International Journal of Cardiology 181 (2015) 144–146
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Obstructive sleep apnea and the risk of ischemic stroke in patients with atrial fibrillation Chun-Chin Chang b,e, Chun-Chih Chiu b,e, Chia-Hung Chiang b,e, Chin-Chou Huang a,b,e, Wan-Leong Chan b,c, Po-Hsun Huang b,e,g, Yu-Chun Chen d,i, Tzeng-Ji Chen d,h, Chia-Min Chung j, Shing-Jong Lin a,b,e,g, Jaw-Wen Chen a,b,e,f, Hsin-Bang Leu b,c,e,g,⁎ a
Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan c Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan d Department of Family Medicine Taipei Veterans General Hospital, Taipei Veterans General Hospital, Taipei, Taiwan e Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan f Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan g Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan h Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan i Department of Medical Informatics, University of Heidelberg, Heidelberg, Germany j Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC b
a r t i c l e
i n f o
Article history: Received 26 November 2014 Accepted 1 December 2014 Available online 3 December 2014 Keywords: Atrial fibrillation Ischemic stroke
among AF patients and provide further predictive value in addition to CHA2DS2-VASc score. 1. Methods We used the National Health Insurance Research Database released by the Taiwan National Health Research Institutes. The National Health Insurance Research Database is a cohort dataset that contains all of the medical claims data for a random sampling of 1,000,000 beneficiaries from the 25.68 million enrollees in the National Health Insurance program. These random samples have been confirmed by the National Health Research Institutes to be representative of the Taiwanese population. 1.1. AF definition
Atrial fibrillation (AF) is associated with significant morbidity and mortality. Prevention of thromboembolism with oral anticoagulant agents is an important treatment for patients with AF. CHADS2 and CHA2DS2-VASc score has been widely used as the initial approach to assess future stroke risk among AF patients. Obstructive sleep apnea (OSA) is a common breathing disorder associated with substantial cardiovascular morbidity and mortality. It has been reported as an independent risk factor for ischemic stroke [1–4]. OSA may pose a threat to the cardiovascular system by several ways [1,5–7], such as chronic intermittent hypoxia, sympathetic hyperactivation, and systemic inflammation. Because of the close relationship between AF and OSA, it is interesting to know whether OSA could further provide greater predictive value of future adverse events for patients with AF. Therefore we conducted a study to investigate whether OSA is an independent predictor of ischemic stroke
⁎ Corresponding author at: Healthcare and Management Center, Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan. E-mail address: [email protected] (H.-B. Leu).
http://dx.doi.org/10.1016/j.ijcard.2014.12.019 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Patients with atrial fibrillation were enrolled according to criteria as followed: (1) age ≥18 years old, and (2) patients who were diagnosed per the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 427.31 during hospitalization or subsequent outpatient visits since January 1, 2000 to December 31, 2009. The age, sex, and comorbidities such as diabetes, hypertension, coronary artery disease, chronic renal disease, congestive heart failure, peripheral artery disease, chronic obstructive pulmonary disease, previous ischemic stroke and sleep apnea were identified. 1.2. OSA definition To avoid the interference from nonspecific symptoms of OSA, only these severe OSAs needing continuous positive airway pressure (CPAP) ventilator support were selected for analyses. Therefore, the severity of OSA in the study population belongs to OSA with higher disease severity and the association between future risks could be addressed. The identification of OSA by insurance claims data is valid and has been used in our previous work [8]. 1.3. Stroke event measurement The occurrence of ischemic stroke was identified by insurance claim. We only enrolled patients who had at least two administrative claims coded for ischemic stroke. Furthermore, the stroke event was identified according to any one of the following conditions: (1) hospitalization claims or (2) ≥3 consecutive outpatient visits to hospitals; followed either by claims for various neurological imaging technologies and long-term prescriptions used for ischemic stroke; or (3) by claims for rehabilitation and the long-term ischemic stroke prescriptions. Similar definition of stroke and more details have been described in our previous studies [9,10].
