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C-reactive protein and oxidative stress in atrial fibrillation
International Journal of Cardiology 88 (2003) 103–104 www.elsevier.com / locate / ijcard
Letter to the Editor
C-reactive protein and oxidative stress in atrial fibrillation Panagiotis Korantzopoulos a
a,b ,
*, Dimitrios Galaris a , Dimitrios Papaioannides b , Stelianos Kokkoris a
Laboratory of Biological Chemistry, Medical School, University of Ioannina, 45110 Ioannina, Greece b Department of Medicine, Arta General District Hospital, 47100 Arta, Greece Received 16 February 2002; accepted 6 April 2002
Keywords: C-reactive protein; Oxidative stress; Atrial fibrillation
Atrial fibrillation (AF) represents the most frequent sustained arrhythmia encountered in clinical practice [1]. Structural and electrophysiological remodeling is being widely recognized as a critical process in the pathophysiology of this disorder. Although the exact underlying molecular mechanism(s) remain unknown, calcium overload seems to contribute considerably to these changes [1]. Accumulating evidence supports the role of oxidative stress in cardiac dysfunction under a wide variety of pathophysiological conditions [2,3]. Recently, oxidative stress was found to be substantially involved in the above-mentioned remodeling during AF [4,5]. In particular, ascorbate (vitamin C), an outstanding water-soluble antioxidant, was shown to ameliorate electrophysiological remodeling and reduce the occurrence of postoperative AF, possibly through scavenging of peroxynitrite [5] and other reactive oxygen species [6]. These toxic molecules may promote oxidative modification of myofibrillar proteins as well as other essential cellular components in atrial myocytes [4]. Furthermore, it is established that oxidative stress can promote calcium overload in myocardial stunning [2] and reduce nitric oxide bioavailability in endothelial dysfunction [3]. *Corresponding author. Laboratory of Biological Chemistry, University of Ioannina, Medical School, 45110 Ioannina, Greece. Tel.: 130-651097562; fax: 130-6510-67868. E-mail address: [email protected] (P. Korantzopoulos).
The impact of these phenomena in AF remains to be elucidated [7]. On the other hand, it has been proposed that inflammatory processes may contribute to atrial remodeling and promote AF persistence. C-reactive protein (CRP), a classic inflammatory marker, is strongly associated with the risk for major cardiovascular events, representing the total inflammatory burden in atherosclerotic disease [8]. Currently, a novel fascinating association between AF and CRP was emerged. Two independent clinical trials that appeared simultaneously showed that CRP is significantly elevated in AF patients [9,10]. The elevation was significantly greater in individuals suffering from persistent AF than those from paroxysmal AF. In addition, CRP proposed to be a determinant of efficient cardioversion of paroxysmal AF in sinus rhythm [10]. Despite the uncertainty whether CRP elevation is the cause or consequence of AF, the potential clinical applications of this inflammatory marker are promising. Compelling evidence is accumulating that inflammation is associated with antioxidant status [11], giving rise to the assumption that CRP may correlate with oxidative stress observed in AF. It seems reasonable that antioxidant interventions may decrease CRP levels and exert favorable effects on atrial remodeling. Langlois et al. [12] demonstrated a negative association between ascorbate and CRP
0167-5273 / 02 / $ – see front matter 2002 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S0167-5273(02)00386-8
104
P. Korantzopoulos et al. / International Journal of Cardiology 88 (2003) 103–104
related to the severity of atherosclerosis in peripheral arterial disease. Equivalent data regarding AF is lacking, but under the light of current investigations positive results in the near future are highly possible. In conclusion, CRP may become a useful marker in the evaluation of antioxidant interventions in AF. Besides pure antioxidants, various cardiovascular drugs exhibit antioxidant and / or anti-inflammatory capacity. Thus, medications such as ascorbate, statins, aspirin, and trimetazidine deserve further evaluation in AF patients [5,8,13]. It remains to be seen whether this pioneering idea can be put into clinical practice.
