International Journal of Cardiology 185 (2015) 301–303
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Psoriasis and risk of atrial fibrillation Zhiwei Zhang, Guangping Li, Tong Liu ⁎ Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China
a r t i c l e
i n f o
Article history: Received 12 March 2015 Accepted 15 March 2015 Available online 17 March 2015 Keyword: Psoriasis Atrial fibrillation Risk
Psoriasis is one of the most prevalent T-cell-mediated chronic inflammatory disorders affecting the skin, scalp, nails, and occasionally, joints. The prevalence of psoriasis in the general population ranged from 1% to 4% in population-based studies [1–3]. In recent years, several studies demonstrated that psoriasis is associated with an increased risk of cardiovascular (CV) diseases such as stroke, myocardial infarction (MI), peripheral vascular disease and CV death [4–11]. In a recently published review in the International Journal of Cardiology, Mosca et al. assessed the potential correlation between psoriasis and cardiovascular events including cerebrovascular accident, MI, thrombophlebitis, pulmonary embolism and CV mortality [12]. However, the authors did not mention the potential association between psoriasis and atrial fibrillation (AF) which is the most common sustained cardiac arrhythmia encountered in clinical practice and is associated with increased risk of morbidity and mortality [13]. We previously proposed a hypothesis on the possible relation among psoriasis, inflammation and AF [14]. In the past few years, there is increased evidence (Table 1) regarding the potential association between psoriasis and AF, and we intend to summarize the recent evidence on this issue. A Danish nationwide cohort study was first to analyze the risk of AF in the patients with psoriasis. Altogether, 36,765 patients with mild and 2793 patients with severe psoriasis were enrolled to compare with 4,478,926 subjects without psoriasis. The authors showed that in the patients with mild psoriasis, the adjusted risk ratios (RRs) for AF were 1.50 (95% CI: 1.21–1.86) in those under 50 and 1.16 (1.08–1.24) in the patients over 50 years, respectively. And in the patients with severe ⁎ Corresponding author at: Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China. E-mail address: [email protected] (T. Liu).
http://dx.doi.org/10.1016/j.ijcard.2015.03.149 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
psoriasis, a higher risk of AF was observed with RR = 2.98 (95% CI: 1.80–4.92) in those under 50 and 1.29 (95% CI: 1.01–1.65) in the patients over 50 years, suggesting that psoriasis was associated with an increased risk of AF independent of age, gender, co-morbidity, concomitant medication, and socioeconomic status. Furthermore, these also demonstrated that earlier onset psoriasis is more strongly associated with AF and the association has shown a consistent dose– response relationship between psoriasis severity and risk of AF [15]. More recently, Bang et al. [16] performed a propensity-matched analysis on 7099 hypertensive patients (154 with psoriasis) enrolled in LIFE study; they also demonstrated that psoriasis was independently associated with increased risk of new-onset AF. However, another epidemiologic study [17] reported the conflicting results from previous findings. Armstrong et al. assessed two cohorts including one cohort enrolled the patients with established cardiovascular disease (mean age N 60) and another larger cohort of out-patient psoriasis patients (mean age N 50). They suggested that there was no association between psoriasis and development of AF. In addition, they also suggested that there was no significantly increased incidence of AF for moderate-to-severe psoriasis patients as compared to the patients with mild psoriasis or the control subjects. Several pathophysiological mechanisms have been proposed as being responsible for the association linking psoriasis with AF. There is an increased interest in evaluating P-wave dispersion (PWD), which is an electrocardiographic marker related to inhomogeneous and discontinuous distribution of sinus impulse [18,19]. Besides, PWD is regarded as a marker of prolongation of intra-atrial and inter-atrial conduction time [20]. Prolonged PWD has been demonstrated