Editorial Comment Cardiology 2014;128:51–53 DOI: 10.1159/000357613
Received: November 26, 2013 Accepted: November 27, 2013 Published online: February 12, 2014
Hyperthyroid Atrial Fibrillation: Does It Matter for Stroke Risk? Marie-France Poulin a Rami Doukky a, b a
Division of Cardiology, Rush University Medical Center, and b Division of Adult Cardiology, John H. Stroger Jr. Hospital of Cook County, Chicago, Ill., USA
© 2014 S. Karger AG, Basel 0008–6312/14/1281–0051$39.50/0 E-Mail [email protected] www.karger.com/crd
patients found hyperthyroidism not to be independently predictive of stroke by multivariate analysis [13]. The prothrombotic state in hyperthyroidism has a biological basis. Many derangements in the coagulation system such as increased factors VIII and X activity, shorter activated partial thromboplastin time, higher fibrinogen levels and increased synthesis of acute phase reactants have been described [14]. Moreover, D-dimer level, a marker for fibrinolysis, has been found to be significantly higher in hyperthyroidism and to correlate with disease severity. D-dimer level was also identified as a predictor of thromboembolic events in AF [15]. In the present report, the authors studied 62 patients with hyperthyroid AF, comparing them to two control groups: non-thyroid AF (n = 107) and hyperthyroidism without AF (n = 100); all prospectively followed for a mean of 34 months. The authors found that the annual incidence of ischemic stroke was highest among hyperthyroid AF patients at 7.6% versus 3.6 and 0.7% in the non-thyroid AF and hyperthyroidism without AF groups, respectively [1]. Although the study groups were matched for stroke risk according to the CHA2DS2-VASc score, the Cox proportional hazards analysis indicated that hyperthyroid AF patients were at significantly higher stroke risk than non-thyroid AF patients with a hazard ratio of 3.2 (95% CI 1.01–5.59, p = 0.04), indicating that hyperthyroid AF is predictive of stroke risk above and beyond the CHA2DS2-VASc score. The study by Chen et al. [1] has many strengths, including consecutive patient selection and prospective followRami Doukky, MD Division of Cardiology, Rush University Medical Center 1653 West Congress Parkway Chicago, IL 60612 (USA) E-Mail rami_doukky @ rush.edu
Downloaded by: Lund University Libraries 130.235.66.10 - 8/25/2017 1:28:07 AM
In a recent issue of Cardiology, Chen et al. [1] reported on hypercoagulable state and stroke risk in hyperthyroid atrial fibrillation (AF). The existing evidence is not completely settled as to whether hyperthyroid AF is associated with a hypercoagulable state and constitutes an excess stroke risk, since the existing studies are small and observational in nature. This is reflected in discordant published guidelines [2, 3] and an inadequate adjudication of stroke risk in hyperthyroid AF as assessed by the CHADS2 and CHA2DS2-VASc scores [4, 5]. Thus, the present study is quite relevant as the authors prospectively compared stroke risk in a cohort of patients with hyperthyroid AF to two control groups: non-thyroid AF and hyperthyroid patients without AF. In this editorial comment, we examine the internal and external validity of this study and weigh-in on the controversy of stroke risk and recommendation for anticoagulation in hyperthyroid AF. It is well established that patients with hyperthyroidism are at significant risk for AF. However, stroke risk among hyperthyroid AF patients remains controversial. Many reports indicate that hyperthyroidism alone is associated with an increased stroke risk, with a reported incidence ranging from 2.4 to 26.7% [6–11]. Furthermore, strokes have even been observed with sinus rhythm and in young adults with hyperthyroidism and no other risk factors [6, 9, 12]. A study by Sheu et al. [12] suggested that thyrotoxic patients (without AF), as compared to euthyroid individuals, are at increased risk for ischemic stroke with a hazard ratio of 1.44. On the other hand, the Swedish Atrial Fibrillation cohort study of 182,678 AF
Table 1. Studies evaluating risk of stroke and systemic emboli in hyperthyroid AF Study
Design
Chen et al. [1]
prospective nested case control
Siu et al. [7]
prospective nested case control
Petersen and Hansen [6] Bar-Sela et al. [8]
HT + AF, n
Mean follow-up, months
Stroke, %
62
34
19.0
160
12
retrospective case control
91
retrospective case control
Staffurth et al. [9] retrospective case control
Systemic emboli, %
Annualized stroke, %
Stroke in controls, %
Annualized stroke in controls, %
–
7.6
8.4a 2.0b
3.6a 0.7b
9.4
–
9.4
3.1a 0.6b
3.1a 0.6b
39
13.2
–
4.1
2.9b
0.9b
30
NA
26.7
40.0
–
0b
0b
252
NA
2.4
4.4
–
0.8a 0.5b
–
Hurley et al. [10]
retrospective cross-sectional
68
NA
8.8
11.8
–
–
–
Yuen et al. [11]
case series
30
NA
NA
23.0
–
–
–
case series
42
NA
19.0
21.4
–
–
–
Davies et
al.c
HT = Hyperthyroidism; NA = not applicable or not available. Euthyroid AF. b HT without AF. c Unpubl. data; from Staffurth et al. [9].