C.-C. Chang et al. / International Journal of Cardiology 181 (2015) 144–146
2. Results
Table 2 Comparison of AF patients with and without ischemic stroke.
A total of 17,375 patients with diagnosed AF were identified. Among these 17,375 subjects, a total of 133 patients with diagnosed OSA and needed CPAP treatment were identified. During the average follow-up period of 2.51 ± 2.60 years, 6938 AF patients experienced events of ischemic stroke. Subjects with concomitant AF and OSA had a higher percentage of hypertension, diabetes, chronic obstructive pulmonary disease, coronary artery disease, chronic kidney disease and peripheral arterial obstructive disease than those AF patients without OSA. Although OSA patients have a higher incidence of comorbidities, the baseline CHA2DS2-VASc score is also similar between both groups (Table 1). As shown in Table 2, patients with ischemic stroke were older, had more comorbidities and had higher CHA2DS2-VASc score than patients without event. However, there is no significant difference in OSA percentage between two groups. To further investigate the relationship between stroke incidences and the impact of adding OSA into well established CHA2DS2-VASc score, we compared stroke incidence according to whether OSA is added into CHA2DS2-VASc score. The Kaplan–Meier survival analysis showed the risk correlated with an increasing CHA2DS2-VASc score (p b 0.001) and adding OSA did not change the survival curve (Fig. 1), indicating that the trend of higher score correlated higher risk did not change even considering OSA. To further estimate the increased predictive value of adding OSA into CHA2DS2-VASc score, NRI and ROC curves were analyzed to evaluate the additional increased predictive value after considering OSA. The area under the ROC was almost the same (AUC = 0.66) and NRI was − 0.17% (p = 0.485), suggesting that adding OSA into original CHA2DS2-VASc score did not provide additional prediction benefit for risk stratification in patients with AF. Cox regression model was performed to investigate the independent risk factor in predicting
Table 1 Baseline characteristics of the study population. Total, n = 17,375
Age, years Male Hypertension Diabetes COPD Coronary artery disease Congestive heart failure Chronic renal disease Peripheral arterial obstructive disease History of Ischemic stroke Medication Antiplatelet drug Warfarin ACEI/ARB Statin CCB CHA2DS2-VASc score, mean Low risk (0 in men; 1 in woman) Score = 1 Score = 2 or more
145
Obstructive sleep apnea
Ischemic stroke
Age, years Male Hypertension Diabetes COPD Coronary artery disease Congestive heart failure Chronic renal disease Peripheral arterial obstructive disease History of Ischemic stroke Obstructive sleep apnea CHA2DS2-VASc score, mean Low risk (0 in men; 1 in woman) Score = 1 Score = 2 or more Medication Antiplatelet drug Warfarin ACEI/ARB Statin CCB
p value
No
Yes
(n = 10,437)
(n = 6938)
69.59 ± 13.98 5912 (56.6) 7675 (73.5) 3666 (35.1) 6140 (58.8) 6415 (61.4) 4547 (43.5) 2479 (23.7) 1530(14.6) 2857 (27.3) 88(0.8) 3.80 ± 2.15 848(8.1) 857(8.2) 8732(83.7)
73.83 ± 10.59 3816 (55.0) 5834 (84.0) 2738 (39.4) 4035 (58.1) 4622 (66.6) 3007 (43.3) 1671 (24.0) 1154(16.6) 4476 (64.5) 45(0.6) 4.97 ± 1.91 101(1.4) 199(2.9) 6638(95.7)
b0.001 0.034 b0.001 b0.001 0.387 b0.001 0.778 0.624 b0.001 b0.001 0.157 b0.001
4663 (44.6) 1282 (12.2) 4760(45.6) 1528 (14.6) 4902 (46.9)
5164 (74.4) 1489 (21.4) 3744 (53.9) 996 (14.3) 4252 (61.2)
b0.001 b0.001 b0.001 0.613 b0.001
Values are mean ± SD or n (%), ACEI: angiotensin-converting-enzyme inhibitor, ARB: angiotensin receptor blocker, COPD: chronic obstructive pulmonary disease, CCB: calcium channel blockers.
