Advertisement
Canadian Journal of Cardiology

Consequences of Circadian and Sleep Disturbances for the Cardiovascular System

Published:January 26, 2015DOI:https://doi.org/10.1016/j.cjca.2015.01.015

      Abstract

      Circadian rhythms play a crucial role in our cardiovascular system. Importantly, there has been a recent flurry of clinical and experimental studies revealing the profound adverse consequences of disturbing these rhythms on the cardiovascular system. For example, circadian disturbance worsens outcome after myocardial infarction with implications for patients in acute care settings. Moreover, disturbing rhythms exacerbates cardiac remodelling in heart disease models. Also, circadian dyssynchrony is a causal factor in the pathogenesis of heart disease. These discoveries have profound implications for the cardiovascular health of shift workers, individuals with circadian and sleep disorders, or anyone subjected to the 24/7 demands of society. Moreover, these studies give rise to 2 new frontiers for translational research: (1) circadian rhythms and the cardiac sarcomere, which sheds new light on our understanding of myofilament structure, signalling, and electrophysiology; and (2) knowledge translation, which includes biomarker discovery (chronobiomarkers), timing of therapies (chronotherapy), and other new promising approaches to improve the management and treatment of cardiovascular disease. Reconsidering circadian rhythms in the clinical setting benefits repair mechanisms, and offers new promise for patients.

      Résumé

      Les rythmes circadiens jouent un rôle crucial dans notre système cardiovasculaire. Notamment, une récente avalanche d’études cliniques et expérimentales révélant les conséquences indésirables profondes de la perturbation de ces rythmes sur le système cardiovasculaire ont été réalisées. Par exemple, la perturbation des rythmes circadiens détériore les résultats cliniques après l’infarctus du myocarde des patients en soins de phase aiguë. De plus, la perturbation des rythmes exacerbe le processus de remodelage cardiaque des modèles de cardiopathie. Aussi, la dyssynchronie circadienne est un facteur causal dans la pathogenèse de la cardiopathie. Ces découvertes ont de profondes conséquences sur la santé cardiovasculaire des travailleurs de quart, des individus ayant des troubles du rythme circadien et du sommeil, ou de tout individu soumis tous les jours 24 heures sur 24 aux exigences de la société. En outre, ces études mettent en exergue 2 nouvelles frontières de la recherche translationnelle : 1) les rythmes circadiens et le sarcomère cardiaque, lequel jette un nouvel éclairage sur notre compréhension de la structure des myofilaments, de la signalisation et de l’électrophysiologie; 2) l'application des connaissances, qui comprend la découverte des biomarqueurs (chronobiomarqueurs), le meilleur moment des thérapies (chronothérapie) et d’autres nouvelles approches prometteuses pour améliorer la prise en charge et le traitement de la maladie cardiovasculaire. La reconsidération des rythmes circadiens en milieu clinique favorise les mécanismes de réparation et s’avère prometteuse pour les patients.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Canadian Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Aschoff J.
        Circadian rhythms in man.
        Science. 1965; 148: 1427-1432
        • Hastings M.H.
        • Reddy A.B.
        • Maywood E.S.
        A clockwork web: circadian timing in brain and periphery, in health and disease.
        Nat Rev Neurosci. 2003; 4: 649-661
        • Reppert S.M.
        • Weaver D.R.
        Coordination of circadian timing in mammals.
        Nature. 2002; 418: 935-941
        • Roenneberg T.
        • Merrow M.
        Circadian clocks - the fall and rise of physiology.
        Nat Rev Mol Cell Biol. 2005; 6: 965-971
        • Durgan D.J.
        • Young M.E.
        The cardiomyocyte circadian clock: emerging roles in health and disease.
        Circ Res. 2010; 106: 647-658
        • Martino T.A.
        • Sole M.J.
        Molecular time: an often overlooked dimension to cardiovascular disease.
        Circ Res. 2009; 105: 1047-1061
        • Paschos G.K.
        • FitzGerald G.A.
        Circadian clocks and vascular function.
        Circ Res. 2010; 106: 833-841
        • Ko C.H.
        • Takahashi J.S.
        Molecular components of the mammalian circadian clock.
        Hum Mol Genet. 2006; 15: R271-R277
        • Dardente H.
        • Cermakian N.
        Molecular circadian rhythms in central and peripheral clocks in mammals.
        Chronobiol Int. 2007; 24: 195-213
        • Gamble K.L.
        • Berry R.
        • Frank S.J.
        • Young M.E.
        Circadian clock control of endocrine factors.
        Nat Rev Endocrinol. 2014; 10: 466-475
        • Evans J.A.
        • Davidson A.J.
        Health consequences of circadian disruption in humans and animal models.
        Prog Mol Biol Transl Sci. 2013; 119: 283-323
        • Sahar S.
        • Sassone-Corsi P.
        Metabolism and cancer: the circadian clock connection.
        Nat Rev Cancer. 2009; 9: 886-896
        • Bray M.S.
        • Shaw C.A.
        • Moore M.W.
        • et al.
        Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression.
        Am J Physiol Heart Circ Physiol. 2008; 294: H1036-H1047
        • Boivin D.B.
        Influence of sleep-wake and circadian rhythm disturbances in psychiatric disorders.
        J Psychiatry Neurosci. 2000; 25: 446-458
        • Smolensky M.H.
        • Portaluppi F.
        • Manfredini R.
        • et al.
        Diurnal and twenty-four hour patterning of human diseases: cardiac, vascular, and respiratory diseases, conditions, and syndromes.
        Sleep Med Rev. 2014; 14: 1-9
        • Clarke J.M.
        • Hamer J.
        • Shelton J.R.
        • Taylor S.
        • Venning G.R.
        The rhythm of the normal human heart.
        Lancet. 1976; 1: 508-512
        • Floras J.S.
        • Jones J.V.
        • Johnston J.A.
        • et al.
        Arousal and the circadian rhythm of blood pressure.
        Clin Sci Mol Med Suppl. 1978; 4: 395s-397s
        • Millar-Craig M.W.
