Sleep Medicine 16 (2015) 435–436
Contents lists available at ScienceDirect
Sleep Medicine j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / s l e e p
Editorial
Circadian rhythm complexities in cardiovascular dynamics
Circadian rhythms are externally entrainable, centrally integrated, and endogenously communicated and synchronized biological processes, which govern physiologic functions according to a roughly 24-hour cycle. Circadian clock genes which administrate these rhythms are found in nearly all cells of most organisms, and statistical evidence clearly demonstrates a correlation between the incidence and severity of many disease processes with disruption of the circadian clock regulatory mechanisms. For example, changes that occur in response to alterations in light–dark cycles can adversely influence normal physiology, as evidenced by increased incidence of cardiovascular and hemodynamic events in the morning hours and in shift workers. Additionally, the time-of-day at which the compensatory response to a pathologic situation occurs and a treatment is applied can influence the degree of severity of the condition as well as the long-term outcome, demonstrating the potential utility of circadian rhythm management as a prognostic and therapeutic tool [1–7]. Fluctuations in cardiovascular function during the 24-hour cycle occur relative to the demands on the heart. For example, the transition from sleep to wake requires the heart to adjust from a period of low to high activity. A diurnal pattern in the incidence of acute myocardial infarction (MI) has been consistently shown to occur, and changes in arterial blood pressure, hypercoaguability, hormonal fluctuations, increased oxygen demand of the heart, increased vascular/sympathetic tone, and electrical instability are, either alone or combined, potentially culpable [8–10]. Some investigators propose that circadian variations are dependent upon neurohumoral or autonomic control and that these determine onset of acute cardiac events. However, the timing for these centrally-mediated occurrences does not necessarily align with the pathological happenings. In order to better understand and prevent myocardial injury due to perturbations in circadian rhythms, the molecular clock mechanisms in the heart and their role in controlling metabolism and determining the adaptive response to stress and disease are being actively investigated. In pursuit of a noninvasive intervention aimed at reducing the incidence of cardiac events, the work by Dr. Viola et al., “Dawn Simulation Light: A Potential Cardiac Events Protector” in this issue of Sleep Medicine, describes their experiments controlling light exposure in healthy young men to reduce sleep-to-wake changes in heart rate due to deleterious fluctuations in excitation that increase vulnerability to potential cardiac injury. They conclude that dawn simulation encompassing the wake-up time resulted in dampening of the heart rate and autonomic modulation, thus improving cardiac stability. Electrocardiogram (ECG) recordings, salivary cortisol, and methods for measuring sympathetic and vagal modulation are http://dx.doi.org/10.1016/j.sleep.2015.01.014 1389-9457/© 2015 Elsevier B.V. All rights reserved.
accepted means by which the degree of stress incurred during the transition from sleep to wake can be assessed. These measures have been recorded in similar experiments by these authors and others, demonstrating the effects of light exposure during waking to influence mood, alertness, and cognition [11–15]. However, given the inconclusiveness of the salivary cortisol measure (cortisol and the sympathetic nervous system [SNS] are known to increase upon awakening but a direct relationship between cortisol and cardiac autonomic activity have not been firmly established) [16,17], corroboration by other non-invasive measures such as systemic hormone levels (leptin, insulin), cytokine production, leukocyte numbers and distribution, echocardiography, electroencephalogram (performed on these subjects in a separate publication by Gabel et al. [18]) to fully characterize the correlation of sleep phase with the cardiac function changes, and melatonin (which they have measured in a previous study with a similar design to assess the effects of dawn simulation on cognitive performance) may have helped substantiate their findings [19]. Further, given that these are healthy young men without sleep pattern abnormalities, to the exclusion of women, aged, as well as ethnic and weight differences, the relevance to the population at risk is questionable. Since they found that differences in cognitive function and mood, and light intensity and seasonal changes have variable effects on the neuroendocrine and central nervous system function [20], it seems as though a description of differences in spectral sensitivity and brightness perception of subjects’ vision would also be valuable. While the notion of identifying a noninvasive and minimally imposing strategy to reduce the most prominently known stressor for initiating an acute coronary event is a laudable goal, the deficiency in mechanistic evidence to conclusively correlate their findings with a reduction in onset of acute MI leaves the reader uncertain about the degree to which this dawn simulation actually disrupts the circadian clock mechanism and whether it would be effective in susceptible populations. More data are required to draw stronger correlative deductions with respect to known clock mediators and alterations in systemic factors driven by circadian misalignment. Ideally, work of this nature supported by further studies in experimental models including ongoing disease processes (eg, hypertension, obesity, diabetes) would help to establish a rationale for further investigation of the potential for chronotherapy.
