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Night shift and impaired endothelial function: Circadian out-of-synch may play a role
94
Letters to the Editor
References [1] Pelliccia A, Corrado D. The Israel screening failure analyzing the data to understand the results. J Am Coll Cardiol 2011;58:989–90. [2] Steinvil A, Chundadze T, Zeltser D, et al. Mandatory electrocardiographic screening of athletes to reduce their risk for sudden death proven fact or wishful thinking? J Am Coll Cardiol 2011;57:1291–6.
[3] Viskin S, Postema PG, Bhuiyan ZA, et al. The response of the QT interval to the brief tachycardia provoked by standing: a bedside test for diagnosing long QT syndrome. J Am Coll Cardiol 2010;55:1955–61. [4] Uberoi A, Stein R, Perez MV, et al. Interpretation of the electrocardiogram of young athletes. Circulation 2011;124:746–57. [5] Basavarajaiah S, Wilson M, Whyte G, Shah A, Behr E, Sharma S. Prevalence and significance of an isolated long QT interval in elite athletes. Eur Heart J 2007;28:2944–9.
0167-5273/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.10.034
Night shift and impaired endothelial function: Circadian out-of-synch may play a role Roberto Manfredini a,⁎, Francesco Portaluppi b a b
Section of Clinica Medica, University of Ferrara, Ferrara, Italy Hypertension Unit, Section of Clinica Medica, University of Ferrara, Ferrara, Italy
a r t i c l e
i n f o
Article history: Received 6 October 2011 Accepted 18 October 2011 Available online 5 November 2011 Keywords: Endothelial function Circadian rhythm Cardiovascular diseases
The interesting study by Kim et al. [1] reported a significant decrease in nitric oxide (NO) in a group of healthy female nurses after three sequential night shift. This study is in agreement also with a recent study by Suessenbacher et al. [2], who also demonstrated a reduced peripheral arterial tone in shift workers compared with nonshift workers. The authors state that night shift work might be a stressor capable to deteriorate flow-mediated brachial artery dilation (FMD), but the precise mechanism is unknown. On one hand, the existence of a circadian variation in basal vascular tone, due at least in part to increased alpha-sympathetic vasoconstrictor activity, has been demonstrated [3], and this could play a role in the complex series of triggering factors potentially favoring the higher incidence of acute cardiac ischemic events in the morning [4]. On the other hand, a recent growing body of evidence has shown that vascular function and circadian clocks are tightly coupled [4]. Circadian clocks exist as a selfsustained transcriptional-translational circuit consisting of positive and negative feedback loops, and generating a rhythm in gene expression with a period of approximately 24 hours [4]. The principal (master) circadian clock is located in the suprachiasmatic nucleus of the hypothalamus and is entrained by light, but peripheral circadian clocks have been identified within almost all mammalian cell types, including cardiomyocytes, vascular smooth muscle cells, and endothelial cells [5]. The principal role of cellular biological clocks is driving circadian rhythms to adapt the organism to further needs in an anticipatory manner, so providing selective advantage [6]. However, it has been recently shown that external or internal disruption (dyssinchrony) of circadian control may result in overt diseases. For example, mice exposed to a 20-hour instead of 24-hour circadian rhythm show a complete disruption of sleep/wake behavior and a marked progression of myocyte hypertrophy and fibrosis [7]. Again, bmal1 knockout mice or
⁎ Corresponding author at: Section of Clinica Medica, Department of Clinical and Experimental Medicine, University of Ferrara, via Savonarola 9, 44100 Ferrara, Italy. Tel.: +39 0532 237166; fax: + 39 0532 236816. E-mail address: [email protected] (R. Manfredini).