        • Bishop C.N.
        • Raftery E.B.
        Circadian variation of blood-pressure.
        Lancet. 1978; 1: 795-797
        • Scheer F.A.
        • Hu K.
        • Evoniuk H.
        • et al.
        Impact of the human circadian system, exercise, and their interaction on cardiovascular function.
        Proc Natl Acad Sci U S A. 2010; 107: 20541-20546
        • Young M.E.
        • Razeghi P.
        • Cedars A.M.
        • Guthrie P.H.
        • Taegtmeyer H.
        Intrinsic diurnal variations in cardiac metabolism and contractile function.
        Circ Res. 2001; 89: 1199-1208
        • Saleh M.A.
        • Winget C.M.
        Effect of suprachiasmatic lesions on diurnal heart rate rhythm in the rat.
        Physiol Behav. 1977; 19: 561-564
        • Warren W.S.
        • Champney T.H.
        • Cassone V.M.
        The suprachiasmatic nucleus controls the circadian rhythm of heart rate via the sympathetic nervous system.
        Physiol Behav. 1994; 55: 1091-1099
        • Janssen B.J.
        • Tyssen C.M.
        • Duindam H.
        • Rietveld W.J.
        Suprachiasmatic lesions eliminate 24-h blood pressure variability in rats.
        Physiol Behav. 1994; 55: 307-311
        • Takezawa H.
        • Hayashi H.
        • Sano H.
        • Saito H.
        • Ebihara S.
        Circadian and estrous cycle-dependent variations in blood pressure and heart rate in female rats.
        Am J Physiol. 1994; 267: R1250-R1256
        • Sei H.
        • Oishi K.
        • Chikahisa S.
        • et al.
        Diurnal amplitudes of arterial pressure and heart rate are dampened in Clock mutant mice and adrenalectomized mice.
        Endocrinology. 2008; 149: 3576-3580
        • Curtis A.M.
        • Cheng Y.
        • Kapoor S.
        • et al.
        Circadian variation of blood pressure and the vascular response to asynchronous stress.
        Proc Natl Acad Sci U S A. 2007; 104: 3450-3455
        • Muller J.E.
        • Stone P.H.
        • Turi Z.G.
        • et al.
        Circadian variation in the frequency of onset of acute myocardial infarction.
        N Engl J Med. 1985; 313: 1315-1322
        • Cohen M.C.
        • Rohtla K.M.
        • Lavery C.E.
        • Muller J.E.
        • Mittleman M.A.
        Meta-analysis of the morning excess of acute myocardial infarction and sudden cardiac death.
        Am J Cardiol. 1997; 79: 1512-1516
        • Kanth R.
        • Ittaman S.
        • Rezkalla S.
        Circadian patterns of ST elevation myocardial infarction in the new millennium.
        Clin Med Res. 2013; 11: 66-72
        • Willich S.N.
        • Lowel H.
        • Lewis M.
        • et al.
        Association of wake time and the onset of myocardial infarction. Triggers and mechanisms of myocardial infarction (TRIMM) pilot study. TRIMM Study Group.
        Circulation. 1991; 84: VI62-VI67
        • Tofler G.H.
        • Muller J.E.
        • Stone P.H.
        • et al.
        Modifiers of timing and possible triggers of acute myocardial infarction in the Thrombolysis in Myocardial Infarction Phase II (TIMI II) Study Group.
        J Am Coll Cardiol. 1992; 20: 1049-1055
        • Tofler G.H.
        • Stone P.H.
        • Maclure M.
        • et al.
        Analysis of possible triggers of acute myocardial infarction (the MILIS study).
        Am J Cardiol. 1990; 66: 22-27
        • Goldberg R.J.
        • Brady P.
        • Muller J.E.
        • et al.
        Time of onset of symptoms of acute myocardial infarction.
        Am J Cardiol. 1990; 66: 140-144
        • Durgan D.J.
        • Pulinilkunnil T.
        • Villegas-Montoya C.
        • et al.
        Short communication: ischemia/reperfusion tolerance is time-of-day-dependent: mediation by the cardiomyocyte circadian clock.
        Circ Res. 2010; 106: 546-550
        • Reiter R.
        • Swingen C.
        • Moore L.
        • Henry T.D.
        • Traverse J.H.
        Circadian dependence of infarct size and left ventricular function after ST elevation myocardial infarction.
        Circ Res. 2012; 110: 105-110
        • Suarez-Barrientos A.
        • Lopez-Romero P.
        • Vivas D.
        • et al.
        Circadian variations of infarct size in acute myocardial infarction.
        Heart. 2011; 97: 970-976
        • Marler J.R.
        • Price T.R.
        • Clark G.L.
        • et al.
        Morning increase in onset of ischemic stroke.
        Stroke. 1989; 20: 473-476
        • Cannon C.P.
        • McCabe C.H.
        • Stone P.H.
        • et al.
        Circadian variation in the onset of unstable angina and non-Q-wave acute myocardial infarction (the TIMI III Registry and TIMI IIIB).
        Am J Cardiol. 1997; 79: 253-258
        • Tofler G.H.
        • Gebara O.C.
        • Mittleman M.A.
        • et al.
        Morning peak in ventricular tachyarrhythmias detected by time of implantable cardioverter/defibrillator therapy. The CPI Investigators.
        Circulation. 1995; 92: 1203-1208
        • Behrens S.
        • Galecka M.
        • Bruggemann T.
        • et al.
        Circadian variation of sustained ventricular tachyarrhythmias terminated by appropriate shocks in patients with an implantable cardioverter defibrillator.
        Am Heart J. 1995; 130: 79-84
        • Eksik A.
        • Akyol A.
        • Norgaz T.
        • et al.
        Circadian pattern of spontaneous ventricular tachyarrhythmias in patients with implantable cardioverter defibrillators.
        Med Sci Monit. 2007; 13: CR412-CR416
        • Venditti Jr., F.J.
        • John R.M.
        • Hull M.
        • et al.
        Circadian variation in defibrillation energy requirements.
        Circulation. 1996; 94: 1607-1612
        • Kong Jr., T.Q.
