksena;B. Pitt;M. Pfeffer;S. Solomon
• 通讯作者: S. Solomon

Response by Pfeffer et al to Letter Regarding Article, "Heart Failure With Preserved Ejection Fraction in Perspective".

Pfeffer 等人对有关文章“透视保留射血分数的心力衰竭”的信件的回应。

• 发表时间: 2019-08-02
• 影响因子: 20.1
• 作者: Pfeffer, Marc A;Shah, Amil M;Borlaug, Barry A
• 通讯作者: Borlaug, Barry A

Reply: Different Phenotype Characterization in PARAGON-HF: An Unresolved Puzzle in Patients With HFpEF.

回复：PARAGON-HF 中的不同表型特征：HFpEF 患者中一个未解之谜。

• 发表时间: 2020-03-31
• 影响因子: 24
• 作者: Shah, Amil M;Cikes, Maja;Zile, Michael R;McMurray, John J V;Solomon, Scott D;PARAGON
• 通讯作者: PARAGON

Levels and Change in Galectin-3 and Association With Cardiovascular Events: The ARIC Study.

Galectin-3 的水平和变化以及与心血管事件的关联：ARIC 研究。

• 发表时间: 2020
• 影响因子: 5.4
• 作者: Aguilar, David;Sun, Caroline;Hoogeveen, Ron C;Nambi, Vijay;Selvin, Elizabeth;Matsushita, Kunihiro;Saeed, Anum;McEvoy, John W;Shah, Amil M;Solomon, Scott D;Boerwinkle, Eric;Ballantyne, Christie M
• 通讯作者: Ballantyne, Christie M

Association of Left Ventricular Systolic Function With Incident Heart Failure in Late Life.

左心室收缩功能与晚年心力衰竭事件的关联。

• 发表时间: 2021
• 影响因子: 24
• 作者: Reimer Jensen, Anne Marie;Zierath, Rani;Claggett, Brian;Skali, Hicham;Solomon, Scott D;Matsushita, Kunihiro;Konety, Suma;Butler, Kenneth;Kitzman, Dalane W;Biering;Shah, Amil M
• 通讯作者: Shah, Amil M