stroke among AF patients. After adjusting for the patients' age, gender, comorbidities and medications, only CHA2DS2-VASc score (HR = 1.78, 95% CI, 1.73–1.82; p b 0.001), especially the key factor of previous stroke history (HR = 4.11, 95% CI, 3.89–4.33; p b 0.001) is independently associated with increased risk of future ischemic stroke in patients with AF (Table 3). OSA did not provide similar predictive value as CHA2DS2-VASc score in predicting future ischemic event in patients with AF.
p value
n = 17,242
n = 133
No
Yes
71.28 ± 12.90 9728 (56) 13,509 (77.7) 6404 (36.9) 10,175(58.6) 11,037 (63.5)
71.30 ± 12.91 9646 (55.9) 13,389 (77.7) 6338 (36.8) 10,072(58.4) 10,938 (63.4)
69.62 ± 12.65 0.137 82 (61.7) 0.186 120 (90.2) 0.001 66 (49.6) 0.002 103(77.4) b0.001 99 (74.4) 0.009
7554 (43.5)
7494 (43.5)
60 (45.1)
0.702
4150 (23.9) 2684(15.4)
4107 (23.8) 2651(15.4)
43 (32.3) 33(24.8)
0.022 0.003
7333 (42.2)
7270 (42.2)
63 (47.4)
0.226
9827 (56.6) 2771 (15.9) 8504(48.9) 2524 (14.5) 9154 (52.7) 4.27 ± 2.13
9747 (56.5) 2751 (16.0) 8430(48.9) 2497 (14.5) 9074 (52.6) 4.27 ± 2.13
80 (60.2) 20 (15.0) 74 (55.6) 27 (20.3) 80 (60.2) 4.56 ± 2.13
0.401 0.773 0.121 0.058 0.083 0.121
1056 (6.0)
1048 (6.0)
8 (6.0)
949 (5.5) 15,370 (88.5)
948 (5.5) 15,246 (88.6)
1 (0.8) 124 (93.2)
3. Discussion
Values are mean ± SD or n (%), ACEI: angiotensin-converting-enzyme inhibitor, ARB: angiotensin receptor blocker, COPD: chronic obstructive pulmonary disease, CCB: calcium channel blockers.
Our pilot study demonstrated that OSA patients have more risk factors than patients without OSA. However, the future ischemic stroke risk for AF patients with OSA concomitantly is similar as AF patients without OSA. To our interest, despite the association between AF and OSA, our current study clearly demonstrated that the prognosis of AF was mainly determined by underling comorbidities and CHA2DS2-VASc score, not OSA. OSA did not increase the predictive value for risk stratification. We believed that it is reasonable because OSA and AF shared many risk factors. The risk factors underlying OSA seem to play a more important role. Although adding OSA to CHA2DS2-VASc score did not achieve statistical significance, OSA may affect through these risk factors of CHA2DS2-VASc score. The associations between AF and OSA still indicated that underlying comorbidities need to be controlled. OSA is often undiagnosed clinically. Apparently it warrants more aggressive treatment and surveillances when AF patients combined with OSA. In conclusion, adding OSA to CHA2DS2-VASc score could not improve its predictive valve in ischemic stroke in AF patients.
Conflict of interest The authors report no relationships that could be construed as a conflict of interest.
146
C.-C. Chang et al. / International Journal of Cardiology 181 (2015) 144–146
Fig. 1. Cumulative Hazard function curve of CHA2DS2-VASc score and new score (CHA2DS2-VASc + OSA).
