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)

Heart failure is an emerging epidemic in the United States (U.S.); black men and women are particularly vulnerable. Without effective prevention strategies, across all levels of prevention, ≥8 million U.S. adults will be living with heart failure in 2030 with an associated financial burden of approximately $70 billion dollars. The prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing relative to heart failure with reduced ejection fraction. This is problematic given the underlying pathophysiology of HFpEF is multifactorial and refractory to current pharmacological therapies. While several studies and meta-analyses have demonstrated an inverse relation of physical activity (PA) and/or cardiorespiratory fitness (CRF) with incident, symptomatic heart failure, the majority of this evidence is based on reported estimates of moderate to vigorous intensity physical activity (MVPA) during leisure time, which provides an incomplete characterization of this complex behavioral phenotype. Further, this body of evidence is focused almost exclusively on later heart failure stages, with associated symptoms including exercise intolerance. Therefore, the window of opportunity to promote PA and reduce sedentary time (SED) to optimize cardiorespiratory fitness (CRF) and reduce initial risk or attenuate progression of heart failure to symptomatic stages is limited. To address these critical research gaps, we propose the Coronary Artery Risk Development in Young Adults (CARDIA) Activity and Heart Failure (ACT-HF) Study, a four-year ancillary study to the Year 35 CARDIA core exam (2020-21; cohort ages 53-65 years). The overall goals of CARDIA ACT-HF are to examine the relations of changes in CRF and reported PA from young adulthood to midlife and changes in accelerometer-based measures of PA and SED during midlife with heart failure risk and stage progression, or improvement. Participants will be all those who attend the Year 35 core exam who meet eligibility criteria and agree to participate (n≥2,431). CARDIA ACT-HF measures include: (1) accelerometry and (2) heart failure biomarkers: (a) N-terminal pro-brain natriuretic peptide (NT-proBNP), (b) high sensitivity cardiac Troponin T (hscTnT), and (c) maximal graded exercise test (GXT) with gas collection to provide an estimate of chronotropic incompetence via peak VO2.To accomplish these goals, we propose the following specific aims, to examine the: (1) relations of 35-year changes in CRF and PA beginning in young adulthood (18-30 years) with repeated heart failure biomarkers collected during midlife; (2) relations of 15-year changes in accelerometer-based PA and SED and heart failure biomarkers during midlife, and (3) bidirectional relations of accelerometer-based PA and SED with heart failure stages during midlife. Interaction by race and sex will be examined in all aims. CARDIA ACT-HF will be the first epidemiological investigation examining the contributions of young adult and midlife changes in fitness, PA and sedentary behaviors on heart failure risk and stage progression.