clock mutant mice exhibit impairment of normal protective endothelial responses to vascular injury with pathological remodeling and predisposition to vascular thrombosis [8], and mice with mutation in the Per2 gene show endothelial disfunction characterized by decreased production of NO and vasodilatory prostaglandins, and increased release of cyclooxygenase-1-derived vasoconstrictor substances [9]. Thus, it is quite likely that vascular and endothelial function and NO production may be affected and impaired in night shift workers via a circadian-based mechanism. Now, we have no conclusive data on whether out-of-synch of biological clocks may influence health or disease, and which amount of circadian rhythm disruption or sleep deprivation may be harmful for the cardiovascular system. For example, it has been found that the incidence of acute myocardial infarction was slightly (but significantly) increased for the first three weekdays after the transition to daylight saving time in the spring, with an incidence ratio of 1.051 for the first week [10]. Finally, several risk factors have to be considered when evaluating shift work disorder, e.g., age, female sex, time of light exposure, duration of the shift, familial (genetic) predisposition, and so on [11]. The results reported by Kim et al. [1] have been obtained after a sequential series of three night shifts, and rapid shift rotation is suggested to not allow bodily's rhythms to synchronize to a new schedule. In conclusion, keeping away from alarmistic manipulations, it is undoubtful that circadian rhythms play an important role in cardiovascular health and disease, and further studies on night shiftworkers should be addressed to clarify potential cardiovascular effects of possible rhythm disruption. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Shewan and Coats 2010:144:1–2). References [1] Kim W, Park HH, Park CS, et al. Impaired endothelial function in medical personnel working sequential night shifts. Int J Cardiol 2011;151:377–8. [2] Suessenbacher A, Potocnik M, Dorler J, et al. Comparison of peripheral endothelial function in shift versus nonshift workers. Am J Cardiol 2011;107:945–8. [3] Panza JA, Epstein SE, Quyyumi AA. Circadian variation in vascular tone and its relation to alpha-sympathetic vasoconstrictor activity. N Engl J Med 1991;325:986–90. [4] Manfredini R, Boari B, Bressan S, et al. Influence of circadian rhythm on mortality after myocardial infarction: data from a prospective cohort of emergency calls. Am J Emerg Med 2004;22:555–9. [5] Martino TA, Sole MJ. Molecular time. An ofter overlooked dimension to cardiovascular disease. Circ Res 2009;105:1047–61. [6] Paschos GK, FitzGerald GA. Circadian clocks and vascular function. Circ Res 2010;106:833–41. [7] Martino TA, Tata N, Belsham DD, et al. Disturbed diurnal rhythm alter gene expression and exacerbates cardiovascular disease with rescue by resynchronization. Hypertension 2007;49:1104–13.
Letters to the Editor [8] Anea CB, Zhang M, Stepp DW, et al. Vascular disease in mice with a dysfunctional circadian clock. Circulation 2009;119:1510–7. [9] Viswambharan H, Carvas JM, Antic V, et al. Mutation of the circadian clock gene Per2 alters vascular endothelial function. Circulation 2007;115:2188–95.
0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.10.029
95
[10] Janszky I, Ljung R. Shifts to and from daylight saving time and incidence of myocardial infarction. N Engl J Med 2008;359:1966–9. [11] Sack RL, Auckley D, Auger R, et al. Circadian rhythm sleep disorders: Part I, basic principles, shift work and jet lag disorders. Sleep 2007;30:1460–83.
Letters to the Editor
References [1] Pelliccia A, Corrado D. The Israel screening failure analyzing the data to understand the results. J Am Coll Cardiol 2011;58:989–90. [2] Steinvil A, Chundadze T, Zeltser D, et al. Mandatory electrocardiographic screening of athletes to reduce their risk for sudden death proven fact or wishful thinking? J Am Coll Cardiol 2011;57:1291–6.
[3] Viskin S, Postema PG, Bhuiyan ZA, et al. The response of the QT interval to the brief tachycardia provoked by standing: a bedside test for diagnosing long QT syndrome. J Am Coll Cardiol 2010;55:1955–61. [4] Uberoi A, Stein R, Perez MV, et al. Interpretation of the electrocardiogram of young athletes. Circulation 2011;124:746–57. [5] Basavarajaiah S, Wilson M, Whyte G, Shah A, Behr E, Sharma S. Prevalence and significance of an isolated long QT interval in elite athletes. Eur Heart J 2007;28:2944–9.
0167-5273/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.10.034
Night shift and impaired endothelial function: Circadian out-of-synch may play a role Roberto Manfredini a,⁎, Francesco Portaluppi b a b
Section of Clinica Medica, University of Ferrara, Ferrara, Italy Hypertension Unit, Section of Clinica Medica, University of Ferrara, Ferrara, Italy
a r t i c l e
i n f o
Article history: Received 6 October 2011 Accepted 18 October 2011 Available online 5 November 2011 Keywords: Endothelial function Circadian rhythm Cardiovascular diseases
The interesting study by Kim et al. [1] reported a significant decrease in nitric oxide (NO) in a group of healthy female nurses after three sequential night shift. This study is in agreement also with a recent study by Suessenbacher et al. [2], who also demonstrated a reduced peripheral arterial tone in shift workers compared with nonshift workers. The authors state that night shift work might be a stressor capable to deteriorate flow-mediated brachial artery dilation (FMD), but the precise mechanism is unknown. On one hand, the existence of a circadian variation in basal vascular tone, due at least in part to increased alpha-sympathetic vasoconstrictor activity, has been demonstrated [3], and this could play a role in the complex series of triggering factors potentially favoring the higher incidence of acute cardiac ischemic events in the morning [4]. On the other hand, a recent growing body of evidence has shown that vascular function and circadian clocks are tightly coupled [4]. Circadian clocks exist as a selfsustained transcriptional-translational circuit consisting of positive and negative feedback loops, and generating a rhythm in gene expression with a period of approximately 24 hours [4]. The principal (master) circadian clock is located in the suprachiasmatic nucleus of the hypothalamus and is entrained by light, but peripheral circadian clocks have been identified within almost all mammalian cell types, including cardiomyocytes, vascular smooth muscle cells, and endothelial cells [5]. The principal role of cellular biological clocks is driving circadian rhythms to adapt the organism to further needs in an anticipatory manner, so providing selective advantage [6]. However, it has been recently shown that external or internal disruption (dyssinchrony) of circadian control may result in overt diseases. For example, mice exposed to a 20-hour instead of 24-hour circadian rhythm show a complete disruption of sleep/wake behavior and a marked progression of myocyte hypertrophy and fibrosis [7]. Again, bmal1 knockout mice or
⁎ Corresponding author at: Section of Clinica Medica, Department of Clinical and Experimental Medicine, University of Ferrara, via Savonarola 9, 44100 Ferrara, Italy. Tel.: +39 0532 237166; fax: + 39 0532 236816. E-mail address: [email protected] (R. Manfredini).