References [1] Jahangir A, Munger TM, Packer DL, Crijns HJGM. Atrial fibrillation. In: Podrid PJ, Kowey PR, editors, Cardiac arrhythmia: mechanisms, diagnosis, and management, 2nd ed., Philadelphia, PA: Lippincott Williams & Wilkins, 2001, pp. 457–99. [2] Dhalla NS, Temsah RM, Netticadan T. Role of oxidative stress in cardiovascular diseases. J Hypertens 2000;18:655–73. [3] Korantzopoulos P, Galaris D. The protective role of vitamin C on endothelial dysfunction. J Clin Basic Cardiol, in press. [4] Mihm MJ, Yu F, Carnes CA et al. Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation. Circulation 2001;104:174–80.
[5] Carnes CA, Chung MK, Nakayama T et al. Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation. Circ Res 2001;89:e32–8. [6] Galaris D, Korantzopoulos P. On the molecular mechanism of metmyoglobin-catalyzed reduction of hydrogen peroxide by ascorbate. Free Radic Biol Med 1997;22:657–67. [7] Minamino T, Kitakaze M, Sato H et al. Plasma levels of nitrite / nitrate and platelet cGMP levels are decreased in patients with atrial fibrillation. Arterioscler Thromb Vasc Biol 1997;17:3191–5. [8] de Ferranti S, Rifai N. C-reactive protein and cardiovascular disease: a review of risk prediction and interventions. Clin Chim Acta 2002;317:1–15. [9] Chung MK, Martin DO, Sprecher D et al. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation 2001;104:2886–91. [10] Dernellis J, Panaretou M. C-reactive protein and paroxysmal atrial fibrillation: evidence of the implication of an inflammatory process in paroxysmal atrial fibrillation. Acta Cardiol 2001;56:375–80. [11] Halliwell B, Gutteridge JMC. Free radicals in biology and medicine, 3rd ed.. Oxford: Oxford University Press, 1999. [12] Langlois M, Duprez D, Delanghe J, DeBuyzere M, Clement DL. Serum vitamin C concentration is low in peripheral arterial disease and is associated with inflammation and severity of atherosclerosis. Circulation 2001;103:1863–8. [13] Tselepis A, Doulias P-T, Lourida E, Glantzounis G, Tsimoyiannis E, Galaris D. Trimetazidine protects low-density lipoproteins from oxidation and cultured cells exposed to H 2 O 2 from DNA damage. Free Radic Biol Med 2001;30:1357–64.
Letter to the Editor
C-reactive protein and oxidative stress in atrial fibrillation Panagiotis Korantzopoulos a
a,b ,
*, Dimitrios Galaris a , Dimitrios Papaioannides b , Stelianos Kokkoris a
Laboratory of Biological Chemistry, Medical School, University of Ioannina, 45110 Ioannina, Greece b Department of Medicine, Arta General District Hospital, 47100 Arta, Greece Received 16 February 2002; accepted 6 April 2002
Keywords: C-reactive protein; Oxidative stress; Atrial fibrillation
Atrial fibrillation (AF) represents the most frequent sustained arrhythmia encountered in clinical practice [1]. Structural and electrophysiological remodeling is being widely recognized as a critical process in the pathophysiology of this disorder. Although the exact underlying molecular mechanism(s) remain unknown, calcium overload seems to contribute considerably to these changes [1]. Accumulating evidence supports the role of oxidative stress in cardiac dysfunction under a wide variety of pathophysiological conditions [2,3]. Recently, oxidative stress was found to be substantially involved in the above-mentioned remodeling during AF [4,5]. In particular, ascorbate (vitamin C), an outstanding water-soluble antioxidant, was shown to ameliorate electrophysiological remodeling and reduce the occurrence of postoperative AF, possibly through scavenging of peroxynitrite [5] and other reactive oxygen species [6]. These toxic molecules may promote oxidative modification of myofibrillar proteins as well as other essential cellular components in atrial myocytes [4]. Furthermore, it is established that oxidative stress can promote calcium overload in myocardial stunning [2] and reduce nitric oxide bioavailability in endothelial dysfunction [3]. *Corresponding author. Laboratory of Biological Chemistry, University of Ioannina, Medical School, 45110 Ioannina, Greece. Tel.: 130-651097562; fax: 130-6510-67868. E-mail address: [email protected] (P. Korantzopoulos).