        • Goldberger J.J.
        • Parker M.
        • Wang T.
        • Kadish A.H.
        Circadian variation in human ventricular refractoriness.
        Circulation. 1995; 92: 1507-1516
        • Willich S.N.
        • Levy D.
        • Rocco M.B.
        • et al.
        Circadian variation in the incidence of sudden cardiac death in the Framingham Heart Study population.
        Am J Cardiol. 1987; 60: 801-806
        • Muller J.E.
        • Ludmer P.L.
        • Willich S.N.
        • et al.
        Circadian variation in the frequency of sudden cardiac death.
        Circulation. 1987; 75: 131-138
        • Willich S.N.
        • Goldberg R.J.
        • Maclure M.
        • Perriello L.
        • Muller J.E.
        Increased onset of sudden cardiac death in the first three hours after awakening.
        Am J Cardiol. 1992; 70: 65-68
        • Fava S.
        • Azzopardi J.
        • Muscat H.A.
        • Fenech F.F.
        Absence of circadian variation in the onset of acute myocardial infarction in diabetic subjects.
        Br Heart J. 1995; 74: 370-372
        • Kuniyoshi F.H.
        • Garcia-Touchard A.
        • Gami A.S.
        • et al.
        Day-night variation of acute myocardial infarction in obstructive sleep apnea.
        J Am Coll Cardiol. 2008; 52: 343-346
        • Zarich S.
        • Waxman S.
        • Freeman R.T.
        • et al.
        Effect of autonomic nervous system dysfunction on the circadian pattern of myocardial ischemia in diabetes mellitus.
        J Am Coll Cardiol. 1994; 24: 956-962
        • Ridker P.M.
        • Manson J.E.
        • Buring J.E.
        • Muller J.E.
        • Hennekens C.H.
        Circadian variation of acute myocardial infarction and the effect of low-dose aspirin in a randomized trial of physicians.
        Circulation. 1990; 82: 897-902
        • Ruggeri Z.M.
        Platelets in atherothrombosis.
        Nat Med. 2002; 8: 1227-1234
        • Scheer F.A.
        • Michelson A.D.
        • Frelinger 3rd, A.L.
        • et al.
        The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors.
        PLoS One. 2011; 6: e24549
        • Tofler G.H.
        • Brezinski D.
        • Schafer A.I.
        • et al.
        Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death.
        N Engl J Med. 1987; 316: 1514-1518
        • Andrews N.P.
        • Gralnick H.R.
        • Merryman P.
        • Vail M.
        • Quyyumi A.A.
        Mechanisms underlying the morning increase in platelet aggregation: a flow cytometry study.
        J Am Coll Cardiol. 1996; 28: 1789-1795
        • Decousus H.A.
        • Croze M.
        • Levi F.A.
        • et al.
        Circadian changes in anticoagulant effect of heparin infused at a constant rate.
        Br Med J (Clin Res Ed). 1985; 290: 341-344
        • Scheer F.A.
        • Shea S.A.
        Human circadian system causes a morning peak in prothrombotic plasminogen activator inhibitor-1 (PAI-1) independent of the sleep/wake cycle.
        Blood. 2014; 123: 590-593
        • Otto M.E.
        • Svatikova A.
        • Barretto R.B.
        • et al.
        Early morning attenuation of endothelial function in healthy humans.
        Circulation. 2004; 109: 2507-2510
        • Hu K.
        • Ivanov P.
        • Hilton M.F.
        • et al.
        Endogenous circadian rhythm in an index of cardiac vulnerability independent of changes in behavior.
        Proc Natl Acad Sci U S A. 2004; 101: 18223-18227
        • Maemura K.
        • de la Monte S.M.
        • Chin M.T.
        • et al.
        CLIF, a novel cycle-like factor, regulates the circadian oscillation of plasminogen activator inhibitor-1 gene expression.
        J Biol Chem. 2000; 275: 36847-36851
        • Schoenhard J.A.
        • Smith L.H.
        • Painter C.A.
        • et al.
        Regulation of the PAI-1 promoter by circadian clock components: differential activation by BMAL1 and BMAL2.
        J Mol Cell Cardiol. 2003; 35: 473-481
        • Oishi K.
        • Miyazaki K.
        • Uchida D.
        • et al.
        PERIOD2 is a circadian negative regulator of PAI-1 gene expression in mice.
        J Mol Cell Cardiol. 2009; 46: 545-552
        • Durgan D.J.
        • Moore M.W.
        • Ha N.P.
        • et al.
        Circadian rhythms in myocardial metabolism and contractile function: influence of workload and oleate.
        Am J Physiol Heart Circ Physiol. 2007; 293: H2385-H2393
        • Durgan D.J.
        • Pat B.M.
        • Laczy B.
        • et al.
        O-GlcNAcylation, novel post-translational modification linking myocardial metabolism and cardiomyocyte circadian clock.
        J Biol Chem. 2011; 286: 44606-44619
        • Chatham J.C.
        • Young M.E.
        Regulation of myocardial metabolism by the cardiomyocyte circadian clock.
        J Mol Cell Cardiol. 2013; 55: 139-146
        • Tsai J.Y.
        • Kienesberger P.C.
        • Pulinilkunnil T.
        • et al.
        Direct regulation of myocardial triglyceride metabolism by the cardiomyocyte circadian clock.
        J Biol Chem. 2010; 285: 2918-2929
        • Young M.E.
        • Brewer R.A.
        • Peliciari-Garcia R.A.
        • et al.
        Cardiomyocyte-specific BMAL1 plays critical roles in metabolism, signaling, and maintenance of contractile function of the heart.
        J Biol Rhythms. 2014; 29: 257-276
        • Storch K.F.
        • Lipan O.
        • Leykin I.
        • et al.
        Extensive and divergent circadian gene expression in liver and heart.
        Nature. 2002; 417: 78-83
        • Martino T.
        • Arab S.
        • Straume M.
        • et al.
        Day/night rhythms in gene expression of the normal murine heart.
        J Mol Med (Berl). 2004; 82: 256-264
        • Young M.E.
