International Journal of Cardiology 184 (2015) 481–482
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Is obstructive sleep apnea associated with the risk of ischemic stroke in patients with atrial fibrillation? Filip M. Szymanski ⁎, Anna E. Platek, Krzysztof J. Filipiak 1st Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
a r t i c l e
i n f o
Article history: Received 13 January 2015 Accepted 24 February 2015 Available online 26 February 2015 Keywords: Atrial fibrillation Obstructive sleep apnea CHA2DS2-VASc CHADS2 Thromboembolic risk
Atrial fibrillation (AF) is one of the most important preventable causes of ischemic stroke. Current guidelines recommend assessing the thromboembolic risk by either CHADS2 or CHA2DS2-VASc scores [1]. Unfortunately, both scores base only on age and previously diagnosed comorbidities, and tend to omit many important aspects that strongly influence patients' risk and prognosis. Factors such as left atrial morphology and function or chronic kidney disease were previously shown to be associated with higher risk of stroke and influence the necessity of anticoagulation in atrial fibrillation patients [2,3]. Another factor which may bring additional value to the assessment of thromboembolic risk in AF patients is the presence of obstructive sleep apnea (OSA). OSA is one of the types of sleep disordered breathing most prevalent in the general population. In numerous, large, prospective studies OSA was shown to be associated with increased risk of stroke and death in the general population [4]. Thromboembolic risk associated with OSA is a cause of deep vein thrombosis, pulmonary embolism and in-stent thrombosis [5,6]. The concept of an increased thromboembolic risk associated with co-existence of OSA and AF, which exceeds the risk calculated by CHADS2 or CHA2DS2-VASc scores is not new. Yazdan-Ashoori and Baranchuk even proposed to include OSA in those schemes to increase their predictive value [7]. Nevertheless, there is still not enough data in the literature supporting this concept. Therefore, the more willingly the readers will probably welcome
⁎ Corresponding author at: 1st Department of Cardiology, Medical University of Warsaw, 1A Banacha Street, PL02-097 Warsaw, Poland. E-mail address: fi[email protected] (F.M. Szymanski).
http://dx.doi.org/10.1016/j.ijcard.2015.02.091 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
the work by Chang et al. published in the recent issue of the International Journal of Cardiology [8]. We would like to congratulate the authors of the study, which could provide interesting, new data on the topic. Unfortunately, there is a concern that some parts of the study methodology are not properly chosen, and therefore cause the main study finding to be to far gone. The main conclusion of the study is that adding OSA to CHA2DS2VASc does not improve its predictive value in AF patients. It was not properly proven. First of all the study did not include (all) OSA patients, but patients with “severe OSA requiring CPAP (continuous positive airway pressure) treatment” identified basing on a registry. It is a strictly specified subgroup. In order to receive CPAP treatment, OSA first needs to be properly diagnosed, which given the fact that the disease is largely underdiagnosed, will cause potential bias. Second of all, not every OSA patient requires CPAP treatment, and even those who do, do not always tolerate and adhere to the treatment. This is proven by the fact that only 0.8% of the AF patients enrolled into the study were considered as “having OSA”, which is even much less than in the general population. We have previously shown that in AF patients qualified for ablation (which account for a relatively young and healthy subgroup of AF population) the prevalence of all OSA is 45.49% [9]. Our study protocol required sleep-study screening in consecutive patients, regardless of their symptoms and therefore showed reliable data on the sleep disordered breathing prevalence. One would expect for the OSA prevalence in unselected AF patients to be at least as high or even higher. Moreover, few additional factors influence the findings. The major concern is that, the treatment with CPAP ameliorates all impact of OSA on stroke risk. It has been well documented that CPAP reverses hemodynamic, vascular, metabolic, and thrombotic changes caused by OSA. Data in this kind of study can be valid only if CPAP-naïve patients are considered. Also, a relatively small sample size (133 OSA patients) might be responsible for low statistical power. A small, but significant increase in some stroke risk factors in OSA patients was found; thus there is confounding for which the small sample size does not permit full adjustment. Also 1 point added a priori (without any statistical calculations) to the CHA2DS2-VASc score may be too much or too little. Maybe OSA would account to only 0.5 points, or contrary - event to 2 or 3 points, basing on the added risk? Thus, the improper selection of patients leads to the finding that OSA does not add to the predictive value of CHA2DS2-VASc cannot be predictive for the whole AF population, and in this context, their negative finding is less worthy.