Conflict of interest The author reports no conflict of interest. The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: http://dx.doi.org/10.1016/j.sleep.2015.01.014.
436
Editorial/Sleep Medicine 16 (2015) 435–436
References [1] Virag JA, Lust RM. Circadian influences on myocardial infarction. Front Physiol 2014;5:422. doi:10.3389/fphys.2014.00422. PubMed PMID: 25400588, PMCID: 4214187. [2] Arendt J. Shift work: coping with the biological clock. Occup Med (Lond) 2010;60(1):10–20. doi:10.1093/occmed/kqp162. [Epub 2010/01/07]. PubMed PMID: 20051441. [3] Muller JE. Circadian variation in cardiovascular events. Am J Hypertens 1999;12(2 Pt 2):35S–42S. PubMed PMID: 10090293. [4] Smolensky MH, Portaluppi F. Chronopharmacology and chronotherapy of cardiovascular medications: relevance to prevention and treatment of coronary heart disease. Am Heart J 1999;137(4 Pt 2):S14–24. doi:a96908. [Epub 1999/ 03/31]. PubMed PMID: 10097242. [5] Fujino Y, Iso H, Tamakoshi A, et al. A prospective cohort study of shift work and risk of ischemic heart disease in Japanese male workers. Am J Epidemiol 2006;164(2):128–35. PubMed PMID: 16707650. [6] Mosendane T, Raal FJ. Shift work and its effects on the cardiovascular system. Cardiovasc J Afr 2008;19(4):210–15. [Epub 2008/09/09]. PubMed PMID: 18776968. [7] Scheer FA, Hilton MF, Mantzoros CS, et al. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci USA 2009;106(11):4453–8. doi:10.1073/pnas.0808180106. [Epub 2009/03/04]. PubMed PMID: 19255424, PMCID: 2657421. [8] Muller JE. Circadian variation and triggering of acute coronary events. Am Heart J 1999;137(4 Pt 2):S1–8. PubMed PMID: 10097240. [9] Li JJ. Circadian variation in myocardial ischemia: the possible mechanisms involving in this phenomenon. Med Hypotheses 2003;61(2):240–3. PubMed PMID: 12888312. [10] Boudreau P, Yeh WH, Dumont GA, et al. A circadian rhythm in heart rate variability contributes to the increased cardiac sympathovagal response to awakening in the morning. Chronobiol Int 2012;29(6):757–68. doi:10.3109/ 07420528.2012.674592. PubMed PMID: 22734576. [11] Gabel V, Maire M, Reichert CF, et al. Effects of artificial dawn and morning blue light on daytime cognitive performance, well-being, cortisol and melatonin levels. Chronobiol Int 2013;30(8):988–97. doi:10.3109/07420528.2013.793196. PubMed PMID: 23841684. [12] Lafrance C, Dumont M, Lesperance P, et al. Daytime vigilance after morning bright light exposure in volunteers subjected to sleep restriction. Physiol Behav 1998;63(5):803–10. PubMed PMID: 9618002.