        • Razeghi P.
        • Taegtmeyer H.
        Clock genes in the heart: characterization and attenuation with hypertrophy.
        Circ Res. 2001; 88: 1142-1150
        • de Lichtenberg U.
        • Jensen L.J.
        • Fausboll A.
        • et al.
        Comparison of computational methods for the identification of cell cycle-regulated genes.
        Bioinformatics. 2005; 21: 1164-1171
        • Glynn E.F.
        • Chen J.
        • Mushegian A.R.
        Detecting periodic patterns in unevenly spaced gene expression time series using Lomb-Scargle periodograms.
        Bioinformatics. 2006; 22: 310-316
        • Hughes M.E.
        • Hogenesch J.B.
        • Kornacker K.
        JTK_CYCLE: an efficient nonparametric algorithm for detecting rhythmic components in genome-scale data sets.
        J Biol Rhythms. 2010; 25: 372-380
        • Pizarro A.
        • Hayer K.
        • Lahens N.F.
        • Hogenesch J.B.
        CircaDB: a database of mammalian circadian gene expression profiles.
        Nucleic Acids Res. 2013; 41: D1009-D1013
        • Leibetseder V.
        • Humpeler S.
        • Svoboda M.
        • et al.
        Clock genes display rhythmic expression in human hearts.
        Chronobiol Int. 2009; 26: 621-636
        • Davidson A.J.
        • London B.
        • Block G.D.
        • Menaker M.
        Cardiovascular tissues contain independent circadian clocks.
        Clin Exp Hypertens. 2005; 27: 307-311
        • Balsalobre A.
        • Damiola F.
        • Schibler U.
        A serum shock induces circadian gene expression in mammalian tissue culture cells.
        Cell. 1998; 93: 929-937
        • Durgan D.J.
        • Hotze M.A.
        • Tomlin T.M.
        • et al.
        The intrinsic circadian clock within the cardiomyocyte.
        Am J Physiol Heart Circ Physiol. 2005; 289: H1530-H1541
        • McNamara P.
        • Seo S.B.
        • Rudic R.D.
        • et al.
        Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock.
        Cell. 2001; 105: 877-889
        • Chalmers J.A.
        • Lin S.Y.
        • Martino T.A.
        • et al.
        Diurnal profiling of neuroendocrine genes in murine heart, and shift in proopiomelanocortin gene expression with pressure-overload cardiac hypertrophy.
        J Mol Endocrinol. 2008; 41: 117-124
        • Chalmers J.A.
        • Martino T.A.
        • Tata N.
        • et al.
        Vascular circadian rhythms in a mouse vascular smooth muscle cell line (Movas-1).
        Am J Physiol Regul Integr Comp Physiol. 2008; 295: R1529-R1538
        • Podobed P.
        • Pyle W.G.
        • Ackloo S.
        • et al.
        The day/night proteome in the murine heart.
        Am J Physiol Regul Integr Comp Physiol. 2014; 307: R121-R137
        • Reddy A.B.
        • Karp N.A.
        • Maywood E.S.
        • et al.
        Circadian orchestration of the hepatic proteome.
        Curr Biol. 2006; 16: 1107-1115
        • Luck S.
        • Thurley K.
        • Thaben P.F.
        • Westermark P.O.
        Rhythmic degradation explains and unifies circadian transcriptome and proteome data.
        Cell Rep. 2014; 9: 741-751
        • Ishida A.
        • Mutoh T.
        • Ueyama T.
        • et al.
        Light activates the adrenal gland: timing of gene expression and glucocorticoid release.
        Cell Metab. 2005; 2: 297-307
        • Lutzner N.
        • Kalbacher H.
        • Krones-Herzig A.
        • Rosl F.
        FOXO3 is a glucocorticoid receptor target and regulates LKB1 and its own expression based on cellular AMP levels via a positive autoregulatory loop.
        PLoS One. 2012; 7: e42166
        • Curtis A.M.
        • Seo S.B.
        • Westgate E.J.
        • et al.
        Histone acetyltransferase-dependent chromatin remodeling and the vascular clock.
        J Biol Chem. 2004; 279: 7091-7097
        • Innominato P.F.
        • Levi F.A.
        • Bjarnason G.A.
        Chronotherapy and the molecular clock: clinical implications in oncology.
        Adv Drug Deliv Rev. 2010; 62: 979-1001
        • Sole M.J.
        • Martino T.A.
        Diurnal physiology: core principles with application to the pathogenesis, diagnosis, prevention, and treatment of myocardial hypertrophy and failure.
        J Appl Physiol. 2009; 107: 1318-1327
        • Bass J.
        • Takahashi J.S.
        Circadian integration of metabolism and energetics.
        Science. 2010; 330: 1349-1354
        • Frangogiannis N.G.
        • Smith C.W.
        • Entman M.L.
        The inflammatory response in myocardial infarction.
        Cardiovasc Res. 2002; 53: 31-47
        • Mann D.L.
        The emerging role of innate immunity in the heart and vascular system: for whom the cell tolls.
        Circ Res. 2011; 108: 1133-1145
        • Nian M.
        • Lee P.
        • Khaper N.
        • Liu P.
        Inflammatory cytokines and postmyocardial infarction remodeling.
        Circ Res. 2004; 94: 1543-1553
        • Abo T.
        • Kawate T.
        • Itoh K.
        • Kumagai K.
        Studies on the bioperiodicity of the immune response. I. Circadian rhythms of human T, B, and K cell traffic in the peripheral blood.
        J Immunol. 1981; 126: 1360-1363
        • Born J.
        • Lange T.
        • Hansen K.
        • Molle M.
        • Fehm H.L.
        Effects of sleep and circadian rhythm on human circulating immune cells.
        J Immunol. 1997; 158: 4454-4464
        • Haus E.
        • Lakatua D.J.
        • Swoyer J.
        • Sackett-Lundeen L.
        Chronobiology in hematology and immunology.
        Am J Anat. 1983; 168: 467-517
        • Haus E.
        • Smolensky M.H.
        Biologic rhythms in the immune system.