a
52
Cardiology 2014;128:51–53 DOI: 10.1159/000357613
seems to be within the expected range, given the number of patients at risk and the low rate of anticoagulant use [5]. The study findings are in general agreement with the existing literature specifically addressing the risk of stroke associated with hyperthyroid AF, as summarized in table 1; all demonstrated relatively high rates of systemic emboli or stroke among patients with hyperthyroid AF [6–11] and some identified age as a predictor of stroke in these patients [6, 7, 10]. Only two previous studies included control groups; Siu et al. [7] demonstrated, in a fashion similar to this study, that hyperthyroid AF is associated with greater stroke risk than non-thyroid AF (p = 0.02) or hyperthyroidism without AF (p < 0.001), whereas Petersen and Hanson [6] compared hyperthyroid AF to hyperthyroidism without AF and demonstrated that hyperthyroid AF was not associated with increased stroke risk, after adjusting for the covariates age and gender (p = 0.17). However, the latter study did not include a non-thyroid AF control group. Therefore, no inference can be made from the Petersen and Hanson study [6] regarding the incremental risk posed by hyperthyroidism in AF patients. Clearly, the investigation by Chen et al. [1] is limited by the small sample size and number of events. The low rate of anticoagulation limits the applicability of the study findings in other practice settings. Although the present study demonstrated, by univariate analysis, that hyperthyroid Poulin /Doukky
Downloaded by: Lund University Libraries 130.235.66.10 - 8/25/2017 1:28:07 AM
up. Additionally, control groups were properly selected and matched to the hyperthyroid AF cohort on the basis of gender, age, hypertension and diabetes, in an apparent nested case-control design. Thus, the three study groups were well matched for stroke risk based on the CHA2DS2VASc score which allowed for better analysis of the incremental risk posed by hyperthyroid AF. Notably, only 6% and 5% of the hyperthyroid AF and non-thyroid AF patients, respectively, received oral anticoagulants. These are unusually low rates, given the proportion of patients at risk (CHA2DS2-VASc score ≥2). The low use of oral anticoagulants, however, allowed the investigators to study the ‘natural’ incidence of ischemic stroke in hyperthyroid AF, isolating the effect of hyperthyroidism. Furthermore, the low rate of anticoagulant use allowed for a relatively high stroke rate, providing the study adequate power despite the small sample size. As expected, among the few patients who were anticoagulated, warfarin was protective from stroke irrespective of the study group after adjusting for clinical covariates [OR = 0.45 (95% CI 0.07– 0.54), p = 0.01], suggesting that patients with hyperthyroid AF would benefit from full anticoagulation. Moreover, the stroke risk was increased in patients with a higher CHA2DS2-VASc score and in older individuals, which is consistent with the established literature. The reported 3.6% annual stroke rate in the non-thyroid AF group
AF patients have significantly higher mean D-dimer levels than both control groups, the authors could not demonstrate an association between D-dimer levels and stroke risk after adjusting for confounding covariates, such as study group, age and the CHA2DS2-VASc score, which is at odds with previous data. This could be attributed to collinearity between D-dimer levels and other confounding covariates, and it is possibly due to ‘over-fitting’ the Cox regression model, given the limited number of strokes observed. Furthermore, an interaction analysis between the study group and D-dimer level could have been helpful in understanding the interplay between hypercoagulability and hyperthyroid AF in determining stroke risk. The value of anticoagulation in preventing stroke in AF patients at risk is undisputed. It is common practice to assess a patient’s risk for stroke using the CHADS2 and CHA2DS2-VASc scores which were developed in a nonvalvular AF population at large [2, 3]. However, it is questionable whether these scoring systems adequately assess stroke risk in patients with hyperthyroid AF, as patients with this condition were too few to impact the findings of multivariate analysis in large nonvalvular AF cohorts used in the derivation of the aforementioned risk assessment schemes [4, 5]. Yet, the prevailing evidence from studies dedicated to hyperthyroid AF populations indicates that these patients are at increased risk of stroke as compared to non-thyroid AF. Therefore, it is plausible that hyperthyroid AF constitutes a unique entity in which