Table 3 Results of multivariable Cox regression analysis. *Model 1
Obstructive sleep apnea Age, year, 1 s.d = 12.9 Sex (female) Hypertension Congestive heart failure Diabetes Previous Ischemic stroke Obstructive sleep apnea CHA2DS2-VASc score, 1 s.d = 2.137
*Model 2
Hazard ratio (95% CI)
p
Hazard ratio (95% CI)
p
0.803 (0.599-1.077) 1.233 (1.198–1.269) 1.066 (1.016–1.118) 1.214 (1.133–1.301) 1.083 (1.032–1.138) 1.033 (0.983–1.086) 4.243 (4.022–4.476) 0.821(0.613–1.101) 1.798 (1.755–1.843)
0.143 b0.001 0.009 b0.001 0.001 0.204 b0.001 0.188 b0.001
0.798 (0.588–1.058) 1.274 (1.235–1.313) 1.030 (0.981–1.080) 1.128 (1.051–1.211) 1.088 (1.036–1.143) 1.049 (0.998–1.103) 4.111 (3.897–4.337) 0.835 (0.623–1.120) 1.781 (1.737–1.826)
0.113 b0.001 0.234 0.001 0.001 0.061 b0.001 0.229 b0.001
*Model 1: adjusted with all comorbidities. *Model 2: adjusted with all comorbidities and medications including antiplatelet drug, anticoagulant, ACE inhibitor/ARB, statin, and calcium channel blockade.
References [1] J.M. Marin, S.J. Carrizo, E. Vicente, A.G. Agusti, Long-term cardiovascular outcomes in men with obstructive sleep apnoea–hypopnoea with or without treatment with continuous positive airway pressure: an observational study, Lancet 365 (9464) (2005) 1046–1053. [2] R. Munoz, J. Duran-Cantolla, E. Martinez-Vila, et al., Severe sleep apnea and risk of ischemic stroke in the elderly, Stroke 37 (9) (2006) 2317–2321. [3] 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 (19) (2005) 2034–2041. [4] F. Valham, T. Mooe, T. Rabben, H. Stenlund, U. Wiklund, K.A. Franklin, Increased risk of stroke in patients with coronary artery disease and sleep apnea: a 10-year followup, Circulation 118 (9) (2008) 955–960. [5] R. Kanagala, N.S. Murali, P.A. Friedman, et al., Obstructive sleep apnea and the recurrence of atrial fibrillation, Circulation 107 (20) (2003) 2589–2594.
[6] D.J. Gottlieb, G. Yenokyan, A.B. Newman, et al., Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure: the sleep heart health study, Circulation 122 (4) (2010) 352–360. [7] E.S. Arnardottir, M. Mackiewicz, T. Gislason, K.L. Teff, A.I. Pack, Molecular signatures of obstructive sleep apnea in adults: a review and perspective, Sleep 32 (4) (2009) 447–470. [8] K.T. Chou, C.C. Huang, Y.M. Chen, et al., Sleep apnea and risk of deep vein thrombosis: a non-randomized, pair-matched cohort study, Am. J. Med. 125 (4) (2012) 374–380. [9] C.H. Chiang, C.C. Huang, W.L. Chan, et al., Association between mycoplasma pneumonia and increased risk of ischemic stroke: a nationwide study, Stroke; a journal of cerebral circulation 42 (10) (2011) 2940–2943. [10] C.H. Chiang, C.J. Liu, C.C. Huang, et al., Systemic sclerosis and risk of ischaemic stroke: a nationwide cohort study, Rheumatology 52 (1) (2013) 161–165.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Obstructive sleep apnea and the risk of ischemic stroke in patients with atrial fibrillation Chun-Chin Chang b,e, Chun-Chih Chiu b,e, Chia-Hung Chiang b,e, Chin-Chou Huang a,b,e, Wan-Leong Chan b,c, Po-Hsun Huang b,e,g, Yu-Chun Chen d,i, Tzeng-Ji Chen d,h, Chia-Min Chung j, Shing-Jong Lin a,b,e,g, Jaw-Wen Chen a,b,e,f, Hsin-Bang Leu b,c,e,g,⁎ a
Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan c Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan d Department of Family Medicine Taipei Veterans General Hospital, Taipei Veterans General Hospital, Taipei, Taiwan e Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan f Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan g Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan h Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan i Department of Medical Informatics, University of Heidelberg, Heidelberg, Germany j Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC b
a r t i c l e
i n f o