        Chronobiol Int. 1999; 16: 581-622
        • Fortier E.E.
        • Rooney J.
        • Dardente H.
        • et al.
        Circadian variation of the response of T cells to antigen.
        J Immunol. 2011; 187: 6291-6300
        • Boivin D.B.
        • James F.O.
        • Wu A.
        • et al.
        Circadian clock genes oscillate in human peripheral blood mononuclear cells.
        Blood. 2003; 102: 4143-4145
        • Bollinger T.
        • Leutz A.
        • Leliavski A.
        • et al.
        Circadian clocks in mouse and human CD4+ T cells.
        PLoS One. 2011; 6: e29801
        • Oishi K.
        • Ohkura N.
        • Kadota K.
        • et al.
        Clock mutation affects circadian regulation of circulating blood cells.
        J Circadian Rhythms. 2006; 4: 13
        • Cermakian N.
        • Lange T.
        • Golombek D.
        • et al.
        Crosstalk between the circadian clock circuitry and the immune system.
        Chronobiol Int. 2013; 30: 870-888
        • Keller M.
        • Mazuch J.
        • Abraham U.
        • et al.
        A circadian clock in macrophages controls inflammatory immune responses.
        Proc Natl Acad Sci U S A. 2009; 106: 21407-21412
        • Alibhai F.J.
        • Tsimakouridze E.V.
        • Chinnappareddy N.
        • et al.
        Short-term disruption of diurnal rhythms after murine myocardial infarction adversely affects long-term myocardial structure and function.
        Circ Res. 2014; 114: 1713-1722
        • Patel M.
        • Chipman J.
        • Carlin B.W.
        • Shade D.
        Sleep in the intensive care unit setting.
        Crit Care Nurs Q. 2008; 31: 309-318
        • Buxton O.M.
        • Ellenbogen J.M.
        • Wang W.
        • et al.
        Sleep disruption due to hospital noises: a prospective evaluation.
        Ann Intern Med. 2012; 157: 170-179
        • Drouot X.
        • Cabello B.
        • d’Ortho M.P.
        • Brochard L.
        Sleep in the intensive care unit.
        Sleep Med Rev. 2008; 12: 391-403
        • Chan M.C.
        • Spieth P.M.
        • Quinn K.
        • et al.
        Circadian rhythms: from basic mechanisms to the intensive care unit.
        Crit Care Med. 2012; 40: 246-253
        • Stecker E.C.
        How can I recover if you won't let me sleep?.
        Sci Transl Med. 2014; 6: 231ec65
        • Penev P.D.
        • Kolker D.E.
        • Zee P.C.
        • Turek F.W.
        Chronic circadian desynchronization decreases the survival of animals with cardiomyopathic heart disease.
        Am J Physiol. 1998; 275: H2334-H2337
        • Martino T.A.
        • Tata N.
        • Belsham D.D.
        • et al.
        Disturbed diurnal rhythm alters gene expression and exacerbates cardiovascular disease with rescue by resynchronization.
        Hypertension. 2007; 49: 1104-1113
        • Lowrey P.L.
        • Shimomura K.
        • Antoch M.P.
        • et al.
        Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau.
        Science. 2000; 288: 483-492
        • Ralph M.R.
        • Menaker M.
        A mutation of the circadian system in golden hamsters.
        Science. 1988; 241: 1225-1227
        • Hurd M.W.
        • Ralph M.R.
        The significance of circadian organization for longevity in the golden hamster.
        J Biol Rhythms. 1998; 13: 430-436
        • Martino T.A.
        • Oudit G.Y.
        • Herzenberg A.M.
        • et al.
        Circadian rhythm disorganization produces profound cardiovascular and renal disease in hamsters.
        Am J Physiol Regul Integr Comp Physiol. 2008; 294: R1675-R1683
        • Lefta M.
        • Campbell K.S.
        • Feng H.Z.
        • Jin J.P.
        • Esser K.A.
        Development of dilated cardiomyopathy in Bmal1-deficient mice.
        Am J Physiol Heart Circ Physiol. 2012; 303: H475-H485
        • Durgan D.J.
        • Tsai J.Y.
        • Grenett M.H.
        • et al.
        Evidence suggesting that the cardiomyocyte circadian clock modulates responsiveness of the heart to hypertrophic stimuli in mice.
        Chronobiol Int. 2011; 28: 187-203
        • Woon P.Y.
        • Kaisaki P.J.
        • Braganca J.
        • et al.
        Aryl hydrocarbon receptor nuclear translocator-like (BMAL1) is associated with susceptibility to hypertension and type 2 diabetes.
        Proc Natl Acad Sci U S A. 2007; 104: 14412-14417
        • Englund A.
        • Kovanen L.
        • Saarikoski S.T.
        • et al.
        NPAS2 and PER2 are linked to risk factors of the metabolic syndrome.
        J Circadian Rhythms. 2009; 7: 5
        • Wang Q.
        • Maillard M.
        • Schibler U.
        • Burnier M.
        • Gachon F.
        Cardiac hypertrophy, low blood pressure, and low aldosterone levels in mice devoid of the three circadian PAR bZip transcription factors DBP, HLF, and TEF.
        Am J Physiol Regul Integr Comp Physiol. 2010; 299: R1013-R1019
        • Durgan D.J.
        • Trexler N.A.
        • Egbejimi O.
        • et al.
        The circadian clock within the cardiomyocyte is essential for responsiveness of the heart to fatty acids.
        J Biol Chem. 2006; 281: 24254-24269
        • Virag J.A.
        • Dries J.L.
        • Easton P.R.
        • et al.
        Attenuation of myocardial injury in mice with functional deletion of the circadian rhythm gene mPer2.
        Am J Physiol Heart Circ Physiol. 2010; 298: H1088-H1095
        • Eckle T.
        • Hartmann K.
        • Bonney S.
        • et al.
        Adora2b-elicited Per2 stabilization promotes a HIF-dependent metabolic switch crucial for myocardial adaptation to ischemia.