conventional risk assessment tools, such as the CHADS2 and CHA2DS2-VASc scores, are not applicable. Thus, the 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines give a class I recommendation (level of evidence C) for full anticoagulation of patients with thyrotoxicosis who develop AF, and once euthyroid state is restored, antithrombotic prophylaxis should be the same as for patients without hyperthyroidism [2]. On the other hand, the American College of Chest Physicians’ (ACCP) guidelines did not treat hyperthyroid AF as a distinct entity, recommending anticoagulation only on the basis of the CHADS2 score [3]. The present literature supports the ACCF/AHA guidelines on this issue and calls for updating the ACCP guidelines accordingly. A randomized clinical trial investigating the benefit of anticoagulation in hyperthyroid AF patients who are at otherwise low stroke risk is very much needed. In conclusion, awaiting more definitive evidence, patients with hyperthyroid AF should be considered at increased stroke risk and are likely to benefit from full anticoagulation until sinus rhythm and stable euthyroid state have been restored.
Conflict of Interest None.
References
Hyperthyroid AF: Does It Matter for Stroke Risk?
5 Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ: Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factorbased approach: the Euro Heart Survey on atrial fibrillation. Chest 2010;137:263–272. 6 Petersen P, Hansen JM: Stroke in thyrotoxicosis with atrial fibrillation. Stroke 1988; 19: 15–18. 7 Siu CW, Pong V, Zhang XH, Chan YH, Jim MH, Liu SS, Yiu KH, Kung AWC, Lau CP, Tse HF: Risk of ischemic stroke after new-onset atrial fibrillation in patients with hyperthyroidism. Heart Rhythm 2009;6:169–173. 8 Bar-Sela S, Ehrenfeld M, Eliakim M: Arterial embolism in thyrotoxicosis with atrial fibrillation. Arch Intern Med 1981;141:1191–1192. 9 Staffurth JS, Gibberd MC, Fui SN: Arterial embolism in thyrotoxicosis with atrial fibrillation. Br Med J 1977;2:688–690. 10 Hurley DM, Hunter AN, Hewett MJ, Stockigt JR: Atrial fibrillation and arterial embolism in hyperthyroidism. Aust NZ J Med 1981; 11: 391–393.
11 Yuen RW, Gutteridge DH, Thompson PL, Robinson JS: Embolism in thyrotoxic atrial fibrillation. Med J Aust 1979;1:630–631. 12 Sheu JJ, Kang JH, Lin HC: Hyperthyroidism and risk of ischemic stroke in young adults: a 5-year follow-up study. Stroke 2010; 41: 961– 966. 13 Friberg L, Rosenqvist M, Lip GY: Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182,678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J 2012;33:1500– 1510. 14 Franchini M, Montagnana M, Manzato F, Vescovi PP: Thyroid dysfunction and hemostasis: an issue still unresolved. Semin Thromb Hemost 2009;35:288–294. 15 Nozawa T, Inoue H, Hirai T, Iwasa A, Okumura K, Lee JD, Shimizu A, Hayano M, Yano K: D-dimer level influences thromboembolic events in patients with atrial fibrillation. Int J Cardiol 2006;109:59–65.
Cardiology 2014;128:51–53 DOI: 10.1159/000357613
53
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1 Chen Q, Yan Y, Zhang L, Cheng K, Liu Y, Zhu W: Effect of hyperthyroidism on the hypercoagulable state and thromboembolic events in patients with atrial fibrillation. Cardiology 2014;127:176–182. 2 Wann LS, Curtis AB, January CT, et al: 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2011;57:223–242. 3 Singer DE, Albers GW, Dalen JE, Fang MC, Go AS, Halperin JL, Lip GY, Manning WJ: Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 2008; 133: 546S–592S. 4 Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ: Validation of clinical classification schemes for predicting stroke: results from the national registry of atrial fibrillation. JAMA 2001;285:2864–2870.
