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Current Vascular Pharmacology

Editor-in-Chief

ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

General Review Article

Cardiovascular Complications of Sleep Disorders: A Better Night’s Sleep for a Healthier Heart / From Bench to Bedside

Author(s): Theodora A. Manolis, Antonis A. Manolis , Evdoxia J. Apostolopoulos , Helen Melita and Antonis S. Manolis*

Volume 19, Issue 2, 2021

Published on: 25 March, 2020

Page: [210 - 232] Pages: 23

DOI: 10.2174/1570161118666200325102411

Price: $65

Abstract

Sleep is essential to and an integral part of life and when lacking or disrupted, a multitude of mental and physical pathologies ensue, including cardiovascular (CV) disease, which increases health care costs. Several prospective studies and meta-analyses show that insomnia, short (<7h) or long (>9h) sleep and other sleep disorders are associated with an increased risk of hypertension, metabolic syndrome, myocardial infarction, heart failure, arrhythmias, CV disease risk and/or mortality. The mechanisms by which insomnia and other sleep disorders lead to increased CV risk may encompass inflammatory, immunological, neuro-autonomic, endocrinological, genetic and microbiome perturbations. Guidelines are emerging that recommend a target of >7 h of sleep for all adults >18 years for optimal CV health. Treatment of sleep disorders includes cognitive-behavioral therapy considered the mainstay of non-pharmacologic management of chronic insomnia, and drug treatment with benzodiazepine receptor agonists binding to gamma aminobutyric acid type A (benzodiazepine and non-benzodiazepine agents) and some antidepressants. However, observational studies and meta-analyses indicate an increased mortality risk of anxiolytics and hypnotics, although bias may be involved due to confounding and high heterogeneity in these studies. Nevertheless, it seems that the risk incurred by the non-benzodiazepine hypnotic agents (Z drugs) may be relatively less than the risk of anxiolytics, with evidence indicating that at least one of these agents, zolpidem, may even confer a lower risk of mortality in adjusted models. All these issues are herein reviewed.

Keywords: Sleep disorders, insomnia, cardiovascular disease, cardiovascular mortality, myocardial infarction, short sleep, long sleep, daytime napping, siesta.