482
F.M. Szymanski et al. / International Journal of Cardiology 184 (2015) 481–482
We still have to wait for a study, which would show if OSA is truly a factor that can add predictive value for the CHA2DS2-VASc or CHADS2 score. Nevertheless, there is already data that show that OSA patients have higher CHADS2 and CHA2DS2-VASc scores than patients without sleep disordered breathing. Also, mean CHADS2 and CHA2DS2-VASc scores rise with OSA severity and the differences in the stroke risk are significant even across different age strata, and the trend for point values in CHADS2 and CHA2DS2-VASc scores rises along with OSA severity according to the apnea–hypopnea index [10]. All these arguments show that AF patients with OSA do have higher thromboembolic risk, but whether it will add additional value to the stroke prediction models remains a field for further research. Conflict of interest
[3]
[4]
[5]
[6]
[7] [8]
The authors report no relationships that could be construed as a conflict of interest. References [1] A.J. Camm, G.Y. Lip, R. De Caterina, I. Savelieva, D. Atar, S.H. Hohnloser, G. Hindricks, P. Kirchhof, ESC Committee for Practice Guidelines (CPG), 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association, Eur. Heart J. 33 (2012) (2010) 2719–2747. [2] A. Hrynkiewicz-Szymanska, M. Dluzniewski, A.E. Platek, F.M. Szymanski, J. SyskaSuminska, A. Klos-Szadryn, M. Glinka, M. Strojek, A. Kuciej, M. Tomaszewska-
[9]
[10]
Kiecana, Association of the CHADS2 and CHA 2DS 2-VASc scores with left atrial enlargement: a prospective cohort study of unselected atrial fibrillation patients, J. Thromb. Thrombolysis (2014) http://dx.doi.org/10.1007/s11239-014-1154-6 (Ahead of print). A.N. Bonde, G.Y. Lip, A.L. Kamper, P.R. Hansen, M. Lamberts, K. Hommel, M.L. Hansen, G.H. Gislason, C. Torp-Pedersen, J.B. Olesen, Net clinical benefit of antithrombotic therapy in patients with atrial fibrillation and chronic kidney disease: a nationwide observational cohort study, J. Am. Coll. Cardiol. 64 (2014) 2471–2482. H.K. Yaggi, J. Concato, W.N. Kernan, J.H. Lichtman, L.M. Brass, V. Mohsenin, Obstructive sleep apnea as a risk factor for stroke and death, N. Engl. J. Med. 353 (2005) 2034–2041. Y.H. Peng, W.C. Liao, W.S. Chung, C.H. Muo, C.C. Chu, C.J. Liu, C.H. Kao, Association between obstructive sleep apnea and deep vein thrombosis/pulmonary embolism: a population-based retrospective cohort study, Thromb. Res. 134 (2014) 340–345. A. Hrynkiewicz-Szymanska, F.M. Szymanski, K.J. Filipiak, M. Grabowski, A. Dąbrowska-Kugacka, G. Karpinski, G. Opolski, Can obstructive sleep apnea be a cause of in-stent thrombosis? Sleep Breath. 15 (2011) 607–609. P. Yazdan-Ashoori, A. Baranchuk, Obstructive sleep apnea may increase the risk of stroke in AF patients: refining the CHADS2 score, Int. J. Cardiol. 146 (2011) 131–133. C.C. Chang, C.C. Chiu, C.H. Chiang, C.C. Huang, W.L. Chan, P.H. Huang, Y.C. Chen, T.J. Chen, C.M. Chung, S.J. Lin, J.W. Chen, H.B. Leu, Obstructive sleep apnea and the risk of ischemic stroke in patients with atrial fibrillation, Int. J. Cardiol. 181C (2014) 144–146. F.M. Szymanski, A.E. Platek, G. Karpinski, E. Kozluk, B. Puchalski, K.J. Filipiak, Obstructive sleep apnoea in patients with atrial fibrillation: prevalence, determinants and clinical characteristics of patients in Polish population, Kardiol. Pol. 72 (2014) 716–724. F.M. Szymanski, K.J. Filipiak, A.E. Platek, A. Hrynkiewicz-Szymanska, G. Karpinski, G. Opolski, Assessment of CHADS2 and CHA2DS2-VASc scores in obstructive sleep apnea patients with atrial fibrillation, Sleep Breath. (2014) http://dx.doi.org/10. 1007/s11325-014-1042-5 (Ahead of print).
