Plasma levels of mitochondrial and nuclear DNA in patients with massive pulmonary embolism in the emergency department: A prospective cohort study
Entity
UAM. Departamento de Farmacología; UAM. Departamento de Medicina; UAM. Departamento de PediatríaPublisher
BioMed CentralDate
2013-05-24Citation
10.1186/cc12735
Critical Care 17 (2013): 90
ISSN
1364-8535DOI
10.1186/cc12735Funded by
This work was supported partially by grants from Plan Nacional I+D+I (SAF 2008-05347 and SAF2011-23575) and from Fundación Mutua Madrileña de Investigación Biomédica (2008 and 2011) to Francisco Arnalich and Carmen MontielEditor's Version
http://ccforum.com/content/17/3/R90Subjects
cell-free plasma DNA; heart-type fatty acid-binding protein; hospital mortality; massive pulmonary embolism; plasma mitochondrial DNA; plasma nuclear DNA; prognosis; MedicinaRights
© 2013 Arnalich et al.; licensee BioMed Central Ltd.Abstract
Introduction: Cell-free plasma mitochondrial DNA (mt-DNA) and nuclear DNA (n-DNA) are biomarkers with
prognostic utility in conditions associated with a high rate of cell death. This exploratory study aimed to determine
the plasma levels of both nucleic acids in patients with massive and submassive pulmonary embolism (PE) and to
compare them with other biomarkers, such as heart-type fatty acid-binding protein (H-FABP) and troponin I (Tn-I)
Methods: This was a prospective observational study of 37 consecutive patients with massive PE, 37 patients with
submassive PE, and 37 healthy subjects. Quantifications of plasma mt-DNA and n-DNA with real-time quantitative
polymerase chain reaction (PCR), and plasma H-FABP and Tn-I by commercial assays, were done on blood samples
drawn within 4 hours after presentation at the emergency department.
Results: Plasma mt-DNA and n-DNA concentrations were much higher in patients with massive PE (median, 2,970
GE/ml; interquartile range (IQR), 1,050 to 5,485; and 3,325 GE/ml, IQR: 1,080 to 5,790, respectively) than in patients
with submassive PE (870 GE/ml and 1,245 GE/ml, respectively; P < 0.01) or controls (185 GE/ml and 520 GE/ml,
respectively). Eighteen patients with massive PE died of a PE-related cause by day 15 of observation. Plasma mt-
DNA and n-DNA values were 2.3-fold and 1.9-fold higher in the subgroup of nonsurviving patients than in
survivors. H-FABP and Tn-I values were also higher in patients with massive PE who died (7.3 ng/ml and 0.023 ng/ml,
respectively) than in those who survived (6.4 ng/ml, and 0.016 ng/ml, respectively). By receiver operating curve (ROC)
analysis, the best cutoff values for predicting 15-day mortality were 3,380 GE/ml for mt-DNA, 6.8 ng/ml for H-FABP,
3,625 GE/ml for n-DNA, and 0.020 ng/ml for Tn-I, based on the calculated areas under the curve (AUCs) of 0.89
(95% confidence interval (CI), 0.78 to 0.99), 0.76 (95% CI, 0.69 to 093), 0.73 (95% CI, 0.58 to 0.91), and 0.59 (95% CI,
0.41 to 0.79), respectively. By stepwise logistic regression, a plasma mt-DNA concentration greater than 3,380 GE/ml
(adjusted odds ratio (OR), 8.22; 95% CI, 1.72 to 39.18; P < 0.001) and a plasma value of H-FBAP >6.8 ng/ml (OR, 5.36;
95% CI, 1.06 to 27.08; P < 0.01) were the only independent predictors of mortality.
Conclusions: mt-DNA and H-FBAP might be promising markers for predicting 15-day mortality in massive PE, with
mt-DNA having better prognostic accuracy.
Files in this item
Google Scholar:Arnalich Fernández, Francisco
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Maldifassi, Maria Constanza
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Ciria, Enrique
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Codoceo, Rosa
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Renart, Jaime
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Fernández Capitán, María del Carmen
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Herruzo Cabrera, Rafael
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García Rio, Francisco
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López-Collazo, Eduardo
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Montiel López, Carmen
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