Association of 71 cardiovascular disease-related plasma proteins with pulmonary function in the community

RATIONALE: It has been speculated that shared mechanisms underlie respiratory and cardiovascular diseases (CVD) including systemic inflammation or mutual risk factors. In this context, we sought to examine the associations of CVD-related plasma proteins with lung function as measured by spirometry in a large community-based cohort of adults. METHODS: The study included 5777 Framingham Heart Study participants who had spirometry and measurement of 71 CVD-related plasma proteins. The association of plasma proteins with lung function was assessed cross-sectionally and longitudinally using models accounting for familial correlations. Linear mixed models were used for the following measurements: FEV(1%predicted), FVC(%predicted), and FEV(1)/FVC ratio with secondary analyses examining obstructive and restrictive physiology at baseline and their new onset during follow up. MEASUREMENTS AND MAIN RESULTS: Among the 71 CVD-related plasma proteins, 13 proteins were associated in cross-sectional analyses with FEV(1%predicted), 17 proteins were associated with FVC(%predicted), and 1 protein was associated with FEV(1)/FVC. The proteins with the greatest inverse relations to FEV(1%predicted) and FVC(%predicted) included leptin, adrenomedullin, and plasminogen activator inhibitor-1; in contrast there were three proteins with positive relations to FEV(1%predicted) and FVC(%predicted) including insulin growth factor binding protein 2, tetranectin, and soluble receptor for advanced glycation end products. In longitudinal analyses, three proteins were associated with longitudinal change in FEV(1) (ΔFEV(1)) and four with ΔFVC; no proteins were associated with ΔFEV(1)/FVC. CONCLUSION: Our findings highlight CVD-related plasma proteins that are associated with lung function including markers of inflammation, adiposity, and fibrosis, representing proteins that may contribute both to respiratory and CVD risk.