Heart failure (HF) and chronic obstructive pulmonary disease (COPD) often co-exist and are associated with increased risk of morbidity and mortality. COPD is the most common non-cardiovascular comorbidity in patients with HF, ranging from 29% to 38% in each subtype of HF (reduced or preserved ejection fraction). Mechanisms underlying comorbid cardiopulmonary disease include shared risk factor burden (e.g. tobacco exposure), fibrotic injury (e.g. galectin-3, matrix metalloproteinases 7 and 9 [MMP-7,9], and plasminogen activator inhibitor-1), and mechanical interdependence between the heart, lung, and pulmonary vasculature. Emphysematous destruction of the lung in COPD has been traditionally associated with right-sided ventricular dysfunction or cor pulmonale (right ventricular enlargement and pulmonary hypertension), but emerging evidence suggests counterintuitive decreases in left ventricular (LV) size in those with COPD that is associated with reduced exercise capacity and mortality. While this finding of a shrinking heart has been attributed, in part, to impaired LV filling and compressive effects of the lung, the temporal relationship, underlying mechanisms, and flow dynamics are not well-understood. Further, whether early, but heterogeneous responses to injury (due to a variety of causes) in the lung may differentially influence cardiac structure and function is unknown. Therefore, there is a critical need to characterize heart-lung interactions across the life course to inform targeted and intensive prevention strategies to improve outcomes. Without such information, mitigating the growing burden of HF will likely remain limited. While symptomatic HF and COPD typically occur in the elderly, many younger adults have asymptomatic structural or functional impairments in the heart and lung. Longitudinal data from the Coronary Artery Risk Development in Young Adults (CARDIA) study demonstrate age-related decline in cardiac function and pathologic remodeling from ages 25 to 55 years, with higher prevalence of Stage B HF in Black compared with White adults. Separately, trajectories of lung function alone (as measured by forced expiratory volume in one second or FEV1) in CARDIA were associated with risk of future HF. However, data are sparse on the timing and sequence of decline in heart and lung health from young adulthood to middle-age, and related race-sex differences. To address these significant knowledge gaps, the overall goals of this proposal are to examine the concurrent evolution, interdependence, and mechanisms of heart and lung structure changes from young adulthood to midlife with HF risk. These goals will be accomplished by conducting a four-year ancillary study in CARDIA and leverages repeated phenotypic data spanning 35 years in a biracial cohort. Ancillary study measures will add (1) quantitative assessment of the epicardial volume (myocardium and chamber) of the right and left ventricle (RV/LV) and pulmonary vasculature size and density from available noncardiac gated, unenhanced chest CT scans and (2) biomarkers of fibrosis and inflammation (galectin-3, MMP-7,9, and PAI-1) in all participants who attend Y35 (N=XXXX, 2021-22) and (3) deep phenotyping with 4-dimensional cardiac magnetic resonance imaging (MRI) in a subset of the Chicago Field Center participants (N=200, 2022-23). All aims will explore interactions by race and sex. Specifically, we propose to use multidimensional Bayesian trajectory modeling to complete the following Specific Aims: Aim 1 (Prevalence of LV cardiac remodeling across pulmonary trajectori
|Effective start/end date
|9/1/21 → 5/31/26
- National Heart, Lung, and Blood Institute (5R01HL159250-02)
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.