to carry an increased risk for the development of AF [19,21]. Also, atrial electromechanical delay (AEMD), which shows the intra-atrial and inter-atrial conduction properties, has been associated with increased risk of AF occurrence [22, 23]. Prolongation of the duration of atrial PWD [24–27] and AEMD [24, 25] in the psoriasis patients compared with healthy controls was reported in several recently published studies. Additionally, PWD [24,27] and AEMD [25] were correlated with psoriasis area and severity index (PASI), which was used to determine the severity of psoriasis. All of these showed that atrial conduction function which may lead to AF was impaired in patients with psoriasis, and the damage was associated with the severity of psoriasis. Prolonged PWD and AEMD may due to electrophysiological and structural changes of the atrium that caused by the inflammation for the higher neutrophil to lymphocyte ratio (NLR) [24] and C-reactive protein (CRP) [25,27] levels in psoriasis patients compared with healthy controls. In addition, our previous studies have demonstrated that
302
Z. Zhang et al. / International Journal of Cardiology 185 (2015) 301–303
Table 1 Summary of the three epidemiologic studies regarding AF risk in patients with psoriasis. First author (year) [ref]
Patients (n)
Study design
Endpoints
Mean or median follow-up (years)
Risk of AF
Ahlehoff et al. (2012) [15]
4,518,484 (36,765 patients with mild psoriasis; 2793 patients with severe psoriasis)
Prospective
AF; ischemic stroke
Reference population: 9.2 (mean); mild psoriasis: 5.0 (mean); severe psoriasis: 4.7 (mean)
Bang et al. (2014) [16]
7099 (154 patients with psoriasis) Prospective; randomized; double-blind
AF; HF (secondary endpoint)
4.7 ± 1.1 (mean)
Armstrong et al. (2013) [17]
507 (169 patients with psoriasis)
AF
NA
Mild Patients aged b 50 years: Adjusted psoriasis RR 1.50 (95% CI, 1.21–1.86) Patients aged ≥50 years: Adjusted RR 1.16 (95% CI, 1.08–1.24) Severe Patients aged b 50 years: Adjusted psoriasis RR 2.98 (95% CI, 1.80–4.92) Patients aged ≥ 50 years: Adjusted RR 1.29 (95% CI, 1.01–1.65) Multivariable Cox analysis: HR 1.97 (95% CI, 1.18–3.30; P = 0.010); propensity-matched analysis: OR 3.49 (95% CI, 1.24–9.81, P = 0.018) All psoriasis: 12.8 vs. 14.6% over a 10-year period, P = 0.06 Moderate-to-severe psoriasis: 11.5 vs. 12.7% over a 10-year period, P = 0.6 All psoriasis: HR 0.9 (95% CI 0.5–1.8, P = 0.8) Moderate-to-severe psoriasis: HR 2.0 (95% CI, 0.5–7.8, P = 0.3) Patients aged b 50 years: HR 0.59 (95% CI, 0.17–2.0) Patients aged ≥ 50 years: HR 1.2 (95% CI, 0.85–1.7) Mild psoriasis: adjusted HR 1.32 (95% CI, 0.91–1.89) Moderate to severe psoriasis: adjusted HR 1.27 (95% CI, 0.54–3.03)
Framingham risk score for AF
Prospective
8312 (1773 patients with mild psoriasis; 305 patients with moderate to severe psoriasis)
Prospective
2.5 (median)
AF
4.3 (mean)
AF = atrial fibrillation; HF = heart failure; RR = rate ratios; HR = hazard ratio; OR = odds ratio; CI = confidence interval; NA = not applicable.
inflammation state manifested by elevated CRP levels, was associated with a greater risk of AF [28,29]. As well as systemic inflammatory response, oxidative stress was also suggested to be one of the most important mechanisms in the development of psoriasis [30,31], and former studies have also demonstrated the possible implication of oxidative stress in increasing the AF development risk by facilitating atrial electrophysiological and structural remodeling [32,33]. Thus, inflammatory process and oxidative stress seemed to be the lines that linked psoriasis and AF. In conclusion, although the exact etiology of increased risk of AF in psoriasis patients is still not fully understood, accumulating evidence suggests that systemic inflammatory response and oxidative stress may be responsible for the increased prevalence of AF in patients with psoriasis. Whether anti-inflammatory and anti-oxidative agents have beneficial effects on the prevention of AF in the patients with psoriasis remains to be determined. Recent data have demonstrated that statins, with anti-inflammatory and anti-oxidative effects, reduce the incidence of both AF and psoriasis [34–36] which may serve as promising therapies for the prevention of AF in the patients with psoriasis.