Article history: Received 26 November 2014 Accepted 1 December 2014 Available online 3 December 2014 Keywords: Atrial fibrillation Ischemic stroke
among AF patients and provide further predictive value in addition to CHA2DS2-VASc score. 1. Methods We used the National Health Insurance Research Database released by the Taiwan National Health Research Institutes. The National Health Insurance Research Database is a cohort dataset that contains all of the medical claims data for a random sampling of 1,000,000 beneficiaries from the 25.68 million enrollees in the National Health Insurance program. These random samples have been confirmed by the National Health Research Institutes to be representative of the Taiwanese population. 1.1. AF definition
Atrial fibrillation (AF) is associated with significant morbidity and mortality. Prevention of thromboembolism with oral anticoagulant agents is an important treatment for patients with AF. CHADS2 and CHA2DS2-VASc score has been widely used as the initial approach to assess future stroke risk among AF patients. Obstructive sleep apnea (OSA) is a common breathing disorder associated with substantial cardiovascular morbidity and mortality. It has been reported as an independent risk factor for ischemic stroke [1–4]. OSA may pose a threat to the cardiovascular system by several ways [1,5–7], such as chronic intermittent hypoxia, sympathetic hyperactivation, and systemic inflammation. Because of the close relationship between AF and OSA, it is interesting to know whether OSA could further provide greater predictive value of future adverse events for patients with AF. Therefore we conducted a study to investigate whether OSA is an independent predictor of ischemic stroke
⁎ Corresponding author at: Healthcare and Management Center, Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan. E-mail address: [email protected] (H.-B. Leu).
http://dx.doi.org/10.1016/j.ijcard.2014.12.019 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Patients with atrial fibrillation were enrolled according to criteria as followed: (1) age ≥18 years old, and (2) patients who were diagnosed per the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 427.31 during hospitalization or subsequent outpatient visits since January 1, 2000 to December 31, 2009. The age, sex, and comorbidities such as diabetes, hypertension, coronary artery disease, chronic renal disease, congestive heart failure, peripheral artery disease, chronic obstructive pulmonary disease, previous ischemic stroke and sleep apnea were identified. 1.2. OSA definition To avoid the interference from nonspecific symptoms of OSA, only these severe OSAs needing continuous positive airway pressure (CPAP) ventilator support were selected for analyses. Therefore, the severity of OSA in the study population belongs to OSA with higher disease severity and the association between future risks could be addressed. The identification of OSA by insurance claims data is valid and has been used in our previous work [8]. 1.3. Stroke event measurement The occurrence of ischemic stroke was identified by insurance claim. We only enrolled patients who had at least two administrative claims coded for ischemic stroke. Furthermore, the stroke event was identified according to any one of the following conditions: (1) hospitalization claims or (2) ≥3 consecutive outpatient visits to hospitals; followed either by claims for various neurological imaging technologies and long-term prescriptions used for ischemic stroke; or (3) by claims for rehabilitation and the long-term ischemic stroke prescriptions. Similar definition of stroke and more details have been described in our previous studies [9,10].
C.-C. Chang et al. / International Journal of Cardiology 181 (2015) 144–146
2. Results
Table 2 Comparison of AF patients with and without ischemic stroke.
