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Alberto Alonso-Fernández, MD, PhD; Mónica de la Peña, MD; Miguel Carrera, MD, PhD; Angela García Suquia, BPharm; Raquel Casitas, MD; Francisco García-Río, MD, PhD; Elizabet Martinez-Ceron, MD; Javier Pierola, PhD; Antonia Barceló, MD, PhD; Joan B. Soriano, MD, PhD; Carmen Fernández-Capitán, MD
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: See earlier cited article for author conflicts of interest.

aDepartment of Pneumology, University Hospital Son Espases, Palma de Mallorca, Spain

bDepartment of Clinical Analysis, University Hospital Son Espases, Palma de Mallorca, Spain

cResearch Unit, University Hospital Son Espases, Palma de Mallorca, Spain

dDepartment of Pneumology, University Hospital La Paz, IdiPAZ, Madrid, Spain

eDepartment of Internal Medicine, University Hospital La Paz, IdiPAZ, Madrid, Spain

fInstituto de Investigación Hospital Universitario de la Princesa (IISP), Universidad Autónoma de Madrid, Cátedra UAM-Linde, Madrid, Spain

gCIBER Enfermedades Respiratorias, Palma de Mallorca, Illes Balears, Spain

CORRESPONDENCE TO: Alberto Alonso-Fernández, MD, PhD, Servicio de Neumología, Hospital Universitario Son Espases, Carretera de Valldemossa 79, 07010 Palma de Mallorca, Spain


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2017;151(2):515-516. doi:10.1016/j.chest.2016.11.031
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We appreciate the interest in our article about the role of OSA as a risk factor for recurrent pulmonary embolism (PE) as well as the comments related to its interpretation and clinical implications.

In this paper, we reported for the first time that OSA is an independent risk factor for PE recurrence (the aim of the study). From our point of view, this finding has clinical relevance because of the high prevalence of OSA in patients with PE and the OSA-associated hypercoagulable state. Both the prevalence of an AHI > 5/h and an AHI > 10/h were significantly higher in patients with PE recurrence than in those who did not have a relapse (100% vs 70.3%; P = .002 and 84% vs 54%; P = .012, respectively). With respect to the AHI cutoff used for the analysis, as in many other studies, an AHI > 10 was chosen, since no patient with PE recurrence had an AHI < 5, which limited their use in the logistic regression and sensitivity analysis.

Twenty-five percent of patients (n = 30) were obese, and Tables 2 and 5 in our paper represent mean values ± SD. We did not find differences in BMI between patients with and those without PE recurrence, but we repeated the risk prediction analyses after excluding patients with obesity, and the addition of the new risk models significantly improved PE recurrence predictions. Previous studies that found obesity as a PE recurrence risk factor included thousands of patients,, and our study and the sample size were not calculated to answer this question. After adjusting for several confounding factors, including BMI, OSA remained as an independent risk factor for recurrent PE in the present study. It could be speculated that the risk of recurrent PE that is commonly attributed to obesity might be partially related to OSA, and it is also possible that OSA and obesity may additively or synergistically lead to upregulation of procoagulant activity that may increase the risk of PE recurrence.

We agree on the clinical importance of knowing the CPAP effect on the risk of recurrent PE, but as we stated, our study and the sample size were not designed to address this question, and a large randomized controlled trial is needed. As an exploratory objective of the study, we compared patients with OSA and adequate CPAP compliance with patients with OSA who did not receive CPAP or who had poor CPAP compliance. No significant risk differences between groups were found; however, when patients with OSA who were not receiving CPAP or those with poor CPAP compliance were compared with subjects without OSA or patients with OSA and adequate CPAP compliance, a higher risk of PE recurrence was found in the untreated patients with OSA. In addition, we found a tendency (although nonsignificant, as we acknowledged in the manuscript) for a higher PE recurrence rate among those patients with OSA and insufficient CPAP compliance compared with those using CPAP more than 4 h/night (17% vs 64%; P = .051).