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Is obstructive sleep apnea associated with the risk of ischemic stroke in patients with atrial fibrillation? Filip M. Szymanski ⁎, Anna E. Platek, Krzysztof J. Filipiak 1st Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
a r t i c l e
i n f o
Article history: Received 13 January 2015 Accepted 24 February 2015 Available online 26 February 2015 Keywords: Atrial fibrillation Obstructive sleep apnea CHA2DS2-VASc CHADS2 Thromboembolic risk
Atrial fibrillation (AF) is one of the most important preventable causes of ischemic stroke. Current guidelines recommend assessing the thromboembolic risk by either CHADS2 or CHA2DS2-VASc scores [1]. Unfortunately, both scores base only on age and previously diagnosed comorbidities, and tend to omit many important aspects that strongly influence patients' risk and prognosis. Factors such as left atrial morphology and function or chronic kidney disease were previously shown to be associated with higher risk of stroke and influence the necessity of anticoagulation in atrial fibrillation patients [2,3]. Another factor which may bring additional value to the assessment of thromboembolic risk in AF patients is the presence of obstructive sleep apnea (OSA). OSA is one of the types of sleep disordered breathing most prevalent in the general population. In numerous, large, prospective studies OSA was shown to be associated with increased risk of stroke and death in the general population [4]. Thromboembolic risk associated with OSA is a cause of deep vein thrombosis, pulmonary embolism and in-stent thrombosis [5,6]. The concept of an increased thromboembolic risk associated with co-existence of OSA and AF, which exceeds the risk calculated by CHADS2 or CHA2DS2-VASc scores is not new. Yazdan-Ashoori and Baranchuk even proposed to include OSA in those schemes to increase their predictive value [7]. Nevertheless, there is still not enough data in the literature supporting this concept. Therefore, the more willingly the readers will probably welcome
⁎ Corresponding author at: 1st Department of Cardiology, Medical University of Warsaw, 1A Banacha Street, PL02-097 Warsaw, Poland. E-mail address: fi[email protected] (F.M. Szymanski).
http://dx.doi.org/10.1016/j.ijcard.2015.02.091 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
the work by Chang et al. published in the recent issue of the International Journal of Cardiology [8]. We would like to congratulate the authors of the study, which could provide interesting, new data on the topic. Unfortunately, there is a concern that some parts of the study methodology are not properly chosen, and therefore cause the main study finding to be to far gone. The main conclusion of the study is that adding OSA to CHA2DS2VASc does not improve its predictive value in AF patients. It was not properly proven. First of all the study did not include (all) OSA patients, but patients with “severe OSA requiring CPAP (continuous positive airway pressure) treatment” identified basing on a registry. It is a strictly specified subgroup. In order to receive CPAP treatment, OSA first needs to be properly diagnosed, which given the fact that the disease is largely underdiagnosed, will cause potential bias. Second of all, not every OSA patient requires CPAP treatment, and even those who do, do not always tolerate and adhere to the treatment. This is proven by the fact that only 0.8% of the AF patients enrolled into the study were considered as “having OSA”, which is even much less than in the general population. We have previously shown that in AF patients qualified for ablation (which account for a relatively young and healthy subgroup of AF population) the prevalence of all OSA is 45.49% [9]. Our study protocol required sleep-study screening in consecutive patients, regardless of their symptoms and therefore showed reliable data on the sleep disordered breathing prevalence. One would expect for the OSA prevalence in unselected AF patients to be at least as high or even higher. Moreover, few additional factors influence the findings. The major concern is that, the treatment with CPAP ameliorates all impact of OSA on stroke risk. It has been well documented that CPAP reverses hemodynamic, vascular, metabolic, and thrombotic changes caused by OSA. Data in this kind of study can be valid only if CPAP-naïve patients are considered. Also, a relatively small sample size (133 OSA patients) might be responsible for low statistical power. A small, but significant increase in some stroke risk factors in OSA patients was found; thus there is confounding for which the small sample size does not permit full adjustment. Also 1 point added a priori (without any statistical calculations) to the CHA2DS2-VASc score may be too much or too little. Maybe OSA would account to only 0.5 points, or contrary - event to 2 or 3 points, basing on the added risk? Thus, the improper selection of patients leads to the finding that OSA does not add to the predictive value of CHA2DS2-VASc cannot be predictive for the whole AF population, and in this context, their negative finding is less worthy.