[13] Munch M, Linhart F, Borisuit A, et al. Effects of prior light exposure on early evening performance, subjective sleepiness, and hormonal secretion. Behav Neurosci 2012;126(1):196–203. doi:10.1037/a0026702. PubMed PMID: 22201280. [14] Leichtfried V, Mair-Raggautz M, Schaeffer V, et al. Intense illumination in the morning hours improved mood and alertness but not mental performance. Appl Ergon 2015;46(Pt A):54–9. doi:10.1016/j.apergo.2014.07.001. PubMed PMID: 25106786. [15] Smolders KC, de Kort YA, Cluitmans PJ. A higher illuminance induces alertness even during office hours: findings on subjective measures, task performance and heart rate measures. Physiol Behav 2012;107(1):7–16. doi:10.1016/ j.physbeh.2012.04.028. PubMed PMID: 22564492. [16] Clow A, Thorn L, Evans P, et al. The awakening cortisol response: methodological issues and significance. Stress 2004;7(1):29–37. doi:10.1080/ 10253890410001667205. PubMed PMID: 15204030. [17] Thorn L, Hucklebridge F, Esgate A, et al. The effect of dawn simulation on the cortisol response to awakening in healthy participants. Psychoneuroendocrinology 2004;29(7):925–30. doi:10.1016/j.psyneuen.2003.08.005. PubMed PMID: 15177708. [18] Gabel V, Maire M, Reichert CF, et al. Dawn simulation light impacts on different cognitive domains under sleep restriction. Behav Brain Res 2014;281C:258–66. doi:10.1016/j.bbr.2014.12.043. PubMed PMID: 25549858. [19] Singh RB, Kartik C, Otsuka K, et al. Brain-heart connection and the risk of heart attack. Biomed Pharmacother 2002;56(Suppl. 2):257s–65s. PubMed PMID: 12653178. [20] Wehr TA. Effect of seasonal changes in daylength on human neuroendocrine function. Horm Res 1998;49(3–4):118–24. PubMed PMID: 9550111.
Jitka A.I. Virag * Department of Physiology, Brody School of Medicine, East Carolina University, 600 Moye Blvd, Greenville, NC 6N-98, USA * Tel.: +1 252 744 2777; fax: +1 252 744 5477. E-mail address: [email protected] Available online 26 January 2015
Contents lists available at ScienceDirect
Sleep Medicine j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / s l e e p
Editorial
Circadian rhythm complexities in cardiovascular dynamics
Circadian rhythms are externally entrainable, centrally integrated, and endogenously communicated and synchronized biological processes, which govern physiologic functions according to a roughly 24-hour cycle. Circadian clock genes which administrate these rhythms are found in nearly all cells of most organisms, and statistical evidence clearly demonstrates a correlation between the incidence and severity of many disease processes with disruption of the circadian clock regulatory mechanisms. For example, changes that occur in response to alterations in light–dark cycles can adversely influence normal physiology, as evidenced by increased incidence of cardiovascular and hemodynamic events in the morning hours and in shift workers. Additionally, the time-of-day at which the compensatory response to a pathologic situation occurs and a treatment is applied can influence the degree of severity of the condition as well as the long-term outcome, demonstrating the potential utility of circadian rhythm management as a prognostic and therapeutic tool [1–7]. Fluctuations in cardiovascular function during the 24-hour cycle occur relative to the demands on the heart. For example, the transition from sleep to wake requires the heart to adjust from a period of low to high activity. A diurnal pattern in the incidence of acute myocardial infarction (MI) has been consistently shown to occur, and changes in arterial blood pressure, hypercoaguability, hormonal fluctuations, increased oxygen demand of the heart, increased vascular/sympathetic tone, and electrical instability are, either alone or combined, potentially culpable [8–10]. Some investigators propose that circadian variations are dependent upon neurohumoral or autonomic control and that these determine onset of acute cardiac events. However, the timing for these centrally-mediated occurrences does not necessarily align with the pathological happenings. In order to better understand and prevent myocardial injury due to perturbations in circadian rhythms, the molecular clock mechanisms in the heart and their role in controlling metabolism and determining the adaptive response to stress and disease are being actively investigated. In pursuit of a noninvasive intervention aimed at reducing the incidence of cardiac events, the work by Dr. Viola et al., “Dawn Simulation Light: A Potential Cardiac Events Protector” in this issue of Sleep Medicine, describes their experiments controlling light exposure in healthy young men to reduce sleep-to-wake changes in heart rate due to deleterious fluctuations in excitation that increase vulnerability to potential cardiac injury. They conclude that dawn simulation encompassing the wake-up time resulted in dampening of the heart rate and autonomic modulation, thus improving cardiac stability. Electrocardiogram (ECG) recordings, salivary cortisol, and methods for measuring sympathetic and vagal modulation are http://dx.doi.org/10.1016/j.sleep.2015.01.014 1389-9457/© 2015 Elsevier B.V. All rights reserved.