        Nat Med. 2012; 18: 774-782
      1. World Health Organization. World Health Report 2002: Reducing Risks, Promoting Healthy Life. Available at: http://www.who.int/whr/2002/en/. Accessed August 10, 2014.

        • Furlan R.
        • Barbic F.
        • Piazza S.
        • et al.
        Modifications of cardiac autonomic profile associated with a shift schedule of work.
        Circulation. 2000; 102: 1912-1916
        • Chau N.P.
        • Mallion J.M.
        • de Gaudemaris R.
        • et al.
        Twenty-four-hour ambulatory blood pressure in shift workers.
        Circulation. 1989; 80: 341-347
        • Scheer F.A.
        • Hilton M.F.
        • Mantzoros C.S.
        • Shea S.A.
        Adverse metabolic and cardiovascular consequences of circadian misalignment.
        Proc Natl Acad Sci U S A. 2009; 106: 4453-4458
        • Knutsson A.
        • Akerstedt T.
        • Jonsson B.G.
        • Orth-Gomer K.
        Increased risk of ischaemic heart disease in shift workers.
        Lancet. 1986; 2: 89-92
        • Kawachi I.
        • Colditz G.A.
        • Stampfer M.J.
        • et al.
        Prospective study of shift work and risk of coronary heart disease in women.
        Circulation. 1995; 92: 3178-3182
        • Vyas M.V.
        • Garg A.X.
        • Iansavichus A.V.
        • et al.
        Shift work and vascular events: systematic review and meta-analysis.
        BMJ. 2012; 345: e4800
        • Haupt C.M.
        • Alte D.
        • Dorr M.
        • et al.
        The relation of exposure to shift work with atherosclerosis and myocardial infarction in a general population.
        Atherosclerosis. 2008; 201: 205-211
        • Oishi M.
        • Suwazono Y.
        • Sakata K.
        • et al.
        A longitudinal study on the relationship between shift work and the progression of hypertension in male Japanese workers.
        J Hypertens. 2005; 23: 2173-2178
      2. Centers for Disease Control and Prevention. WorkSchedules: Shift Work and Long Work Hours. Available at: http://www.cdc.gov/niosh/topics/workschedules/. Accessed August 10, 2014.

        • Carrier J.
        • Monk T.H.
        Circadian rhythms of performance: new trends.
        Chronobiol Int. 2000; 17: 719-732
        • Toh K.L.
        • Jones C.R.
        • He Y.
        • et al.
        An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome.
        Science. 2001; 291: 1040-1043
      3. National Sleep Foundation. 2005 Sleep in America Poll. Available at: http://sleepfoundation.org/sites/default/files/2005_summary_of_findings.pdf. Accessed August 10, 2014.

        • Ayas N.T.
        • White D.P.
        • Manson J.E.
        • et al.
        A prospective study of sleep duration and coronary heart disease in women.
        Arch Intern Med. 2003; 163: 205-209
        • Wingard D.L.
        • Berkman L.F.
        Mortality risk associated with sleeping patterns among adults.
        Sleep. 1983; 6: 102-107
        • Kripke D.F.
        • Simons R.N.
        • Garfinkel L.
        • Hammond E.C.
        Short and long sleep and sleeping pills. Is increased mortality associated?.
        Arch Gen Psychiatry. 1979; 36: 103-116
      4. Healthy Sleep. Sleep and Disease Risk. Available at: http://healthysleep.med.harvard.edu/healthy/matters/consequences/sleep-and-disease-risk. Accessed on August 10, 2014.

        • Meerlo P.
        • Sgoifo A.
        • Suchecki D.
        Restricted and disrupted sleep: effects on autonomic function, neuroendocrine stress systems and stress responsivity.
        Sleep Med Rev. 2008; 12: 197-210
        • Buxton O.M.
        • Cain S.W.
        • O’Connor S.P.
        • et al.
        Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption.
        Sci Transl Med. 2012; 4: 129ra43
        • Anafi R.C.
        • Pellegrino R.
        • Shockley K.R.
        • et al.
        Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues.
        BMC Genomics. 2013; 14: 362
        • Duffy J.F.
        • Dijk D.J.
        • Hall E.F.
        • Czeisler C.A.
        Relationship of endogenous circadian melatonin and temperature rhythms to self-reported preference for morning or evening activity in young and older people.
        J Investig Med. 1999; 47: 141-150
        • Merikanto I.
        • Lahti T.
        • Puolijoki H.
        • et al.
        Associations of chronotype and sleep with cardiovascular diseases and type 2 diabetes.
        Chronobiol Int. 2013; 30: 470-477
        • Wittmann M.
        • Dinich J.
        • Merrow M.
        • Roenneberg T.
        Social jetlag: misalignment of biological and social time.
        Chronobiol Int. 2006; 23: 497-509
        • Rutters F.
        • Lemmens S.G.
        • Adam T.C.
        • et al.
        Is social jetlag associated with an adverse endocrine, behavioral, and cardiovascular risk profile?.
        J Biol Rhythms. 2014; 29: 377-383
        • Czeisler C.A.
        Perspective: casting light on sleep deficiency.
        Nature. 2013; 497: S13
        • Chang A.
        • Aeschbach D.
        • Duffy J.F.
        • Czeisler C.A.
        Evening use of light-emitting eReaders negatively affects sleep, circadian timing, and next-morning alertness.
        Proc Natl Acad Sci U S A. 2015; 112: 1232-1237
        • Pyle W.G.
        • Solaro R.J.
        At the crossroads of myocardial signaling: the role of Z-discs in intracellular signaling and cardiac function.
        Circ Res. 2004; 94: 296-305
        • Frank D.
        • Frey N.
        Cardiac Z-disc signaling network.
        J Biol Chem. 2011; 286: 9897-9904
        • Solaro R.J.
        • Kobayashi T.
        Protein phosphorylation and signal transduction in cardiac thin filaments.
        J Biol Chem. 2011; 286: 9935-9940
        • Palmer B.M.
        Thick filament proteins and performance in human heart failure.
        Heart Fail Rev. 2005; 10: 187-197
        • Podobed P.S.
