High D-dimer levels were associated with lung parenchymal abnormalities on computed tomography (CT) scans, higher serum matrix metalloproteinase-7 (MMP-7) concentrations, and a more rapid decline in forced vital capacity (FVC) in a cohort of individuals from the longitudinal Multi-Ethnic Study of Atherosclerosis (MESA), according to results of an analysis published in Annals of the American Thoracic Society.
Researchers examined the hypothesis that higher circulating levels of D-dimer are linked to a greater burden of lung abnormalities detected on CT scans by collecting data from MESA, an ongoing study among community-dwelling adults without clinical cardiovascular disease at the time of study recruitment (N=6184; exam 1: between 2000 and 2002). The associations between baseline D-dimer levels and high attenuation areas (HAAs) from exam 1 (all participants) were evaluated. Interstitial lung abnormalities from exam 5 CT scans (between 2010 and 2012; n=2227), and serum MMP-7 levels and surfactant protein-A (SP-A) from exam 1 (n=1098), were also assessed. Longitudinal changes in FVC from exams 3 to 6 were examined (between 2004 and 2018; n=3562).
Study participants were between 45 and 84 years of age, with a mean age of 62±10 years. Mean D-dimer level was 0.35±0.69 µg/mL. Fasting blood samples were obtained at exam 1, processed, and stored. Serum matrix metalloproteinase-7 and SP-A circulating biomarkers were measured from exam 1 serum samples. Full-lung CT scans were performed in exam 5.
For every 10% increase in D-dimer level, an increase in HAA percent of 0.27 (95% CI, 0.08-0.47) was reported, following adjustment for covariates. The relationships were stronger among participants older than 65 years of age (P values for interaction <.001).
Overall, the absolute rate of FVC decline was -1.04 mL/y (95% CI, -1.10 to -0.99) in participants with D-dimer levels and FVC measurements available. After adjustment for covariates and interleukin-6 levels, higher baseline D-dimer level was linked to a more rapid decline in FVC over time. For every 10% increase in D-dimer, an absolute change of -0.03 mL (95% CI, -0.06 to -0.003) and a relative decline of -2.97% (95% CI, -5.33 to -0.35) per year were observed. Higher D-dimer levels were linked to higher serum MMP-7 levels and a more rapid decline in FVC.
A major limitation of the current study is the fact that although baseline D-dimer levels were associated with a longitudinal decrease in FVC, the remaining associations were cross-sectional, thus limiting temporal associations.
The researchers concluded that additional longitudinal studies are warranted, with lung sampling of the parenchymal abnormalities, along with examination of coagulopathy markers and histopathologic features of thrombin and fibrin deposition, included in these analyses.
Kim JS, Anderson MR, Bernstein EJ, et al. Associations of D-dimer with CT lung abnormalities, serum biomarkers of lung injury, and forced vital capacity: MESA Lung Study. Ann Am Thorac Soc. Published online April 16, 2021. doi:10.1513/AnnalsATS.202012-1557OC