accepted means by which the degree of stress incurred during the transition from sleep to wake can be assessed. These measures have been recorded in similar experiments by these authors and others, demonstrating the effects of light exposure during waking to influence mood, alertness, and cognition [11–15]. However, given the inconclusiveness of the salivary cortisol measure (cortisol and the sympathetic nervous system [SNS] are known to increase upon awakening but a direct relationship between cortisol and cardiac autonomic activity have not been firmly established) [16,17], corroboration by other non-invasive measures such as systemic hormone levels (leptin, insulin), cytokine production, leukocyte numbers and distribution, echocardiography, electroencephalogram (performed on these subjects in a separate publication by Gabel et al. [18]) to fully characterize the correlation of sleep phase with the cardiac function changes, and melatonin (which they have measured in a previous study with a similar design to assess the effects of dawn simulation on cognitive performance) may have helped substantiate their findings [19]. Further, given that these are healthy young men without sleep pattern abnormalities, to the exclusion of women, aged, as well as ethnic and weight differences, the relevance to the population at risk is questionable. Since they found that differences in cognitive function and mood, and light intensity and seasonal changes have variable effects on the neuroendocrine and central nervous system function [20], it seems as though a description of differences in spectral sensitivity and brightness perception of subjects’ vision would also be valuable. While the notion of identifying a noninvasive and minimally imposing strategy to reduce the most prominently known stressor for initiating an acute coronary event is a laudable goal, the deficiency in mechanistic evidence to conclusively correlate their findings with a reduction in onset of acute MI leaves the reader uncertain about the degree to which this dawn simulation actually disrupts the circadian clock mechanism and whether it would be effective in susceptible populations. More data are required to draw stronger correlative deductions with respect to known clock mediators and alterations in systemic factors driven by circadian misalignment. Ideally, work of this nature supported by further studies in experimental models including ongoing disease processes (eg, hypertension, obesity, diabetes) would help to establish a rationale for further investigation of the potential for chronotherapy.
Conflict of interest The author reports no conflict of interest. The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: http://dx.doi.org/10.1016/j.sleep.2015.01.014.
436
Editorial/Sleep Medicine 16 (2015) 435–436
References [1] Virag JA, Lust RM. Circadian influences on myocardial infarction. Front Physiol 2014;5:422. doi:10.3389/fphys.2014.00422. PubMed PMID: 25400588, PMCID: 4214187. [2] Arendt J. Shift work: coping with the biological clock. Occup Med (Lond) 2010;60(1):10–20. doi:10.1093/occmed/kqp162. [Epub 2010/01/07]. PubMed PMID: 20051441. [3] Muller JE. Circadian variation in cardiovascular events. Am J Hypertens 1999;12(2 Pt 2):35S–42S. PubMed PMID: 10090293. [4] Smolensky MH, Portaluppi F. Chronopharmacology and chronotherapy of cardiovascular medications: relevance to prevention and treatment of coronary heart disease. Am Heart J 1999;137(4 Pt 2):S14–24. doi:a96908. [Epub 1999/ 03/31]. PubMed PMID: 10097242. [5] Fujino Y, Iso H, Tamakoshi A, et al. A prospective cohort study of shift work and risk of ischemic heart disease in Japanese male workers. Am J Epidemiol 2006;164(2):128–35. PubMed PMID: 16707650. [6] Mosendane T, Raal FJ. Shift work and its effects on the cardiovascular system. Cardiovasc J Afr 2008;19(4):210–15. [Epub 2008/09/09]. PubMed PMID: 18776968. [7] Scheer FA, Hilton MF, Mantzoros CS, et al. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci USA 2009;106(11):4453–8. doi:10.1073/pnas.0808180106. [Epub 2009/03/04]. PubMed PMID: 19255424, PMCID: 2657421. [8] Muller JE. Circadian variation and triggering of acute coronary events. Am Heart J 1999;137(4 Pt 2):S1–8. PubMed PMID: 10097240. [9] Li JJ. Circadian variation in myocardial ischemia: the possible mechanisms involving in this phenomenon. Med Hypotheses 2003;61(2):240–3. PubMed PMID: 12888312. [10] Boudreau P, Yeh WH, Dumont GA, et al. A circadian rhythm in heart rate variability contributes to the increased cardiac sympathovagal response to awakening in the morning. Chronobiol Int 2012;29(6):757–68. doi:10.3109/ 07420528.2012.674592. PubMed PMID: 22734576. [11] Gabel V, Maire M, Reichert CF, et al. Effects of artificial dawn and morning blue light on daytime cognitive performance, well-being, cortisol and melatonin levels. Chronobiol Int 2013;30(8):988–97. doi:10.3109/07420528.2013.793196. PubMed PMID: 23841684. [12] Lafrance C, Dumont M, Lesperance P, et al. Daytime vigilance after morning bright light exposure in volunteers subjected to sleep restriction. Physiol Behav 1998;63(5):803–10. PubMed PMID: 9618002.
[13] Munch M, Linhart F, Borisuit A, et al. Effects of prior light exposure on early evening performance, subjective sleepiness, and hormonal secretion. Behav Neurosci 2012;126(1):196–203. doi:10.1037/a0026702. PubMed PMID: 22201280. [14] Leichtfried V, Mair-Raggautz M, Schaeffer V, et al. Intense illumination in the morning hours improved mood and alertness but not mental performance. Appl Ergon 2015;46(Pt A):54–9. doi:10.1016/j.apergo.2014.07.001. PubMed PMID: 25106786. [15] Smolders KC, de Kort YA, Cluitmans PJ. A higher illuminance induces alertness even during office hours: findings on subjective measures, task performance and heart rate measures. Physiol Behav 2012;107(1):7–16. doi:10.1016/ j.physbeh.2012.04.028. PubMed PMID: 22564492. [16] Clow A, Thorn L, Evans P, et al. The awakening cortisol response: methodological issues and significance. Stress 2004;7(1):29–37. doi:10.1080/ 10253890410001667205. PubMed PMID: 15204030. [17] Thorn L, Hucklebridge F, Esgate A, et al. The effect of dawn simulation on the cortisol response to awakening in healthy participants. Psychoneuroendocrinology 2004;29(7):925–30. doi:10.1016/j.psyneuen.2003.08.005. PubMed PMID: 15177708. [18] Gabel V, Maire M, Reichert CF, et al. Dawn simulation light impacts on different cognitive domains under sleep restriction. Behav Brain Res 2014;281C:258–66. doi:10.1016/j.bbr.2014.12.043. PubMed PMID: 25549858. [19] Singh RB, Kartik C, Otsuka K, et al. Brain-heart connection and the risk of heart attack. Biomed Pharmacother 2002;56(Suppl. 2):257s–65s. PubMed PMID: 12653178. [20] Wehr TA. Effect of seasonal changes in daylength on human neuroendocrine function. Horm Res 1998;49(3–4):118–24. PubMed PMID: 9550111.
Jitka A.I. Virag * Department of Physiology, Brody School of Medicine, East Carolina University, 600 Moye Blvd, Greenville, NC 6N-98, USA * Tel.: +1 252 744 2777; fax: +1 252 744 5477. E-mail address: [email protected] Available online 26 January 2015