The impact of these phenomena in AF remains to be elucidated [7]. On the other hand, it has been proposed that inflammatory processes may contribute to atrial remodeling and promote AF persistence. C-reactive protein (CRP), a classic inflammatory marker, is strongly associated with the risk for major cardiovascular events, representing the total inflammatory burden in atherosclerotic disease [8]. Currently, a novel fascinating association between AF and CRP was emerged. Two independent clinical trials that appeared simultaneously showed that CRP is significantly elevated in AF patients [9,10]. The elevation was significantly greater in individuals suffering from persistent AF than those from paroxysmal AF. In addition, CRP proposed to be a determinant of efficient cardioversion of paroxysmal AF in sinus rhythm [10]. Despite the uncertainty whether CRP elevation is the cause or consequence of AF, the potential clinical applications of this inflammatory marker are promising. Compelling evidence is accumulating that inflammation is associated with antioxidant status [11], giving rise to the assumption that CRP may correlate with oxidative stress observed in AF. It seems reasonable that antioxidant interventions may decrease CRP levels and exert favorable effects on atrial remodeling. Langlois et al. [12] demonstrated a negative association between ascorbate and CRP
0167-5273 / 02 / $ – see front matter 2002 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S0167-5273(02)00386-8
104
P. Korantzopoulos et al. / International Journal of Cardiology 88 (2003) 103–104
related to the severity of atherosclerosis in peripheral arterial disease. Equivalent data regarding AF is lacking, but under the light of current investigations positive results in the near future are highly possible. In conclusion, CRP may become a useful marker in the evaluation of antioxidant interventions in AF. Besides pure antioxidants, various cardiovascular drugs exhibit antioxidant and / or anti-inflammatory capacity. Thus, medications such as ascorbate, statins, aspirin, and trimetazidine deserve further evaluation in AF patients [5,8,13]. It remains to be seen whether this pioneering idea can be put into clinical practice.
References [1] Jahangir A, Munger TM, Packer DL, Crijns HJGM. Atrial fibrillation. In: Podrid PJ, Kowey PR, editors, Cardiac arrhythmia: mechanisms, diagnosis, and management, 2nd ed., Philadelphia, PA: Lippincott Williams & Wilkins, 2001, pp. 457–99. [2] Dhalla NS, Temsah RM, Netticadan T. Role of oxidative stress in cardiovascular diseases. J Hypertens 2000;18:655–73. [3] Korantzopoulos P, Galaris D. The protective role of vitamin C on endothelial dysfunction. J Clin Basic Cardiol, in press. [4] Mihm MJ, Yu F, Carnes CA et al. Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation. Circulation 2001;104:174–80.
[5] Carnes CA, Chung MK, Nakayama T et al. Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation. Circ Res 2001;89:e32–8. [6] Galaris D, Korantzopoulos P. On the molecular mechanism of metmyoglobin-catalyzed reduction of hydrogen peroxide by ascorbate. Free Radic Biol Med 1997;22:657–67. [7] Minamino T, Kitakaze M, Sato H et al. Plasma levels of nitrite / nitrate and platelet cGMP levels are decreased in patients with atrial fibrillation. Arterioscler Thromb Vasc Biol 1997;17:3191–5. [8] de Ferranti S, Rifai N. C-reactive protein and cardiovascular disease: a review of risk prediction and interventions. Clin Chim Acta 2002;317:1–15. [9] Chung MK, Martin DO, Sprecher D et al. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation 2001;104:2886–91. [10] Dernellis J, Panaretou M. C-reactive protein and paroxysmal atrial fibrillation: evidence of the implication of an inflammatory process in paroxysmal atrial fibrillation. Acta Cardiol 2001;56:375–80. [11] Halliwell B, Gutteridge JMC. Free radicals in biology and medicine, 3rd ed.. Oxford: Oxford University Press, 1999. [12] Langlois M, Duprez D, Delanghe J, DeBuyzere M, Clement DL. Serum vitamin C concentration is low in peripheral arterial disease and is associated with inflammation and severity of atherosclerosis. Circulation 2001;103:1863–8. [13] Tselepis A, Doulias P-T, Lourida E, Glantzounis G, Tsimoyiannis E, Galaris D. Trimetazidine protects low-density lipoproteins from oxidation and cultured cells exposed to H 2 O 2 from DNA damage. Free Radic Biol Med 2001;30:1357–64.