Young Adult and Midlife Transitions in Physical Activity and Sedentary Behavior with Heart Failure Risk and Progression: Coronary Artery Risk Development in Young Adults (CARDIA)

摘要 心力衰竭在美国的患病率正在上升，特别是在黑人和老年人中。心力衰竭是一种 进展性疾病按分期定义，无症状、临床前心力衰竭的发病通常很明显。 比有症状的临床疾病早了几十年。这为发现新的目标提供了机会 在临床前阶段进行干预，以防止或减缓进展到临床心力衰竭阶段。这 早期预防方法是至关重要的，因为一旦个人进入下一阶段，回归是 不太可能。据报道，中等到剧烈的体力活动(MVPA)和心肺功能(CRF) 独立地与降低终生、临床心力衰竭的风险相关；这种关系主要是 在中年或老年人中学习。关于光强度和体力活动(Lpa)之间的关系，我们一无所知。 或久坐行为(SED)并心力衰竭。这种对事件驱动的端点的关注降低了 心力衰竭的渐进性特征，并使该领域对发现新的靶点以改善更多 预测未来临床疾病的近期结果，包括N末端前脑利钠药 多肽(NT-proBNP)、高敏心肌肌钙蛋白T(HscTnT)、峰值摄氧量(峰值VO2)与心脏 故障阶段分类。来自CARDIA的证据表明临床前心脏病的患病率增加 心力衰竭，并在25年内进展到更严重的心力衰竭阶段，定义了青年到中年。 这与这25年来报告的MVPA和CRF的下降同步发生，并 在中年的头10年，久坐时间的活动时间(基于加速计)。考虑到这些 生物标志物目前在CARDIA中不可用，这些暴露的影响尚未在 队列，或在其他研究中。为了解决这一需求，我们提出了CARDIA活动和心力衰竭(ACT-HF) 研究，35年核心考试(2020-21年；年龄53-65岁)为期四年的辅助研究。参与者 将是所有参加核心考试、符合资格标准并同意参加的人(估计 N≥2,431)。为了补充35年来的现有数据，CARDIA ACT-HF测量包括：(1)第三加速度计 充分描述中年特征的措施，(2)CARDIA中NT-proBNP和hscTnT的第一次测量(20岁， 30和35通过存储的血液样本)，以及(3)最终最大分级运动试验(GXT)测试 估计的最大摄氧量。400米步行试验作为最大GXT的替代试验的有效性 未来的考试，将会被测试。我们的目标是研究：(1)独立的和同时的纵向关系 A)报告的MVPA和b)CRF从成年早期到中年的20年变化，其中 在中年期间收集的心力衰竭生物标志物；(2)独立和同时的纵向关系 基于加速计的a)MVPA、b)LPA和c)SED随中年心力衰竭生物标志物的变化；以及 (3)基于加速度计的MVPA、LPA和SED的双向关系以及b)CRF与心力衰竭的关系 跨越中年的各个阶段。种族和性别之间的相互作用将在所有研究目标中得到检验。

ABSTRACT Heart failure prevalence is increasing in the U.S., particularly among blacks and older adults. Heart failure is a progressive disease defined by stages, and onset of asymptomatic, preclinical heart failure is often evident decades before symptomatic, clinical disease. This provides an opportunity to discover novel targets for intervention during preclinical stages to prevent or attenuate progression to clinical heart failure stages. This early prevention approach is critical since, once an individual advances to the next stage, regression is unlikely. Reported moderate to vigorous intensity physical activity (MVPA) and cardiorespiratory fitness (CRF) are independently related to a reduced risk of lifetime, clinical heart failure; a relation that has been primarily studied in midlife or older adults. Nothing is known about the relations of light intensity physical activity (LPA) or sedentary behaviors (SED) with heart failure. This focus on event-driven endpoints discounts the progressive nature of heart failure and biases the field against discovery of novel targets for improving more proximal outcomes that are predictive of future clinical disease, including N-terminal pro-brain natriuretic peptide (NT-proBNP), high sensitivity cardiac Troponin T (hscTnT), peak oxygen uptake (peak VO2), and heart failure stage classification. Evidence from CARDIA demonstrates an increased prevalence of preclinical heart failure, and progression to more severe heart failure stages over 25-years defining young adulthood to midlife. This has occurred in parallel with declines in reported MVPA and CRF over these 25-years, and replacement of active time for sedentary time (based on accelerometry) during the first 10-years of midlife. Given that these biomarkers are not currently available in CARDIA, the impacts of these exposures have not been tested in this cohort, or in other studies. To address this need, we propose the CARDIA Activity and Heart Failure (ACT-HF) Study, a four-year ancillary study to the Year 35 core exam (2020-21; cohort ages 53-65 years). Participants will be all those who attend the core exam, who meet eligibility criteria, and agree to participate (estimated n≥2,431). To complement 35-years of extant data, CARDIA ACT-HF measures include: (1) third accelerometry measures to fully characterize midlife, (2) first measures of NT-proBNP and hscTnT in CARDIA (at Years 20, 30 & 35 via stored blood samples), and (3) a final maximal graded exercise test (GXT) test for measured or estimated peak VO2. The validity of the 400-meter walk test, as a possible replacement for the maximal GXT in future exams, will be tested. We aim to examine the: (1) independent and simultaneous longitudinal relations of 20-year changes in a) reported MVPA and b) CRF from early adulthood to midlife with 15-year changes in heart failure biomarkers collected across midlife; (2) independent and simultaneous longitudinal relations of accelerometer-based a) MVPA, b) LPA, and c) SED changes with heart failure biomarkers across midlife; and (3) bidirectional relations of a) accelerometer-based MVPA, LPA, and SED and b) CRF with heart failure stages across midlife. Interactions of these relations by race and sex will be tested in all study aims.