        • Alibhai F.J.
        • Chow C.W.
        • Martino T.A.
        Circadian regulation of myocardial sarcomeric Titin-cap (Tcap, Telethonin): identification of cardiac clock-controlled genes using open access bioinformatics data.
        PLoS One. 2014; 9: e104907
        • Andrews J.L.
        • Zhang X.
        • McCarthy J.J.
        • et al.
        CLOCK and BMAL1 regulate MyoD and are necessary for maintenance of skeletal muscle phenotype and function.
        Proc Natl Acad Sci U S A. 2010; 107: 19090-19095
        • Collins H.E.
        • Rodrigo G.C.
        Inotropic response of cardiac ventricular myocytes to beta-adrenergic stimulation with isoproterenol exhibits diurnal variation: involvement of nitric oxide.
        Circ Res. 2010; 106: 1244-1252
        • Collins H.E.
        • Turrell H.E.
        • Samani N.J.
        • Rodrigo G.C.
        Diurnal variation in excitation-contraction coupling is lost in the adult spontaneously hypertensive rat heart.
        J Hypertens. 2013; 31: 1214-1223
        • Ko M.L.
        • Shi L.
        • Grushin K.
        • Nigussie F.
        • Ko G.Y.
        Circadian profiles in the embryonic chick heart: L-type voltage-gated calcium channels and signaling pathways.
        Chronobiol Int. 2010; 27: 1673-1696
        • Yamashita T.
        • Sekiguchi A.
        • Iwasaki Y.K.
        • et al.
        Circadian variation of cardiac K+ channel gene expression.
        Circulation. 2003; 107: 1917-1922
        • Ko M.L.
        • Shi L.
        • Tsai J.Y.
        • et al.
        Cardiac-specific mutation of Clock alters the quantitative measurements of physical activities without changing behavioral circadian rhythms.
        J Biol Rhythms. 2011; 26: 412-422
        • Jeyaraj D.
        • Haldar S.M.
        • Wan X.
        • et al.
        Circadian rhythms govern cardiac repolarization and arrhythmogenesis.
        Nature. 2012; 483: 96-99
        • Schroder E.A.
        • Lefta M.
        • Zhang X.
        • et al.
        The cardiomyocyte molecular clock, regulation of Scn5a, and arrhythmia susceptibility.
        Am J Physiol Cell Physiol. 2013; 304: C954-C965
        • Ueda H.R.
        • Chen W.
        • Minami Y.
        • et al.
        Molecular-timetable methods for detection of body time and rhythm disorders from single-time-point genome-wide expression profiles.
        Proc Natl Acad Sci U S A. 2004; 101: 11227-11232
        • Minami Y.
        • Kasukawa T.
        • Kakazu Y.
        • et al.
        Measurement of internal body time by blood metabolomics.
        Proc Natl Acad Sci U S A. 2009; 106: 9890-9895
        • Kasukawa T.
        • Sugimoto M.
        • Hida A.
        • et al.
        Human blood metabolite timetable indicates internal body time.
        Proc Natl Acad Sci U S A. 2012; 109: 15036-15041
        • Tsimakouridze E.V.
        • Straume M.
        • Podobed P.S.
        • et al.
        Chronomics of pressure overload-induced cardiac hypertrophy in mice reveals altered day/night gene expression and biomarkers of heart disease.
        Chronobiol Int. 2012; 29: 810-821
        • Martino T.A.
        • Tata N.
        • Bjarnason G.A.
        • Straume M.
        • Sole M.J.
        Diurnal protein expression in blood revealed by high throughput mass spectrometry proteomics and implications for translational medicine and body time of day.
        Am J Physiol Regul Integr Comp Physiol. 2007; 293: R1430-R1437
        • Martino T.A.
        • Tata N.
        • Simpson J.A.
        • et al.
        The primary benefits of angiotensin-converting enzyme inhibition on cardiac remodeling occur during sleep time in murine pressure overload hypertrophy.
        J Am Coll Cardiol. 2011; 57: 2020-2028
        • Zhang R.
        • Lahens N.F.
        • Ballance H.I.
        • Hughes M.E.
        • Hogenesch J.B.
        A circadian gene expression atlas in mammals: implications for biology and medicine.
        Proc Natl Acad Sci U S A. 2014; 111: 16219-16224
        • Verdecchia P.
        • Schillaci G.
        • Gatteschi C.
        • et al.
        Blunted nocturnal fall in blood pressure in hypertensive women with future cardiovascular morbid events.
        Circulation. 1993; 88: 986-992
        • Ohkubo T.
        • Hozawa A.
        • Yamaguchi J.
        • et al.
        Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study.
        J Hypertens. 2002; 20: 2183-2189
        • Clement D.L.
        • De Buyzere M.L.
        • De Bacquer D.A.
        • et al.
        Prognostic value of ambulatory blood-pressure recordings in patients with treated hypertension.
        N Engl J Med. 2003; 348: 2407-2415
        • Perloff D.
        • Sokolow M.
        • Cowan R.
        The prognostic value of ambulatory blood pressures.
        JAMA. 1983; 249: 2792-2798
        • Kikuya M.
        • Ohkubo T.
        • Asayama K.
        • et al.
        Ambulatory blood pressure and 10-year risk of cardiovascular and noncardiovascular mortality: the Ohasama study.
        Hypertension. 2005; 45: 240-245
        • Hermida R.C.
        • Smolensky M.H.
        • Ayala D.E.
        • et al.
        2013 Ambulatory blood pressure monitoring recommendations for the diagnosis of adult hypertension, assessment of cardiovascular and other hypertension-associated risk, and attainment of therapeutic goals (summary). Joint recommendations from the International Society for Chronobiology (ISC), American Association of Medical Chronobiology and Chronotherapeutics (AAMCC), Spanish Society of Applied Chronobiology, Chronotherapy, and Vascular Risk (SECAC), Spanish Society of Atherosclerosis (SEA), and Romanian Society of Internal Medicine (RSIM).
        Clin Investig Arterioscler. 2013; 25 ([in Spanish]): 74-82
        • Hermida R.C.