We do not understand the choice of references 2 and 3 of Serin et al's letter, which are not related to the topic. Moreover, the last paragraph of their letter is confused and has some inaccuracies. Our risk model did not include BMI, FEV1/FVC, baseline arterial oxygen saturation (Sao2), or Epworth Sleepiness Scale. As shown in Table 3 of our paper, the PE recurrence risk model included as independent risk factors AHI > 10, nocturnal Sao2 (not baseline Sao2), D-dimer levels, and the percentage of total time study with Sao2 < 90% (CT90). The first two variables were clearly different between patients with and those without recurrence of PE (Table 2 in our paper). Recently, we reported that levels of D-dimer, a well-known PE recurrence risk factor, are increased in patients with OSA. Therefore, our univariate analysis probably failed to detect differences in the D-dimer levels between patients with and those without PE recurrence, but its role as a risk factor is evident when adjusted for AHI. Finally, we think the role of CT90 particularly remarkable in that it shows a negative relation with the risk of PE recurrence (Table 3 in our paper). Although the univariate analysis also found no difference in this variable between patients with and those without PE recurrence, this is probably due to its great dispersion. We interpret its incorporation into a multivariate model as an independent protective factor might to be due to its ability to discriminate between sustained intermittent hypoxia and continuous hypoxia. It might be speculated whether the incorporation of the CT90 into the risk model, along with that of AHI and mean nocturnal Sao2, constitutes indirect evidence of the contribution of intermittent hypoxia to the OSA-associated hypercoagulability state.

References

Alonso-Fernández A. .García Suquia A. .de la Peña M. .et al OSA is a risk factor for recurrent VTE. Chest. 2016;150:1291-1301 [PubMed]journal. [CrossRef] [PubMed]
 
Alonso-Fernández A. .de la Peña M. .Romero D. .et al Association between obstructive sleep apnea and pulmonary embolism. Mayo Clin Proc. 2013;88:579-587 [PubMed]journal. [CrossRef] [PubMed]
 
Heit J.A. .Mohr D.N. .Silverstein M.D. .et al Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med. 2000;160:761-768 [PubMed]journal. [CrossRef] [PubMed]
 
Eichinger S. .Hron G. .Bialonczyk C. .et al Overweight, obesity, and the risk of recurrent venous thromboembolism. Arch Intern Med. 2008;168:1678-1683 [PubMed]journal. [CrossRef] [PubMed]
 
García Suquia A. .Alonso-Fernández A. .de la Peña M. .et al High D-dimer levels after stopping anticoagulants in pulmonary embolism with sleep apnoea. Eur Respir J. 2015;46:1691-1700 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Tables

References

Alonso-Fernández A. .García Suquia A. .de la Peña M. .et al OSA is a risk factor for recurrent VTE. Chest. 2016;150:1291-1301 [PubMed]journal. [CrossRef] [PubMed]
 
Alonso-Fernández A. .de la Peña M. .Romero D. .et al Association between obstructive sleep apnea and pulmonary embolism. Mayo Clin Proc. 2013;88:579-587 [PubMed]journal. [CrossRef] [PubMed]
 
Heit J.A. .Mohr D.N. .Silverstein M.D. .et al Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med. 2000;160:761-768 [PubMed]journal. [CrossRef] [PubMed]
 
Eichinger S. .Hron G. .Bialonczyk C. .et al Overweight, obesity, and the risk of recurrent venous thromboembolism. Arch Intern Med. 2008;168:1678-1683 [PubMed]journal. [CrossRef] [PubMed]
 
García Suquia A. .Alonso-Fernández A. .de la Peña M. .et al High D-dimer levels after stopping anticoagulants in pulmonary embolism with sleep apnoea. Eur Respir J. 2015;46:1691-1700 [PubMed]journal. [CrossRef] [PubMed]
 
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