Conflict of interest None.
Financial disclosures None.
Acknowledgments This study was partly supported by grants (30900618, 81270245 to T.L.) from the National Natural Science Foundation of China.
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Z. Zhang et al. / International Journal of Cardiology 185 (2015) 301–303 [16] C.N. Bang, P.M. Okin, L. Kober, K. Wachtell, A.B. Gottlieb, R.B. Devereux, Psoriasis is associated with subsequent atrial fibrillation in hypertensive patients with left ventricular hypertrophy: the Losartan Intervention For Endpoint study, J. Hypertens. 32 (2014) 667–672. [17] A.W. Armstrong, S. Azizi, J. Wu, C.T. Harskamp, J. Farrow, M.A. Johnson, K. Klem, D. Anderson, E.J. Armstrong, Psoriasis, electrocardiographic characteristics, and incidence of atrial fibrillation, Arch. Dermatol. Res. 305 (2013) 891–897. [18] P.E. Dilaveris, E.J. Gialafos, G.K. Andrikopoulos, D.J. Richter, V. Papanikolaou, K. Poralis, J.E. Gialafos, Clinical and electrocardiographic predictors of recurrent atrial fibrillation, Pacing Clin. Electrophysiol. 23 (2000) 352–358. [19] P.E. Dilaveris, E.J. Gialafos, S.K. Sideris, A.M. Theopistou, G.K. Andrikopoulos, M. Kyriakidis, J.E. Gialafos, P.K. Toutouzas, Simple electrocardiographic markers for the prediction of paroxysmal idiopathic atrial fibrillation, Am. Heart J. 135 (1998) 733–738. [20] O.A. Centurion, Clinical implications of the P wave duration and dispersion: relationship between atrial conduction defects and abnormally prolonged and fractionated atrial endocardial electrograms, Int. J. Cardiol. 134 (2009) 6–8. [21] N. Ozer, K. Aytemir, E. Atalar, E. Sade, S. Aksoyek, K. Ovunc, T. Acyl, N. Nazly, F. Ozmen, A. Oto, S. Kes, P wave dispersion in hypertensive patients with paroxysmal atrial fibrillation, Pacing Clin. Electrophysiol. 23 (2000) 1859–1862. [22] Q.Q. Cui, W. Zhang, H. Wang, X. Sun, R. Wang, H.Y. Yang, X.Q. Meng, Y. Zhang, H. Wang, Assessment of atrial electromechanical coupling and influential factors in nonrheumatic paroxysmal atrial fibrillation, Clin. Cardiol. 31 (2008) 74–78. [23] W. Omi, H. Nagai, M. Takamura, S. Okura, M. Okajima, H. Furusho, M. Maruyama, S. Sakagami, S. Takata, S. Kaneko, Doppler tissue analysis of atrial electromechanical coupling in paroxysmal atrial fibrillation, J. Am. Soc. Echocardiogr. 18 (2005) 39–44. [24] A. Yildiz, D. Ucmak, M. Oylumlu, M.Z. Akkurt, M. Yuksel, M.A. Akil, H. Acet, N. Polat, M. Aydin, M.Z. Bilik, Assessment of atrial electromechanical delay and P-wave dispersion in patients with psoriasis, Echocardiography 31 (2014) 1071–1076. [25] G. Aksan, G. Nar, K. Soylu, S. Inci, S. Yuksel, H.S. Ocal, E.P. Yuksel, O. Gulel, Assessment of atrial electromechanical delay and left atrial mechanical functions in patients with psoriasis vulgaris, Echocardiography (2014, Aug 13)http://dx.doi. org/10.1111/echo.12706.