482
F.M. Szymanski et al. / International Journal of Cardiology 184 (2015) 481–482
We still have to wait for a study, which would show if OSA is truly a factor that can add predictive value for the CHA2DS2-VASc or CHADS2 score. Nevertheless, there is already data that show that OSA patients have higher CHADS2 and CHA2DS2-VASc scores than patients without sleep disordered breathing. Also, mean CHADS2 and CHA2DS2-VASc scores rise with OSA severity and the differences in the stroke risk are significant even across different age strata, and the trend for point values in CHADS2 and CHA2DS2-VASc scores rises along with OSA severity according to the apnea–hypopnea index [10]. All these arguments show that AF patients with OSA do have higher thromboembolic risk, but whether it will add additional value to the stroke prediction models remains a field for further research. Conflict of interest
[3]
[4]
[5]
[6]
[7] [8]
The authors report no relationships that could be construed as a conflict of interest. References [1] A.J. Camm, G.Y. Lip, R. De Caterina, I. Savelieva, D. Atar, S.H. Hohnloser, G. Hindricks, P. Kirchhof, ESC Committee for Practice Guidelines (CPG), 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association, Eur. Heart J. 33 (2012) (2010) 2719–2747. [2] A. Hrynkiewicz-Szymanska, M. Dluzniewski, A.E. Platek, F.M. Szymanski, J. SyskaSuminska, A. Klos-Szadryn, M. Glinka, M. Strojek, A. Kuciej, M. Tomaszewska-
[9]
[10]
Kiecana, Association of the CHADS2 and CHA 2DS 2-VASc scores with left atrial enlargement: a prospective cohort study of unselected atrial fibrillation patients, J. Thromb. Thrombolysis (2014) http://dx.doi.org/10.1007/s11239-014-1154-6 (Ahead of print). A.N. Bonde, G.Y. Lip, A.L. Kamper, P.R. Hansen, M. Lamberts, K. Hommel, M.L. Hansen, G.H. Gislason, C. Torp-Pedersen, J.B. Olesen, Net clinical benefit of antithrombotic therapy in patients with atrial fibrillation and chronic kidney disease: a nationwide observational cohort study, J. Am. Coll. Cardiol. 64 (2014) 2471–2482. H.K. Yaggi, J. Concato, W.N. Kernan, J.H. Lichtman, L.M. Brass, V. Mohsenin, Obstructive sleep apnea as a risk factor for stroke and death, N. Engl. J. Med. 353 (2005) 2034–2041. Y.H. Peng, W.C. Liao, W.S. Chung, C.H. Muo, C.C. Chu, C.J. Liu, C.H. Kao, Association between obstructive sleep apnea and deep vein thrombosis/pulmonary embolism: a population-based retrospective cohort study, Thromb. Res. 134 (2014) 340–345. A. Hrynkiewicz-Szymanska, F.M. Szymanski, K.J. Filipiak, M. Grabowski, A. Dąbrowska-Kugacka, G. Karpinski, G. Opolski, Can obstructive sleep apnea be a cause of in-stent thrombosis? Sleep Breath. 15 (2011) 607–609. P. Yazdan-Ashoori, A. Baranchuk, Obstructive sleep apnea may increase the risk of stroke in AF patients: refining the CHADS2 score, Int. J. Cardiol. 146 (2011) 131–133. C.C. Chang, C.C. Chiu, C.H. Chiang, C.C. Huang, W.L. Chan, P.H. Huang, Y.C. Chen, T.J. Chen, C.M. Chung, S.J. Lin, J.W. Chen, H.B. Leu, Obstructive sleep apnea and the risk of ischemic stroke in patients with atrial fibrillation, Int. J. Cardiol. 181C (2014) 144–146. F.M. Szymanski, A.E. Platek, G. Karpinski, E. Kozluk, B. Puchalski, K.J. Filipiak, Obstructive sleep apnoea in patients with atrial fibrillation: prevalence, determinants and clinical characteristics of patients in Polish population, Kardiol. Pol. 72 (2014) 716–724. F.M. Szymanski, K.J. Filipiak, A.E. Platek, A. Hrynkiewicz-Szymanska, G. Karpinski, G. Opolski, Assessment of CHADS2 and CHA2DS2-VASc scores in obstructive sleep apnea patients with atrial fibrillation, Sleep Breath. (2014) http://dx.doi.org/10. 1007/s11325-014-1042-5 (Ahead of print).