A total of 17,375 patients with diagnosed AF were identified. Among these 17,375 subjects, a total of 133 patients with diagnosed OSA and needed CPAP treatment were identified. During the average follow-up period of 2.51 ± 2.60 years, 6938 AF patients experienced events of ischemic stroke. Subjects with concomitant AF and OSA had a higher percentage of hypertension, diabetes, chronic obstructive pulmonary disease, coronary artery disease, chronic kidney disease and peripheral arterial obstructive disease than those AF patients without OSA. Although OSA patients have a higher incidence of comorbidities, the baseline CHA2DS2-VASc score is also similar between both groups (Table 1). As shown in Table 2, patients with ischemic stroke were older, had more comorbidities and had higher CHA2DS2-VASc score than patients without event. However, there is no significant difference in OSA percentage between two groups. To further investigate the relationship between stroke incidences and the impact of adding OSA into well established CHA2DS2-VASc score, we compared stroke incidence according to whether OSA is added into CHA2DS2-VASc score. The Kaplan–Meier survival analysis showed the risk correlated with an increasing CHA2DS2-VASc score (p b 0.001) and adding OSA did not change the survival curve (Fig. 1), indicating that the trend of higher score correlated higher risk did not change even considering OSA. To further estimate the increased predictive value of adding OSA into CHA2DS2-VASc score, NRI and ROC curves were analyzed to evaluate the additional increased predictive value after considering OSA. The area under the ROC was almost the same (AUC = 0.66) and NRI was − 0.17% (p = 0.485), suggesting that adding OSA into original CHA2DS2-VASc score did not provide additional prediction benefit for risk stratification in patients with AF. Cox regression model was performed to investigate the independent risk factor in predicting
Table 1 Baseline characteristics of the study population. Total, n = 17,375
Age, years Male Hypertension Diabetes COPD Coronary artery disease Congestive heart failure Chronic renal disease Peripheral arterial obstructive disease History of Ischemic stroke Medication Antiplatelet drug Warfarin ACEI/ARB Statin CCB CHA2DS2-VASc score, mean Low risk (0 in men; 1 in woman) Score = 1 Score = 2 or more
145
Obstructive sleep apnea
Ischemic stroke
Age, years Male Hypertension Diabetes COPD Coronary artery disease Congestive heart failure Chronic renal disease Peripheral arterial obstructive disease History of Ischemic stroke Obstructive sleep apnea CHA2DS2-VASc score, mean Low risk (0 in men; 1 in woman) Score = 1 Score = 2 or more Medication Antiplatelet drug Warfarin ACEI/ARB Statin CCB
p value
No
Yes
(n = 10,437)
(n = 6938)
69.59 ± 13.98 5912 (56.6) 7675 (73.5) 3666 (35.1) 6140 (58.8) 6415 (61.4) 4547 (43.5) 2479 (23.7) 1530(14.6) 2857 (27.3) 88(0.8) 3.80 ± 2.15 848(8.1) 857(8.2) 8732(83.7)
73.83 ± 10.59 3816 (55.0) 5834 (84.0) 2738 (39.4) 4035 (58.1) 4622 (66.6) 3007 (43.3) 1671 (24.0) 1154(16.6) 4476 (64.5) 45(0.6) 4.97 ± 1.91 101(1.4) 199(2.9) 6638(95.7)
b0.001 0.034 b0.001 b0.001 0.387 b0.001 0.778 0.624 b0.001 b0.001 0.157 b0.001
4663 (44.6) 1282 (12.2) 4760(45.6) 1528 (14.6) 4902 (46.9)
5164 (74.4) 1489 (21.4) 3744 (53.9) 996 (14.3) 4252 (61.2)
b0.001 b0.001 b0.001 0.613 b0.001
Values are mean ± SD or n (%), ACEI: angiotensin-converting-enzyme inhibitor, ARB: angiotensin receptor blocker, COPD: chronic obstructive pulmonary disease, CCB: calcium channel blockers.
stroke among AF patients. After adjusting for the patients' age, gender, comorbidities and medications, only CHA2DS2-VASc score (HR = 1.78, 95% CI, 1.73–1.82; p b 0.001), especially the key factor of previous stroke history (HR = 4.11, 95% CI, 3.89–4.33; p b 0.001) is independently associated with increased risk of future ischemic stroke in patients with AF (Table 3). OSA did not provide similar predictive value as CHA2DS2-VASc score in predicting future ischemic event in patients with AF.