Received: November 26, 2013 Accepted: November 27, 2013 Published online: February 12, 2014
Hyperthyroid Atrial Fibrillation: Does It Matter for Stroke Risk? Marie-France Poulin a Rami Doukky a, b a
Division of Cardiology, Rush University Medical Center, and b Division of Adult Cardiology, John H. Stroger Jr. Hospital of Cook County, Chicago, Ill., USA
© 2014 S. Karger AG, Basel 0008–6312/14/1281–0051$39.50/0 E-Mail [email protected] www.karger.com/crd
patients found hyperthyroidism not to be independently predictive of stroke by multivariate analysis [13]. The prothrombotic state in hyperthyroidism has a biological basis. Many derangements in the coagulation system such as increased factors VIII and X activity, shorter activated partial thromboplastin time, higher fibrinogen levels and increased synthesis of acute phase reactants have been described [14]. Moreover, D-dimer level, a marker for fibrinolysis, has been found to be significantly higher in hyperthyroidism and to correlate with disease severity. D-dimer level was also identified as a predictor of thromboembolic events in AF [15]. In the present report, the authors studied 62 patients with hyperthyroid AF, comparing them to two control groups: non-thyroid AF (n = 107) and hyperthyroidism without AF (n = 100); all prospectively followed for a mean of 34 months. The authors found that the annual incidence of ischemic stroke was highest among hyperthyroid AF patients at 7.6% versus 3.6 and 0.7% in the non-thyroid AF and hyperthyroidism without AF groups, respectively [1]. Although the study groups were matched for stroke risk according to the CHA2DS2-VASc score, the Cox proportional hazards analysis indicated that hyperthyroid AF patients were at significantly higher stroke risk than non-thyroid AF patients with a hazard ratio of 3.2 (95% CI 1.01–5.59, p = 0.04), indicating that hyperthyroid AF is predictive of stroke risk above and beyond the CHA2DS2-VASc score. The study by Chen et al. [1] has many strengths, including consecutive patient selection and prospective followRami Doukky, MD Division of Cardiology, Rush University Medical Center 1653 West Congress Parkway Chicago, IL 60612 (USA) E-Mail rami_doukky @ rush.edu
Downloaded by: Lund University Libraries 130.235.66.10 - 8/25/2017 1:28:07 AM
In a recent issue of Cardiology, Chen et al. [1] reported on hypercoagulable state and stroke risk in hyperthyroid atrial fibrillation (AF). The existing evidence is not completely settled as to whether hyperthyroid AF is associated with a hypercoagulable state and constitutes an excess stroke risk, since the existing studies are small and observational in nature. This is reflected in discordant published guidelines [2, 3] and an inadequate adjudication of stroke risk in hyperthyroid AF as assessed by the CHADS2 and CHA2DS2-VASc scores [4, 5]. Thus, the present study is quite relevant as the authors prospectively compared stroke risk in a cohort of patients with hyperthyroid AF to two control groups: non-thyroid AF and hyperthyroid patients without AF. In this editorial comment, we examine the internal and external validity of this study and weigh-in on the controversy of stroke risk and recommendation for anticoagulation in hyperthyroid AF. It is well established that patients with hyperthyroidism are at significant risk for AF. However, stroke risk among hyperthyroid AF patients remains controversial. Many reports indicate that hyperthyroidism alone is associated with an increased stroke risk, with a reported incidence ranging from 2.4 to 26.7% [6–11]. Furthermore, strokes have even been observed with sinus rhythm and in young adults with hyperthyroidism and no other risk factors [6, 9, 12]. A study by Sheu et al. [12] suggested that thyrotoxic patients (without AF), as compared to euthyroid individuals, are at increased risk for ischemic stroke with a hazard ratio of 1.44. On the other hand, the Swedish Atrial Fibrillation cohort study of 182,678 AF
Table 1. Studies evaluating risk of stroke and systemic emboli in hyperthyroid AF Study
Design
Chen et al. [1]
prospective nested case control
Siu et al. [7]
prospective nested case control
Petersen and Hansen [6] Bar-Sela et al. [8]
HT + AF, n
Mean follow-up, months
Stroke, %
62
34
19.0
160
12
retrospective case control
91
retrospective case control
Staffurth et al. [9] retrospective case control
Systemic emboli, %
Annualized stroke, %
Stroke in controls, %
Annualized stroke in controls, %
–
7.6
8.4a 2.0b
3.6a 0.7b
9.4
–
9.4
3.1a 0.6b
3.1a 0.6b
39
13.2
–
4.1
2.9b
0.9b
30
NA
26.7
40.0
–
0b
0b
252
NA
2.4
4.4
–
0.8a 0.5b
–
Hurley et al. [10]
retrospective cross-sectional
68
NA
8.8
11.8
–
–
–
Yuen et al. [11]
case series
30
NA
NA
23.0
–
–
–
case series
42
NA
19.0
21.4
–
–
–
Davies et
al.c
HT = Hyperthyroidism; NA = not applicable or not available. Euthyroid AF. b HT without AF. c Unpubl. data; from Staffurth et al. [9].