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[26] H. Simsek, M. Sahin, A. Akyol, S. Akdag, H.U. Ozkol, H.A. Gumrukcuoglu, Y. Gunes, Increased risk of atrial and ventricular arrhythmia in long-lasting psoriasis patients, Scientific World Journal 2013 (2013) 901215. [27] A. Bacaksiz, E. Erdogan, A. Tasal, M.A. Vatankulu, S. Kul, E. Sevgili, G. Ertas, D. Dizman, N. Onsun, O. Uysal, Electrocardiographic P-wave characteristics in patients with psoriasis vulgaris, Ups. J. Med. Sci. 118 (2013) 35–41. [28] T. Liu, L. Li, P. Korantzopoulos, J.A. Goudevenos, G. Li, Meta-analysis of association between C-reactive protein and immediate success of electrical cardioversion in persistent atrial fibrillation, Am. J. Cardiol. 101 (2008) 1749–1752. [29] T. Liu, G. Li, L. Li, P. Korantzopoulos, Association between C-reactive protein and recurrence of atrial fibrillation after successful electrical cardioversion: a metaanalysis, J. Am. Coll. Cardiol. 49 (2007) 1642–1648. [30] V.J. Friedewald, J.C. Cather, K.B. Gordon, A. Kavanaugh, P.M. Ridker, W.C. Roberts, The editor's roundtable: psoriasis, inflammation, and coronary artery disease, Am. J. Cardiol. 101 (2008) 1119–1126. [31] H.M. Kremers, M.T. McEvoy, F.J. Dann, S.E. Gabriel, Heart disease in psoriasis, J. Am. Acad. Dermatol. 57 (2007) 347–354. [32] Y.M. Kim, T.J. Guzik, Y.H. Zhang, M.H. Zhang, H. Kattach, C. Ratnatunga, R. Pillai, K.M. Channon, B. Casadei, A myocardial Nox2 containing NAD(P)H oxidase contributes to oxidative stress in human atrial fibrillation, Circ. Res. 97 (2005) 629–636. [33] P. Korantzopoulos, T.M. Kolettis, D. Galaris, J.A. Goudevenos, The role of oxidative stress in the pathogenesis and perpetuation of atrial fibrillation, Int. J. Cardiol. 115 (2007) 135–143. [34] T. Liu, P. Korantzopoulos, L. Li, G. Li, Preventive effects of rosuvastatin on atrial fibrillation: a meta-analysis of randomized controlled trials, Int. J. Cardiol. 167 (2013) 3058–3060. [35] T. Liu, L. Li, P. Korantzopoulos, E. Liu, G. Li, Statin use and development of atrial fibrillation: a systematic review and meta-analysis of randomized clinical trials and observational studies, Int. J. Cardiol. 126 (2008) 160–170. [36] J. Mosiewicz, A. Pietrzak, G. Chodorowska, M. Trojnar, J. Szepietowski, K. Reich, M. Rizzo, Rational for statin use in psoriatic patients, Arch. Dermatol. Res. 305 (2013) 467–472.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Psoriasis and risk of atrial fibrillation Zhiwei Zhang, Guangping Li, Tong Liu ⁎ Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China
a r t i c l e
i n f o
Article history: Received 12 March 2015 Accepted 15 March 2015 Available online 17 March 2015 Keyword: Psoriasis Atrial fibrillation Risk
Psoriasis is one of the most prevalent T-cell-mediated chronic inflammatory disorders affecting the skin, scalp, nails, and occasionally, joints. The prevalence of psoriasis in the general population ranged from 1% to 4% in population-based studies [1–3]. In recent years, several studies demonstrated that psoriasis is associated with an increased risk of cardiovascular (CV) diseases such as stroke, myocardial infarction (MI), peripheral vascular disease and CV death [4–11]. In a recently published review in the International Journal of Cardiology, Mosca et al. assessed the potential correlation between psoriasis and cardiovascular events including cerebrovascular accident, MI, thrombophlebitis, pulmonary embolism and CV mortality [12]. However, the authors did not mention the potential association between psoriasis and atrial fibrillation (AF) which is the most common sustained cardiac arrhythmia encountered in clinical practice and is associated with increased risk of morbidity and mortality [13]. We previously proposed a hypothesis on the possible relation among psoriasis, inflammation and AF [14]. In the past few years, there is increased evidence (Table 1) regarding the potential association between psoriasis and AF, and we intend to summarize the recent evidence on this issue. A Danish nationwide cohort study was first to analyze the risk of AF in the patients with psoriasis. Altogether, 36,765 patients with mild and 2793 patients with severe psoriasis were enrolled to compare with 4,478,926 subjects without psoriasis. The authors showed that in the patients with mild psoriasis, the adjusted risk ratios (RRs) for AF were 1.50 (95% CI: 1.21–1.86) in those under 50 and 1.16 (1.08–1.24) in the patients over 50 years, respectively. And in the patients with severe ⁎ Corresponding author at: Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China. E-mail address: [email protected] (T. Liu).
http://dx.doi.org/10.1016/j.ijcard.2015.03.149 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
psoriasis, a higher risk of AF was observed with RR = 2.98 (95% CI: 1.80–4.92) in those under 50 and 1.29 (95% CI: 1.01–1.65) in the patients over 50 years, suggesting that psoriasis was associated with an increased risk of AF independent of age, gender, co-morbidity, concomitant medication, and socioeconomic status. Furthermore, these also demonstrated that earlier onset psoriasis is more strongly associated with AF and the association has shown a consistent dose– response relationship between psoriasis severity and risk of AF [15]. More recently, Bang et al. [16] performed a propensity-matched analysis on 7099 hypertensive patients (154 with psoriasis) enrolled in LIFE study; they also demonstrated that psoriasis was independently associated with increased risk of new-onset AF. However, another epidemiologic study [17] reported the conflicting results from previous findings. Armstrong et al. assessed two cohorts including one cohort enrolled the patients with established cardiovascular disease (mean age N 60) and another larger cohort of out-patient psoriasis patients (mean age N 50). They suggested that there was no association between psoriasis and development of AF. In addition, they also suggested that there was no significantly increased incidence of AF for moderate-to-severe psoriasis patients as compared to the patients with mild psoriasis or the control subjects. Several pathophysiological mechanisms have been proposed as being responsible for the association linking psoriasis with AF. There is an increased interest in evaluating P-wave dispersion (PWD), which is an electrocardiographic marker related to inhomogeneous and discontinuous distribution of sinus impulse [18,19]. Besides, PWD is regarded as a marker of prolongation of intra-atrial and inter-atrial conduction time [20]. Prolonged PWD has been demonstrated to carry an increased risk for the development of AF [19,21]. Also, atrial electromechanical delay (AEMD), which shows the intra-atrial and inter-atrial conduction properties, has been associated with increased risk of AF occurrence [22, 23]. Prolongation of the duration of atrial PWD [24–27] and AEMD [24, 25] in the psoriasis patients compared with healthy controls was reported in several recently published studies. Additionally, PWD [24,27] and AEMD [25] were correlated with psoriasis area and severity index (PASI), which was used to determine the severity of psoriasis. All of these showed that atrial conduction function which may lead to AF was impaired in patients with psoriasis, and the damage was associated with the severity of psoriasis. Prolonged PWD and AEMD may due to electrophysiological and structural changes of the atrium that caused by the inflammation for the higher neutrophil to lymphocyte ratio (NLR) [24] and C-reactive protein (CRP) [25,27] levels in psoriasis patients compared with healthy controls. In addition, our previous studies have demonstrated that
