Associations of D-dimer with CT Lung Abnormalities, Serum Biomarkers of Lung Injury, and Forced Vital Capacity: MESA Lung Study.

Overview

abstract

RATIONALE: The coagulation cascade may play a role in the pathogenesis of interstitial lung disease through increased production of thrombin and fibrin deposition. Whether circulating coagulation cascade factors are linked to lung inflammation and scarring among community-dwelling adults is unknown. OBJECTIVE: To test the hypothesis that higher baseline D-dimer levels are associated with markers of early lung injury and scarring. METHODS: Using the Multi-Ethnic Study of Atherosclerosis cohort (n=6,814), we examined associations of baseline D-dimer levels with high attenuation areas (HAA) from Exam 1 (2000-2002, n=6,184) and interstitial lung abnormalities (ILA) from Exam 5 computed tomography (CT) scans (2010-2012, n=2,227), and serum matrix metalloproteinase-7 (MMP-7) and surfactant protein-A (SP-A) from Exam 1 (n=1,098). We examined longitudinal change in forced vital capacity (FVC) from Exams 3-6 (2004-2018, n=3,562). We used linear, logistic regression, and linear mixed models to examine associations and adjust for potential confounders. RESULTS: The mean (SD) age of the cohort was 62 (10) years and D-dimer level was 0.35 (0.69) ug/mL. For every 10% increase in D-dimer level, there was an increase in HAA percent of 0.27 (95% CI 0.08 to 0.47) after adjustment for covariates. Associations were stronger among those older than 65 years (p-values for interaction<0.001). A 10% increase in D-dimer level was associated with an odds ratio of 1.05 for ILA (95% CI 0.99 to 1.11). Higher D-dimer levels were associated with higher serum MMP-7 and a faster decline in FVC. D-dimer was not associated with SP-A. CONCLUSIONS: Higher D-dimer levels were associated with a greater burden of lung parenchymal abnormalities detected on CT scan, MMP-7, and FVC decline among community-dwelling adults.