a
52
Cardiology 2014;128:51–53 DOI: 10.1159/000357613
seems to be within the expected range, given the number of patients at risk and the low rate of anticoagulant use [5]. The study findings are in general agreement with the existing literature specifically addressing the risk of stroke associated with hyperthyroid AF, as summarized in table 1; all demonstrated relatively high rates of systemic emboli or stroke among patients with hyperthyroid AF [6–11] and some identified age as a predictor of stroke in these patients [6, 7, 10]. Only two previous studies included control groups; Siu et al. [7] demonstrated, in a fashion similar to this study, that hyperthyroid AF is associated with greater stroke risk than non-thyroid AF (p = 0.02) or hyperthyroidism without AF (p < 0.001), whereas Petersen and Hanson [6] compared hyperthyroid AF to hyperthyroidism without AF and demonstrated that hyperthyroid AF was not associated with increased stroke risk, after adjusting for the covariates age and gender (p = 0.17). However, the latter study did not include a non-thyroid AF control group. Therefore, no inference can be made from the Petersen and Hanson study [6] regarding the incremental risk posed by hyperthyroidism in AF patients. Clearly, the investigation by Chen et al. [1] is limited by the small sample size and number of events. The low rate of anticoagulation limits the applicability of the study findings in other practice settings. Although the present study demonstrated, by univariate analysis, that hyperthyroid Poulin /Doukky
Downloaded by: Lund University Libraries 130.235.66.10 - 8/25/2017 1:28:07 AM
up. Additionally, control groups were properly selected and matched to the hyperthyroid AF cohort on the basis of gender, age, hypertension and diabetes, in an apparent nested case-control design. Thus, the three study groups were well matched for stroke risk based on the CHA2DS2VASc score which allowed for better analysis of the incremental risk posed by hyperthyroid AF. Notably, only 6% and 5% of the hyperthyroid AF and non-thyroid AF patients, respectively, received oral anticoagulants. These are unusually low rates, given the proportion of patients at risk (CHA2DS2-VASc score ≥2). The low use of oral anticoagulants, however, allowed the investigators to study the ‘natural’ incidence of ischemic stroke in hyperthyroid AF, isolating the effect of hyperthyroidism. Furthermore, the low rate of anticoagulant use allowed for a relatively high stroke rate, providing the study adequate power despite the small sample size. As expected, among the few patients who were anticoagulated, warfarin was protective from stroke irrespective of the study group after adjusting for clinical covariates [OR = 0.45 (95% CI 0.07– 0.54), p = 0.01], suggesting that patients with hyperthyroid AF would benefit from full anticoagulation. Moreover, the stroke risk was increased in patients with a higher CHA2DS2-VASc score and in older individuals, which is consistent with the established literature. The reported 3.6% annual stroke rate in the non-thyroid AF group
AF patients have significantly higher mean D-dimer levels than both control groups, the authors could not demonstrate an association between D-dimer levels and stroke risk after adjusting for confounding covariates, such as study group, age and the CHA2DS2-VASc score, which is at odds with previous data. This could be attributed to collinearity between D-dimer levels and other confounding covariates, and it is possibly due to ‘over-fitting’ the Cox regression model, given the limited number of strokes observed. Furthermore, an interaction analysis between the study group and D-dimer level could have been helpful in understanding the interplay between hypercoagulability and hyperthyroid AF in determining stroke risk. The value of anticoagulation in preventing stroke in AF patients at risk is undisputed. It is common practice to assess a patient’s risk for stroke using the CHADS2 and CHA2DS2-VASc scores which were developed in a nonvalvular AF population at large [2, 3]. However, it is questionable whether these scoring systems adequately assess stroke risk in patients with hyperthyroid AF, as patients with this condition were too few to impact the findings of multivariate analysis in large nonvalvular AF cohorts used in the derivation of the aforementioned risk assessment schemes [4, 5]. Yet, the prevailing evidence from studies dedicated to hyperthyroid AF populations indicates that these patients are at increased risk of stroke as compared to non-thyroid AF. Therefore, it is plausible that hyperthyroid AF constitutes a unique entity in which
