Chapter 028. Sleep Disorders (Part 15) Medical Implications of Circadian Rhythmicity Prominent circadian variations have been reported in the incidence of acute myocardial infarction, sudden cardiac death, and stroke, the leading causes of death in the United States. Platelet aggregability is increased after arising in the early morning hours, coincident with the peak incidence of these cardiovascular events. A better understanding of the possible role of circadian rhythmicity in the acute destabilization of a chronic condition such as atherosclerotic disease could improve the understanding of the pathophysiology. Diagnostic and therapeutic procedures may also be affected by the time of day at which data are collected. Examples include blood pressure, body temperature, the dexamethasone suppression test, and plasma cortisol levels. The timing of chemotherapy administration has been reported to have an effect on the outcome of treatment. Few physicians realize the extent to which routine measures are affected by the time (or sleep/wake state) when the measurement is made. In addition, both the toxicity and effectiveness of drugs can vary during the day. For example, more than a fivefold difference has been observed in mortality rates following administration of toxic agents to experimental animals at different times of day. Anesthetic agents are particularly sensitive to time-of-day effects. Finally, the physician must be increasingly aware of the public health risks associated with the ever-increasing demands made by the duty-rest-recreation schedules in our round-the-clock society. Further Readings Flemons WW: Clinical practice. Obstructive sleep apnea. N Engl J Med 347:498, 2002 [PMID: 12181405] Pack AI et al: Risk factors for excessive sleepiness in older adults. Ann Neurol 59:893, 2006 [PMID: 16718691] Scammell TE: The neurobiology, diagnosis, and treatment of narcolepsy. Ann Neurol 53:154, 2003 [PMID: 12557281] Silber MH: Clinical practice. Chronic insomnia. N Engl J Med 353:803, 2005 [PMID: 16120860] Bibliography Allen RP et al: Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 165:1286, 2005 [PMID: 15956009] Arendt J: Importance and relevance of melatonin to human biological rhythms. J Neuroendocrinol 15:427, 2003 [PMID: 12622845] Ayas NT et al: Extended work duration and the risk of self- reported percutaneous injuries in interns. JAMA 296:1055, 2006 [PMID: 16954484] Barger LK et al: Extended work shifts and the risk of motor vehicle crashes among interns. N Engl J Med 352:125, 2005 [PMID: 15647575] Barger LK et al: Impact of extended- duration shifts on medical errors, adverse events, and attentional failures. PLoS Med 3:2440, 2006 Berson DM et al: Phototransduction by retinal ganglion cells that s et the circadian clock. Science 295:1070, 2002 [PMID: 11834835] Cajochen C et al: Separation of circadian and wake duration- dependent modulation of EEG activation during wakefulness. Neuroscience 114:1047, 2002 [PMID: 12379258] Kamel NS, Gammack JK: In somnia in the elderly: Cause, approach, and treatment. Am J Med 119:463, 2006 [PMID: 16750956] Czeisler CA et al: Stability, precision, and near-24- hour period of the human circadian pacemaker. Science 284:2177, 1999 [PMID: 10381883] Czeisler CA et al: Modafinil for excessive sleepiness associated with shift work sleep disorder. N Engl J Med 353:476, 2005 [PMID: 16079371] Dijk D-J, Lockley SW: Integration of human sleep- wake regulation and circadian rhythmicity. J Appl Physiol 92:852, 2002 [PMID: 11796701] Fantini ML et al: Idiopathic REM sleep behavior disorder: Toward a better nosologic definition. Neurology 64:780, 2005 [PMID: 15753409] Horowitz TS et al: Efficacy of bright light and sleep/darkness scheduling in alleviating circadian maladaptati on to night work. Am J Physiol Endocrinol Metab 281:E384, 2001 Kryger MH et al (eds): Principles and Practice of Sleep Medicine , 4th ed. Philadelphia, Saunders, 2005 Kushida CA et al: Practice parameters for the indications for polysomnography and rela ted procedures: An update for 2005. Sleep 28:499, 2005 [PMID: 16171294] Landrigan CP et al: Effect of reducing interns' work hours on serious medical errors in intensive care units. N Engl J Med 351:1838, 2004 [PMID: 15509817] Lockley SW et al: Effect of reducing interns' weekly work hours on sleep and attentional failures. N Engl J Med 351:1829, 2004 [PMID: 15509816] Lockley SW et al: High sensitivity of the human circadian melatonin rhythm for resetting by short wavelength light. J Clin Endocrinol M etab 9:4502, 2003 Mahowald MW, Schenck CH: Insights from studying human sleep disorders. Nature 437:1279, 2005 [PMID: 16251953] Malhotra A, White DP: Obstructive sleep apnoea. Lancet 360:237, 2002 [PMID: 12133673] Mignot E et al: Sleeping with the hy pothalamus: Emerging therapeutic targets for sleep disorders. Nat Neurosci 5:1071, 2002 [PMID: 12403989] National Institutes of Health: State of the Science Conference statement on Manifestations and Management of Chronic Insomnia in Adults, June 13– 15, 2005. Sleep 28:1049, 2005 Reppert SM, Weaver D: Coordination of circadian timing in mammals. Nature 418:935, 2002 [PMID: 12198538] Saper CB et al: Hypothalamic regulation of sleep and circadian rhythms. Nature 437:1257, 2005 [PMID: 16251950] Storch K F et al: Extensive and divergent circadian gene expression in liver and heart. Nature 417:78, 2002 [PMID: 11967526] Tafti M et al: Genes for normal sleep and sleep disorders. Ann Med 37:580, 2005 [PMID: 16338760] Trenkwalder C et al: The restless legs syndrome. Lancet Neurol 4:465, 2005 [PMID: 16033689] Van Dongen HP et al: The cumulative cost of additional wakefulness: Dose- response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep 26:117, 2003 Young MW et al: Time zones: A comparative genetics of circadian clocks. Nat Rev Genet 2:702, 2001 [PMID: 11533719] Wyatt JK et al: Sleep facilitating effect of exogenous melatonin in healthy young men and women is circadian-phase depe ndent. Sleep 29:609, 2006 [PMID: 16774150] . Chapter 028. Sleep Disorders (Part 15) Medical Implications of Circadian Rhythmicity Prominent circadian variations. studying human sleep disorders. Nature 437:1279, 2005 [PMID: 16251953] Malhotra A, White DP: Obstructive sleep apnoea. Lancet 360:237, 2002 [PMID: 12133673] Mignot E et al: Sleeping with the. Dose- response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep 26:117, 2003 Young MW et al: Time zones: A comparative