clock mutant mice exhibit impairment of normal protective endothelial responses to vascular injury with pathological remodeling and predisposition to vascular thrombosis [8], and mice with mutation in the Per2 gene show endothelial disfunction characterized by decreased production of NO and vasodilatory prostaglandins, and increased release of cyclooxygenase-1-derived vasoconstrictor substances [9]. Thus, it is quite likely that vascular and endothelial function and NO production may be affected and impaired in night shift workers via a circadian-based mechanism. Now, we have no conclusive data on whether out-of-synch of biological clocks may influence health or disease, and which amount of circadian rhythm disruption or sleep deprivation may be harmful for the cardiovascular system. For example, it has been found that the incidence of acute myocardial infarction was slightly (but significantly) increased for the first three weekdays after the transition to daylight saving time in the spring, with an incidence ratio of 1.051 for the first week [10]. Finally, several risk factors have to be considered when evaluating shift work disorder, e.g., age, female sex, time of light exposure, duration of the shift, familial (genetic) predisposition, and so on [11]. The results reported by Kim et al. [1] have been obtained after a sequential series of three night shifts, and rapid shift rotation is suggested to not allow bodily's rhythms to synchronize to a new schedule. In conclusion, keeping away from alarmistic manipulations, it is undoubtful that circadian rhythms play an important role in cardiovascular health and disease, and further studies on night shiftworkers should be addressed to clarify potential cardiovascular effects of possible rhythm disruption. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Shewan and Coats 2010:144:1–2). References [1] Kim W, Park HH, Park CS, et al. Impaired endothelial function in medical personnel working sequential night shifts. Int J Cardiol 2011;151:377–8. [2] Suessenbacher A, Potocnik M, Dorler J, et al. Comparison of peripheral endothelial function in shift versus nonshift workers. Am J Cardiol 2011;107:945–8. [3] Panza JA, Epstein SE, Quyyumi AA. Circadian variation in vascular tone and its relation to alpha-sympathetic vasoconstrictor activity. N Engl J Med 1991;325:986–90. [4] Manfredini R, Boari B, Bressan S, et al. Influence of circadian rhythm on mortality after myocardial infarction: data from a prospective cohort of emergency calls. Am J Emerg Med 2004;22:555–9. [5] Martino TA, Sole MJ. Molecular time. An ofter overlooked dimension to cardiovascular disease. Circ Res 2009;105:1047–61. [6] Paschos GK, FitzGerald GA. Circadian clocks and vascular function. Circ Res 2010;106:833–41. [7] Martino TA, Tata N, Belsham DD, et al. Disturbed diurnal rhythm alter gene expression and exacerbates cardiovascular disease with rescue by resynchronization. Hypertension 2007;49:1104–13.
Letters to the Editor [8] Anea CB, Zhang M, Stepp DW, et al. Vascular disease in mice with a dysfunctional circadian clock. Circulation 2009;119:1510–7. [9] Viswambharan H, Carvas JM, Antic V, et al. Mutation of the circadian clock gene Per2 alters vascular endothelial function. Circulation 2007;115:2188–95.
0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.10.029
95
[10] Janszky I, Ljung R. Shifts to and from daylight saving time and incidence of myocardial infarction. N Engl J Med 2008;359:1966–9. [11] Sack RL, Auckley D, Auger R, et al. Circadian rhythm sleep disorders: Part I, basic principles, shift work and jet lag disorders. Sleep 2007;30:1460–83.