        • Ayala D.E.
        • Smolensky M.H.
        • et al.
        Chronotherapeutics of conventional blood pressure-lowering medications: simple, low-cost means of improving management and treatment outcomes of hypertensive-related disorders.
        Curr Hypertens Rep. 2014; 16: 412
        • Hermida R.C.
        • Ayala D.E.
        • Smolensky M.H.
        • et al.
        Chronotherapy improves blood pressure control and reduces vascular risk in CKD.
        Nat Rev Nephrol. 2013; 9: 358-368
        • Hermida R.C.
        • Ayala D.E.
        • Fernandez J.R.
        • et al.
        Administration-time differences in effects of hypertension medications on ambulatory blood pressure regulation.
        Chronobiol Int. 2013; 30: 280-314
        • Smolensky M.H.
        • Hermida R.C.
        • Ayala D.E.
        • Tiseo R.
        • Portaluppi F.
        Administration-time-dependent effects of blood pressure-lowering medications: basis for the chronotherapy of hypertension.
        Blood Press Monit. 2010; 15: 173-180
        • Hermida R.C.
        • Ayala D.E.
        Chronotherapy with the angiotensin-converting enzyme inhibitor ramipril in essential hypertension: improved blood pressure control with bedtime dosing.
        Hypertension. 2009; 54: 40-46
        • Hermida R.C.
        • Ayala D.E.
        • Fernandez J.R.
        • Calvo C.
        Comparison of the efficacy of morning versus evening administration of telmisartan in essential hypertension.
        Hypertension. 2007; 50: 715-722
        • Hermida R.C.
        • Ayala D.E.
        • Fontao M.J.
        • Mojon A.
        • Fernandez J.R.
        Chronotherapy with valsartan/amlodipine fixed combination: improved blood pressure control of essential hypertension with bedtime dosing.
        Chronobiol Int. 2010; 27: 1287-1303
        • Hermida R.C.
        • Ayala D.E.
        • Mojon A.
        • Fernandez J.R.
        Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study.
        Chronobiol Int. 2010; 27: 1629-1651
        • Ayas N.T.
        • Hirsch A.A.
        • Laher I.
        • et al.
        New frontiers in obstructive sleep apnoea.
        Clin Sci (Lond). 2014; 127: 209-216
        • Kasai T.
        • Bradley T.D.
        Obstructive sleep apnea and heart failure: pathophysiologic and therapeutic implications.
        J Am Coll Cardiol. 2011; 57: 119-127
        • Floras J.S.
        Sleep apnea and cardiovascular risk.
        J Cardiol. 2014; 63: 3-8
        • Somers V.K.
        • White D.P.
        • Amin R.
        • et al.
        Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing.
        J Am Coll Cardiol. 2008; 52: 686-717
        • Bradley T.D.
        • Floras J.S.
        Sleep apnea and heart failure: part I: obstructive sleep apnea.
        Circulation. 2003; 107: 1671-1678
        • Bradley T.D.
        • Floras J.S.
        Obstructive sleep apnoea and its cardiovascular consequences.
        Lancet. 2009; 373: 82-93
        • Usui K.
        • Bradley T.D.
        • Spaak J.
        • et al.
        Inhibition of awake sympathetic nerve activity of heart failure patients with obstructive sleep apnea by nocturnal continuous positive airway pressure.
        J Am Coll Cardiol. 2005; 45: 2008-2011
        • Somers V.K.
        • Dyken M.E.
        • Clary M.P.
        • Abboud F.M.
        Sympathetic neural mechanisms in obstructive sleep apnea.
        J Clin Invest. 1995; 96: 1897-1904
        • Kaneko Y.
        • Floras J.S.
        • Usui K.
        • et al.
        Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea.
        N Engl J Med. 2003; 348: 1233-1241
        • Arias M.A.
        • Garcia-Rio F.
        • Alonso-Fernandez A.
        • et al.
        Obstructive sleep apnea syndrome affects left ventricular diastolic function: effects of nasal continuous positive airway pressure in men.
        Circulation. 2005; 112: 375-383
        • Tkacova R.
        • Rankin F.
        • Fitzgerald F.S.
        • Floras J.S.
        • Bradley T.D.
        Effects of continuous positive airway pressure on obstructive sleep apnea and left ventricular afterload in patients with heart failure.
        Circulation. 1998; 98: 2269-2275
        • Pepperell J.C.
        • Ramdassingh-Dow S.
        • Crosthwaite N.
        • et al.
        Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial.
        Lancet. 2002; 359: 204-210
        • Burioka N.
        • Koyanagi S.
        • Endo M.
        • et al.
        Clock gene dysfunction in patients with obstructive sleep apnoea syndrome.
        Eur Respir J. 2008; 32: 105-112
        • Chan C.T.
        • Floras J.S.
        • Miller J.A.
        • Richardson R.M.
        • Pierratos A.
        Regression of left ventricular hypertrophy after conversion to nocturnal hemodialysis.
        Kidney Int. 2002; 61: 2235-2239
        • Culleton B.F.
        • Walsh M.
        • Klarenbach S.W.
        • et al.
        Effect of frequent nocturnal hemodialysis vs conventional hemodialysis on left ventricular mass and quality of life: a randomized controlled trial.
        JAMA. 2007; 298: 1291-1299
        • Chan C.T.
        • Arab S.
        • Carasso S.
        • et al.
        Impact of frequent nocturnal hemodialysis on myocardial mechanics and cardiomyocyte gene expression.
        Circ Cardiovasc Imaging. 2012; 5: 474-480
        • Bonten T.N.
        • Saris A.
        • van Oostrom M.J.
        • et al.
        Effect of aspirin intake at bedtime versus on awakening on circadian rhythm of platelet reactivity. A randomised cross-over trial.
        Thromb Haemost. 2014; 112: 1209-1218
      5. Heart and Stroke Foundation of Canada. Statistics. Stroke. Available at: http://www.heartandstroke.com/site/c.ikIQLcMWJtE/b.3483991/k.34A8/Statistics.htm#stroke. Accessed August 20, 2014.