conventional risk assessment tools, such as the CHADS2 and CHA2DS2-VASc scores, are not applicable. Thus, the 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines give a class I recommendation (level of evidence C) for full anticoagulation of patients with thyrotoxicosis who develop AF, and once euthyroid state is restored, antithrombotic prophylaxis should be the same as for patients without hyperthyroidism [2]. On the other hand, the American College of Chest Physicians’ (ACCP) guidelines did not treat hyperthyroid AF as a distinct entity, recommending anticoagulation only on the basis of the CHADS2 score [3]. The present literature supports the ACCF/AHA guidelines on this issue and calls for updating the ACCP guidelines accordingly. A randomized clinical trial investigating the benefit of anticoagulation in hyperthyroid AF patients who are at otherwise low stroke risk is very much needed. In conclusion, awaiting more definitive evidence, patients with hyperthyroid AF should be considered at increased stroke risk and are likely to benefit from full anticoagulation until sinus rhythm and stable euthyroid state have been restored.
Conflict of Interest None.
References
Hyperthyroid AF: Does It Matter for Stroke Risk?
5 Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ: Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factorbased approach: the Euro Heart Survey on atrial fibrillation. Chest 2010;137:263–272. 6 Petersen P, Hansen JM: Stroke in thyrotoxicosis with atrial fibrillation. Stroke 1988; 19: 15–18. 7 Siu CW, Pong V, Zhang XH, Chan YH, Jim MH, Liu SS, Yiu KH, Kung AWC, Lau CP, Tse HF: Risk of ischemic stroke after new-onset atrial fibrillation in patients with hyperthyroidism. Heart Rhythm 2009;6:169–173. 8 Bar-Sela S, Ehrenfeld M, Eliakim M: Arterial embolism in thyrotoxicosis with atrial fibrillation. Arch Intern Med 1981;141:1191–1192. 9 Staffurth JS, Gibberd MC, Fui SN: Arterial embolism in thyrotoxicosis with atrial fibrillation. Br Med J 1977;2:688–690. 10 Hurley DM, Hunter AN, Hewett MJ, Stockigt JR: Atrial fibrillation and arterial embolism in hyperthyroidism. Aust NZ J Med 1981; 11: 391–393.
11 Yuen RW, Gutteridge DH, Thompson PL, Robinson JS: Embolism in thyrotoxic atrial fibrillation. Med J Aust 1979;1:630–631. 12 Sheu JJ, Kang JH, Lin HC: Hyperthyroidism and risk of ischemic stroke in young adults: a 5-year follow-up study. Stroke 2010; 41: 961– 966. 13 Friberg L, Rosenqvist M, Lip GY: Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182,678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J 2012;33:1500– 1510. 14 Franchini M, Montagnana M, Manzato F, Vescovi PP: Thyroid dysfunction and hemostasis: an issue still unresolved. Semin Thromb Hemost 2009;35:288–294. 15 Nozawa T, Inoue H, Hirai T, Iwasa A, Okumura K, Lee JD, Shimizu A, Hayano M, Yano K: D-dimer level influences thromboembolic events in patients with atrial fibrillation. Int J Cardiol 2006;109:59–65.
Cardiology 2014;128:51–53 DOI: 10.1159/000357613
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1 Chen Q, Yan Y, Zhang L, Cheng K, Liu Y, Zhu W: Effect of hyperthyroidism on the hypercoagulable state and thromboembolic events in patients with atrial fibrillation. Cardiology 2014;127:176–182. 2 Wann LS, Curtis AB, January CT, et al: 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2011;57:223–242. 3 Singer DE, Albers GW, Dalen JE, Fang MC, Go AS, Halperin JL, Lip GY, Manning WJ: Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 2008; 133: 546S–592S. 4 Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ: Validation of clinical classification schemes for predicting stroke: results from the national registry of atrial fibrillation. JAMA 2001;285:2864–2870.
