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 在美国，心力衰竭的患病率正在上升，尤其是在黑人和老年人中。心力衰竭是一 疾病进行性分期，无症状的临床前心力衰竭发作通常很明显 几十年前就有症状的临床疾病。这为发现新的靶点提供了机会， 在临床前阶段进行干预，以预防或减缓进展至临床心力衰竭阶段。这 早期预防方法至关重要，因为一旦个人进入下一阶段， 不太可能报告中度至剧烈强度体力活动（MVPA）和心肺功能（CRF） 与终生临床心力衰竭风险降低独立相关;这种关系主要是 在中年或老年人中进行研究。光强度与体力活动（LPA）的关系尚不清楚 或久坐行为（SED）伴心力衰竭。这种对事件驱动端点的关注， 心力衰竭的进行性，并使该领域对发现新的靶点以改善更多的 可预测未来临床疾病的近端结局，包括N末端脑利钠肽前体 肽（NT-proBNP）、高敏心肌肌钙蛋白T（hscTnT）、峰值摄氧量（峰值VO 2）和心脏 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年内进展为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下降同时发生， 在中年的前10年，久坐时间（基于加速度计）的活动时间。鉴于这些 目前在CARDIA中没有生物标志物，因此这些暴露的影响尚未在本研究中进行测试。 或者在其他研究中。为了满足这一需求，我们提出了心脏活动和心力衰竭（ACT-HF） 研究，一个为期四年的辅助研究，以35年的核心考试（2020-21;队列年龄53-65岁）。参与者 将是所有参加核心考试、符合资格标准并同意参加（估计 n≥ 2，431）。为了补充35年的现存数据，CARDIA ACT-HF测量包括：（1）第三次加速度测量 充分表征中年的测量，（2）在CARDIA中NT-proBNP和hscTnT的首次测量（在20岁时， 30和35通过储存的血液样品），和（3）最终的最大分级运动试验（GXT）测试测量或 估计峰值VO 2。400米步行试验的有效性，作为最大GXT的可能替代， 未来的考试，将被测试。我们的目的是研究：（1）独立和同时的纵向关系， 20-a）报告的MVPA和B）CRF从成年早期到中年的年变化，以及15年变化 在中年收集的心力衰竭生物标志物;（2）独立和同时的纵向关系， 基于加速度计的a）MVPA，B）LPA，和c）中年期心力衰竭生物标志物的SED变化;和 (3)a）基于加速度计的MVPA、LPA和SED以及B）CRF与心力衰竭的双向关系 人生的各个阶段将在所有研究目标中检验这些关系与种族和性别的相互作用。

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.