Abstract
Background: Heart failure is associated with a restrictive spirometry pattern, but limited data is available on the relation of subclinical measures of pulmonary function to cardiac function. We sought to explore such associations in a population-based cohort study as well as metabolic factors commonly associated with such measures. Methods: Participants of the population-based Swedish cohort study SCAPIS-Malmö (age 50-64) underwent spirometry (n=6251), of which random subsets also underwent echocardiograpy (n=1885) and untargeted plasma metabolite profiling (n=3,986). The association of spirometric (FEV1, FVC, DLCO) and echocardiographic parameters (E/E', stroke volume [SV], systolic pulmonary arterial pressure [sPAP]) were examined using multivariable-adjusted regression models and cubic spline functions.Metabolites were tested for association with spirometric and echocardiographic parameters with adjustment for age, sex, bmi, smoking, eGFR, diabetes, hypertension, COPD, asthma, and heart failure. Results: After adjustment for smoking and other established risk factors, lower FEV1, FVC and DLCO remained associated with higher E/E', sPAP, and lower SV (p<0.001). Spline analyses were consistent with linear effects. Profiling of 1318 metabolites identified associations with lower FEV1, FVC, DLCO and higher E/E' for lower levels of 6 correlated lipid molecules including plasmalogens, lysophospholipids and a phosphatidylcholine, all of which also correlated with the main constituent of pulmonary surfactant (dipalmitoylphosphatidylcholine), and with higher levels of an amino acid and its deaminated product. Lower levels of bilirubin were associated with lower FEV1, FVC, DLCO, and lower SV. Discussion: In this contemporary, middle-aged cohort with low prevalence of manifest cardiac or pulmonary disease we observed associations between lower lung volumes and CO diffusion capacity with restrictive cardiac filling. Furthermore, our findings nominate metabolic factors that associate with both cardiac and pulmonary function, suggestive of shared pathophysiological processes.
Published Version
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