p value
n = 17,242
n = 133
No
Yes
71.28 ± 12.90 9728 (56) 13,509 (77.7) 6404 (36.9) 10,175(58.6) 11,037 (63.5)
71.30 ± 12.91 9646 (55.9) 13,389 (77.7) 6338 (36.8) 10,072(58.4) 10,938 (63.4)
69.62 ± 12.65 0.137 82 (61.7) 0.186 120 (90.2) 0.001 66 (49.6) 0.002 103(77.4) b0.001 99 (74.4) 0.009
7554 (43.5)
7494 (43.5)
60 (45.1)
0.702
4150 (23.9) 2684(15.4)
4107 (23.8) 2651(15.4)
43 (32.3) 33(24.8)
0.022 0.003
7333 (42.2)
7270 (42.2)
63 (47.4)
0.226
9827 (56.6) 2771 (15.9) 8504(48.9) 2524 (14.5) 9154 (52.7) 4.27 ± 2.13
9747 (56.5) 2751 (16.0) 8430(48.9) 2497 (14.5) 9074 (52.6) 4.27 ± 2.13
80 (60.2) 20 (15.0) 74 (55.6) 27 (20.3) 80 (60.2) 4.56 ± 2.13
0.401 0.773 0.121 0.058 0.083 0.121
1056 (6.0)
1048 (6.0)
8 (6.0)
949 (5.5) 15,370 (88.5)
948 (5.5) 15,246 (88.6)
1 (0.8) 124 (93.2)
3. Discussion
Values are mean ± SD or n (%), ACEI: angiotensin-converting-enzyme inhibitor, ARB: angiotensin receptor blocker, COPD: chronic obstructive pulmonary disease, CCB: calcium channel blockers.
Our pilot study demonstrated that OSA patients have more risk factors than patients without OSA. However, the future ischemic stroke risk for AF patients with OSA concomitantly is similar as AF patients without OSA. To our interest, despite the association between AF and OSA, our current study clearly demonstrated that the prognosis of AF was mainly determined by underling comorbidities and CHA2DS2-VASc score, not OSA. OSA did not increase the predictive value for risk stratification. We believed that it is reasonable because OSA and AF shared many risk factors. The risk factors underlying OSA seem to play a more important role. Although adding OSA to CHA2DS2-VASc score did not achieve statistical significance, OSA may affect through these risk factors of CHA2DS2-VASc score. The associations between AF and OSA still indicated that underlying comorbidities need to be controlled. OSA is often undiagnosed clinically. Apparently it warrants more aggressive treatment and surveillances when AF patients combined with OSA. In conclusion, adding OSA to CHA2DS2-VASc score could not improve its predictive valve in ischemic stroke in AF patients.
Conflict of interest The authors report no relationships that could be construed as a conflict of interest.
146
C.-C. Chang et al. / International Journal of Cardiology 181 (2015) 144–146
Fig. 1. Cumulative Hazard function curve of CHA2DS2-VASc score and new score (CHA2DS2-VASc + OSA).
Table 3 Results of multivariable Cox regression analysis. *Model 1
Obstructive sleep apnea Age, year, 1 s.d = 12.9 Sex (female) Hypertension Congestive heart failure Diabetes Previous Ischemic stroke Obstructive sleep apnea CHA2DS2-VASc score, 1 s.d = 2.137
*Model 2
Hazard ratio (95% CI)
p
Hazard ratio (95% CI)
p
0.803 (0.599-1.077) 1.233 (1.198–1.269) 1.066 (1.016–1.118) 1.214 (1.133–1.301) 1.083 (1.032–1.138) 1.033 (0.983–1.086) 4.243 (4.022–4.476) 0.821(0.613–1.101) 1.798 (1.755–1.843)
0.143 b0.001 0.009 b0.001 0.001 0.204 b0.001 0.188 b0.001
0.798 (0.588–1.058) 1.274 (1.235–1.313) 1.030 (0.981–1.080) 1.128 (1.051–1.211) 1.088 (1.036–1.143) 1.049 (0.998–1.103) 4.111 (3.897–4.337) 0.835 (0.623–1.120) 1.781 (1.737–1.826)
0.113 b0.001 0.234 0.001 0.001 0.061 b0.001 0.229 b0.001
*Model 1: adjusted with all comorbidities. *Model 2: adjusted with all comorbidities and medications including antiplatelet drug, anticoagulant, ACE inhibitor/ARB, statin, and calcium channel blockade.
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