Abstract
Residual pulmonary vascular obstruction (RPVO) and chronic thromboembolic pulmonary hypertension (CTEPH) are both long-term complications of acute pulmonary embolism, but it is unknown whether RPVO can be predicted by variants of fibrinogen associated with CTEPH.
We used the Akaike information criterion to select the best predictive models for RPVO in two prospectively followed cohorts of acute pulmonary embolism patients, using as candidate variables the extent of the initial obstruction, clinical characteristics and fibrinogen-related data. We measured the selected models’ goodness of fit by analysis of deviance and compared models using the Chi-squared test.
RPVO occurred in 29 (28.4%) out of 102 subjects in the first cohort and 46 (25.3%) out of 182 subjects in the second. The best-fit predictive model derived in the first cohort (p=0.0002) and validated in the second cohort (p=0.0005) implicated fibrinogen Bβ-chain monosialylation in the development of RPVO. When the derivation procedure excluded clinical characteristics, fibrinogen Bβ-chain monosialylation remained a predictor of RPVO in the best-fit predictive model (p=0.00003). Excluding fibrinogen characteristics worsened the predictive model (p=0.03).
Fibrinogen Bβ-chain monosialylation, a common structural attribute of fibrin, helped predict RPVO after acute pulmonary embolism. Fibrin structure may contribute to the risk of developing RPVO.
Abstract
Fibrinogen helps predict residual pulmonary vascular obstruction after pulmonary embolism: results from the PROMPT study http://ow.ly/G7pY30m2HU6
Footnotes
This article has supplementary material available from erj.ersjournals.com
Author contributions: B. Planquette recruited patients, performed experiments and helped write the manuscript; O. Sanchez, J. Emmerich and G. Meyer helped design the study and contributed to the manuscript; J.J. Marsh, P.G. Chiles, R.E. Moore and G.B. Gugiu performed laboratory experiments and contributed to the manuscript; G. Le Gal planned analysis and contributed to the manuscript; T. Wolfson and A.C. Gamst performed statistical analyses and contributed to the manuscript. T.A. Morris is the study primary investigator, planned the study, performed experiments and contributed to the manuscript.
Conflict of interest: B. Planquette has nothing to disclose.
Conflict of interest: O. Sanchez reports grants, personal fees and non-financial support from Bayer, grants, personal fees and non-financial support from MSD, grants and non-financial support from Actelion, personal fees and non-financial support from BMS-Pfizer, grants from Daiichi Sankyo, personal fees from Chiesi and non-financial support from Boehringer Ingelheim, outside the submitted work.
Conflict of interest: J.J. Marsh has nothing to disclose.
Conflict of interest: P.G. Chiles has nothing to disclose.
Conflict of interest: J. Emmerich has nothing to disclose.
Conflict of interest: G. Le Gal has acted as a co-investigator in clinical trials for Portola Pharmaceuticals, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, LEO Pharma, Daiichi Sankyo and Bayer, and has received honoraria, not taken as salary from Bayer, Pfizer, LEO Pharma, Sanofi and bioMérieux, outside the submitted work.
Conflict of interest: G. Meyer reports grants from Bayer and non-financial support from Leo Pharma, BMS-Pfizer and Daiichi Sankyo, outside the submitted work.
Conflict of interest: T. Wolfson has nothing to disclose.
Conflict of interest: A.C. Gamst has nothing to disclose.
Conflict of interest: R.E. Moore has nothing to disclose.
Conflict of interest: G.B. Gugiu has nothing to disclose.
Conflict of interest: T.A. Morris reports grants from Bayer Pharmaceuticals, during the conduct of the study; personal fees for consulting from Bayer Pharmaceuticals, and personal fees for acting as an expert witness from Faegre Baker Daniels, outside the submitted work.
Support statement: The study was funded by research grants from Bayer Pharmaceuticals, Fonds de Recherche en Santé Respiratoire, France, R01HL095089 and through collaboration with the UCSD DNA Sequencing Facility (supported, in part, by grant 2 P30 CA023100-23 from the NIH) for performing DNA sequence analysis; and the City of Hope Mass Spectrometry and Proteomics Core Facility (supported, in part, by grant CA033572 from the NIH) for performing fibrinogen mass spectrometry analysis. The authors had full discretion over the study design, performance and creation of the manuscript. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received March 24, 2018.
- Accepted September 24, 2018.
- Copyright ©ERS 2018
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