Graphical Abstract

[1]
St-Onge MP, Grandner MA, Brown D, et al. Sleep duration and quality: impact on lifestyle behaviors and cardiometabolic health: a scientific statement from the American heart association. Circulation 2016; 134(18): e367-86.
[http://dx.doi.org/10.1161/CIR.0000000000000444] [PMID: 27647451]
[2]
Wittchen HU, Jacobi F, Rehm J, et al. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 2011; 21(9): 655-79.
[http://dx.doi.org/10.1016/j.euroneuro.2011.07.018] [PMID: 21896369]
[3]
Lloyd-Jones DM, Hong Y, Labarthe D, et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic Impact Goal through 2020 and beyond. Circulation 2010; 121(4): 586-613.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.192703] [PMID: 20089546]
[4]
Folsom AR, Shah AM, Lutsey PL, et al. American heart association’s life’s simple 7: avoiding heart failure and preserving cardiac structure and function. Am J Med 2015; 128(9): 970-6.
[http://dx.doi.org/10.1016/j.amjmed.2015.03.027] [PMID: 25908393]
[5]
Ogunmoroti O, Oni E, Michos ED, et al. Life’s simple 7 and incident heart failure: the multi-ethnic study of atherosclerosis. J Am Heart Assoc 2017; 6(6)e005180
[http://dx.doi.org/10.1161/JAHA.116.005180] [PMID: 28655734]
[6]
Kulshreshtha A, Vaccarino V, Judd SE, et al. Life’s simple 7 and risk of incident stroke: the reasons for geographic and racial differences in stroke study. Stroke 2013; 44(7): 1909-14.
[http://dx.doi.org/10.1161/STROKEAHA.111.000352] [PMID: 23743971]
[7]
Lloyd-Jones DM. Cardiovascular health and protection against CVD: more than the sum of the parts? Circulation 2014; 130(19): 1671-3.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.114.012869] [PMID: 25273999]
[8]
Younus A, Aneni EC, Spatz ES, et al. A systematic review of the prevalence and outcomes of ideal cardiovascular health in US and non-us populations. Mayo Clin Proc 2016; 91(5): 649-70.
[http://dx.doi.org/10.1016/j.mayocp.2016.01.019] [PMID: 27040086]
[9]
Ogunmoroti O, Allen NB, Cushman M, et al. Association between life’s simple 7 and noncardiovascular disease: the multi-ethnic study of atherosclerosis. J Am Heart Assoc 2016; 5(10)e003954
[http://dx.doi.org/10.1161/JAHA.116.003954] [PMID: 27792654]
[10]
Makarem N, St-Onge MP, Liao M, Lloyd-Jones DM, Aggarwal B. Association of sleep characteristics with cardiovascular health among women and differences by race/ethnicity and menopausal status: findings from the American heart association go red for women strategically focused research network. Sleep Health 2019; 5(5): 501-8.
[http://dx.doi.org/10.1016/j.sleh.2019.05.005] [PMID: 31302068]
[11]
Sateia MJ. International classification of sleep disorders-third edition: highlights and modifications. Chest 2014; 146(5): 1387-94.
[http://dx.doi.org/10.1378/chest.14-0970] [PMID: 25367475]
[12]
Léger D, Poursain B, Neubauer D, Uchiyama M. An international survey of sleeping problems in the general population. Curr Med Res Opin 2008; 24(1): 307-17.
[http://dx.doi.org/10.1185/030079907X253771] [PMID: 18070379]
[13]
Ohayon MM. Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med Rev 2002; 6(2): 97-111.
[http://dx.doi.org/10.1053/smrv.2002.0186] [PMID: 12531146]
[14]
Ohayon MM, Smirne S. Prevalence and consequences of insomnia disorders in the general population of Italy. Sleep Med 2002; 3(2): 115-20.
[http://dx.doi.org/10.1016/S1389-9457(01)00158-7] [PMID: 14592229]
[15]
Buysse DJ. Insomnia. JAMA 2013; 309(7): 706-16.
[http://dx.doi.org/10.1001/jama.2013.193] [PMID: 23423416]
[16]
Benca RM. Diagnosis and treatment of chronic insomnia: a review. Psychiatr Serv 2005; 56(3): 332-43.
[http://dx.doi.org/10.1176/appi.ps.56.3.332] [PMID: 15746509]
[17]
Simon GE, VonKorff M. Prevalence, burden, and treatment of insomnia in primary care. Am J Psychiatry 1997; 154(10): 1417-23.
[http://dx.doi.org/10.1176/ajp.154.10.1417] [PMID: 9326825]
[18]
Bassetti CLA, Adamantidis A, Burdakov D, et al. Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment. Nat Rev Neurol 2019; 15(9): 519-39.
[http://dx.doi.org/10.1038/s41582-019-0226-9] [PMID: 31324898]
[19]
Roth T, Dauvilliers Y, Mignot E, et al. Disrupted nighttime sleep in narcolepsy. J Clin Sleep Med 2013; 9(9): 955-65.
[http://dx.doi.org/10.5664/jcsm.3004] [PMID: 23997709]
[20]
Dasopoulou C, Metaxa S, Tsagou V, Michaelides J, Koulouris S, Manolis AS. Sleep apnea syndrome: More than benign snoring, im-plications for the cardiovascular system. Hosp Chron 2011; 6(4): 155-73.
[21]
Pafili K, Steiropoulos P, Papanas N. The relationship between obstructive sleep apnoea and coronary heart disease. Curr Opin Cardiol 2015; 30(4): 439-46.
[http://dx.doi.org/10.1097/HCO.0000000000000172] [PMID: 26049394]
[22]
Steiropoulos P, Papanas N. Obstructive sleep apnea and atrial fibrillation: do they synergistically increase cardiovascular risk? Angiology 2015; 66(6): 501-2.
[http://dx.doi.org/10.1177/0003319714568446] [PMID: 25593210]
[23]