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Z. Zhang et al. / International Journal of Cardiology 185 (2015) 301–303
Table 1 Summary of the three epidemiologic studies regarding AF risk in patients with psoriasis. First author (year) [ref]
Patients (n)
Study design
Endpoints
Mean or median follow-up (years)
Risk of AF
Ahlehoff et al. (2012) [15]
4,518,484 (36,765 patients with mild psoriasis; 2793 patients with severe psoriasis)
Prospective
AF; ischemic stroke
Reference population: 9.2 (mean); mild psoriasis: 5.0 (mean); severe psoriasis: 4.7 (mean)
Bang et al. (2014) [16]
7099 (154 patients with psoriasis) Prospective; randomized; double-blind
AF; HF (secondary endpoint)
4.7 ± 1.1 (mean)
Armstrong et al. (2013) [17]
507 (169 patients with psoriasis)
AF
NA
Mild Patients aged b 50 years: Adjusted psoriasis RR 1.50 (95% CI, 1.21–1.86) Patients aged ≥50 years: Adjusted RR 1.16 (95% CI, 1.08–1.24) Severe Patients aged b 50 years: Adjusted psoriasis RR 2.98 (95% CI, 1.80–4.92) Patients aged ≥ 50 years: Adjusted RR 1.29 (95% CI, 1.01–1.65) Multivariable Cox analysis: HR 1.97 (95% CI, 1.18–3.30; P = 0.010); propensity-matched analysis: OR 3.49 (95% CI, 1.24–9.81, P = 0.018) All psoriasis: 12.8 vs. 14.6% over a 10-year period, P = 0.06 Moderate-to-severe psoriasis: 11.5 vs. 12.7% over a 10-year period, P = 0.6 All psoriasis: HR 0.9 (95% CI 0.5–1.8, P = 0.8) Moderate-to-severe psoriasis: HR 2.0 (95% CI, 0.5–7.8, P = 0.3) Patients aged b 50 years: HR 0.59 (95% CI, 0.17–2.0) Patients aged ≥ 50 years: HR 1.2 (95% CI, 0.85–1.7) Mild psoriasis: adjusted HR 1.32 (95% CI, 0.91–1.89) Moderate to severe psoriasis: adjusted HR 1.27 (95% CI, 0.54–3.03)
Framingham risk score for AF
Prospective
8312 (1773 patients with mild psoriasis; 305 patients with moderate to severe psoriasis)
Prospective
2.5 (median)
AF
4.3 (mean)
AF = atrial fibrillation; HF = heart failure; RR = rate ratios; HR = hazard ratio; OR = odds ratio; CI = confidence interval; NA = not applicable.
inflammation state manifested by elevated CRP levels, was associated with a greater risk of AF [28,29]. As well as systemic inflammatory response, oxidative stress was also suggested to be one of the most important mechanisms in the development of psoriasis [30,31], and former studies have also demonstrated the possible implication of oxidative stress in increasing the AF development risk by facilitating atrial electrophysiological and structural remodeling [32,33]. Thus, inflammatory process and oxidative stress seemed to be the lines that linked psoriasis and AF. In conclusion, although the exact etiology of increased risk of AF in psoriasis patients is still not fully understood, accumulating evidence suggests that systemic inflammatory response and oxidative stress may be responsible for the increased prevalence of AF in patients with psoriasis. Whether anti-inflammatory and anti-oxidative agents have beneficial effects on the prevention of AF in the patients with psoriasis remains to be determined. Recent data have demonstrated that statins, with anti-inflammatory and anti-oxidative effects, reduce the incidence of both AF and psoriasis [34–36] which may serve as promising therapies for the prevention of AF in the patients with psoriasis.
Conflict of interest None.
Financial disclosures None.
Acknowledgments This study was partly supported by grants (30900618, 81270245 to T.L.) from the National Natural Science Foundation of China.
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