Background: Growth differentiation factor 15 (GDF-15) is a strong prognostic marker in sepsis and cardiovascular disease (CVD). The prognostic importance of GDF-15 in COVID-19 is unknown. Methods: Consecutive, hospitalized patients with laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and symptoms of COVID-19 were enrolled in the prospective, observational COVID MECH study. Biobank samples were collected at baseline, day 3 and day 9. The primary endpoint was admission to the intensive care unit or death during hospitalization, and the prognostic performance of baseline and serial GDF-15 concentrations were compared with that of established infectious disease and cardiovascular biomarkers. Results: Of the 123 patients enrolled, 35 (28%) reached the primary endpoint; these patients were older, more often had diabetes mellitus, had lower oxygen saturations and higher National Early Warning Score on baseline. Baseline GDF-15 concentrations were elevated (>95th percentile in age-stratified healthy individuals) in 97 (79%), and higher concentrations were associated with detectable SARS-CoV-2 viremia and hypoxemia (both p<0.001). Patients reaching the primary endpoint had higher concentrations of GDF-15 (median 4225 [IQR 3197-5972] pg/mL vs 2187 [1344-3620] pg/mL, p<0.001). The C-statistic value was 0.78 (95% confidence interval 0.70-0.86). The association between GDF-15 and outcome persisted after adjusting for age, sex, race, body mass index, estimated glomerular filtration rate and previous myocardial infarction, heart failure or atrial fibrillation (p<0.001), and was superior and incremental to interleukin-6, C-reactive protein, procalcitonin, ferritin, D-dimer, cardiac troponin T and N-terminal pro-B-type natriuretic peptide. Increase in GDF-15 from baseline to day 3 was also greater in patients reaching the primary endpoint (median 1208 [IQR 0-4305] pg/mL versus -86 [IQR -322-491] pg/mL, p<0.001). Conclusions: GDF-15 is elevated in the majority of patients hospitalized with COVID-19, and higher concentrations are associated with SARS-CoV-2 viremia, hypoxemia and worse outcome. The prognostic importance of GDF-15 was additional and superior to established cardiovascular and inflammatory biomarkers.
Whether reversible ischaemia in patients referred for exercise stress testing and MPI (myocardial perfusion imaging) is associated with changes in circulating cTn (cardiac troponin) levels is controversial. We measured cTnT with a sensitive assay before, immediately after peak exercise and 1.5 and 4.5 h after exercise stress testing in 198 patients referred for MPI. In total, 19 patients were classified as having reversible myocardial ischaemia. cTnT levels were significantly higher in patients with reversible myocardial ischaemia on MPI at baseline, at peak exercise and after 1.5 h, but not at 4.5 h post-exercise. In patients with reversible ischaemia on MPI, cTnT levels did not change significantly after exercise stress testing [11.1 (5.2–14.9) ng/l at baseline compared with 10.5 (7.2–16.3) ng/l at 4.5 h post-exercise, P=0.27; values are medians (interquartile range)]. Conversely, cTnT levels increased significantly during testing in patients without reversible myocardial ischaemia [5.4 (3.0–9.0) ng/l at baseline compared with 7.5 (4.6–12.4) ng/l, P<0.001]. In conclusion, baseline cTnT levels are higher in patients with MPI evidence of reversible myocardial ischaemia than those without reversible ischaemia. However, although cTnT levels increase during exercise stress testing in patients without evidence of reversible ischaemia, this response appears to be blunted in patients with evidence of reversible ischaemia. Mechanisms other than reversible myocardial ischaemia may play a role for acute exercise-induced increases in circulating cTnT levels.
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