Voulgaris A, Archontogeorgis K, Papanas N, et al. Increased risk for cardiovascular disease in patients with obstructive sleep apnoea syndrome-chronic obstructive pulmonary disease (overlap syndrome). Clin Respir J 2019; 13(11): 708-15.
[http://dx.doi.org/10.1111/crj.13078] [PMID: 31433558]
[24]
Somers VK, White DP, 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(8): 686-717.
[http://dx.doi.org/10.1016/j.jacc.2008.05.002] [PMID: 18702977]
[25]
Spielman AJ, Caruso LS, Glovinsky PB. A behavioral perspective on insomnia treatment. Psychiatr Clin North Am 1987; 10(4): 541-53.
[http://dx.doi.org/10.1016/S0193-953X(18)30532-X] [PMID: 3332317]
[26]
Palagini L, Biber K, Riemann D. The genetics of insomnia--evidence for epigenetic mechanisms? Sleep Med Rev 2014; 18(3): 225-35.
[http://dx.doi.org/10.1016/j.smrv.2013.05.002] [PMID: 23932332]
[27]
Chakravorty S, Chaudhary NS, Brower KJ. Alcohol dependence and its relationship with insomnia and other sleep disorders. Alcohol Clin Exp Res 2016; 40(11): 2271-82.
[http://dx.doi.org/10.1111/acer.13217] [PMID: 27706838]
[28]
Sutton EL. Insomnia. Med Clin North Am 2014; 98(3): 565-81.
[http://dx.doi.org/10.1016/j.mcna.2014.01.008] [PMID: 24758961]
[29]
Zhu L, Zee PC. Circadian rhythm sleep disorders. Neurol Clin 2012; 30(4): 1167-91.
[http://dx.doi.org/10.1016/j.ncl.2012.08.011] [PMID: 23099133]
[30]
Khan S, Malik BH, Gupta D, Rutkofsky I. The role of circadian misalignment due to insomnia, lack of sleep, and shift work in increasing the risk of cardiac diseases: a systematic review. Cureus 2020; 12(1)e6616
[http://dx.doi.org/10.7759/cureus.6616] [PMID: 32064196]
[31]
Zheng B, Yu C, Lv J, et al. Insomnia symptoms and risk of cardiovascular diseases among 0.5 million adults: A 10-year cohort. Neurology 2019; 93(23): e2110-20.
[http://dx.doi.org/10.1212/WNL.0000000000008581] [PMID: 31694922]
[32]
Ge L, Guyatt G, Tian J, et al. Insomnia and risk of mortality from all-cause, cardiovascular disease, and cancer: Systematic review and meta-analysis of prospective cohort studies. Sleep Med Rev 2019; 48101215
[http://dx.doi.org/10.1016/j.smrv.2019.101215] [PMID: 31630016]
[33]
Laugsand LE, Vatten LJ, Platou C, Janszky I. Insomnia and the risk of acute myocardial infarction: a population study. Circulation 2011; 124(19): 2073-81.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.025858] [PMID: 22025601]
[34]
Sands-Lincoln M, Loucks EB, Lu B, et al. Sleep duration, insomnia, and coronary heart disease among postmenopausal women in the Women’s Health Initiative. J Womens Health (Larchmt) 2013; 22(6): 477-86.
[http://dx.doi.org/10.1089/jwh.2012.3918] [PMID: 23651054]
[35]
Canivet C, Nilsson PM, Lindeberg SI, Karasek R, Östergren PO. Insomnia increases risk for cardiovascular events in women and in men with low socioeconomic status: a longitudinal, register-based study. J Psychosom Res 2014; 76(4): 292-9.
[http://dx.doi.org/10.1016/j.jpsychores.2014.02.001] [PMID: 24630179]
[36]
Hsu CY, Chen YT, Chen MH, et al. The association between insomnia and increased future cardiovascular events: a nationwide population-based study. Psychosom Med 2015; 77(7): 743-51.
[http://dx.doi.org/10.1097/PSY.0000000000000199] [PMID: 26355726]
[37]
Daghlas I, Dashti HS, Lane J, et al. Sleep duration and myocardial infarction. J Am Coll Cardiol 2019; 74(10): 1304-14.
[http://dx.doi.org/10.1016/j.jacc.2019.07.022] [PMID: 31488267]
[38]
Hublin C, Partinen M, Koskenvuo M, Kaprio J. Sleep and mortality: a population-based 22-year follow-up study. Sleep 2007; 30(10): 1245-53.
[http://dx.doi.org/10.1093/sleep/30.10.1245] [PMID: 17969458]
[39]
Cappuccio FP, Cooper D, D’Elia L, Strazzullo P, Miller MA. Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies. Eur Heart J 2011; 32(12): 1484-92.
[http://dx.doi.org/10.1093/eurheartj/ehr007] [PMID: 21300732]
[40]
Sofi F, Cesari F, Casini A, Macchi C, Abbate R, Gensini GF. Insomnia and risk of cardiovascular disease: a meta-analysis. Eur J Prev Cardiol 2014; 21(1): 57-64.
[http://dx.doi.org/10.1177/2047487312460020] [PMID: 22942213]
[41]
Li M, Zhang XW, Hou WS, Tang ZY. Insomnia and risk of cardiovascular disease: a meta-analysis of cohort studies. Int J Cardiol 2014; 176(3): 1044-7.
[http://dx.doi.org/10.1016/j.ijcard.2014.07.284] [PMID: 25156850]
[42]
Itani O, Jike M, Watanabe N, Kaneita Y. Short sleep duration and health outcomes: a systematic review, meta-analysis, and meta-regression. Sleep Med 2017; 32: 246-56.
[http://dx.doi.org/10.1016/j.sleep.2016.08.006] [PMID: 27743803]
[43]
Jike M, Itani O, Watanabe N, Buysse DJ, Kaneita Y. Long sleep duration and health outcomes: A systematic review, meta-analysis and meta-regression. Sleep Med Rev 2018; 39: 25-36.
[http://dx.doi.org/10.1016/j.smrv.2017.06.011] [PMID: 28890167]
[44]
Lovato N, Lack L. Insomnia and mortality: A meta-analysis. Sleep Med Rev 2019; 43: 71-83.
[http://dx.doi.org/10.1016/j.smrv.2018.10.004] [PMID: 30529432]
[45]
Pepin JL, Borel AL, Tamisier R, Baguet JP, Levy P, Dauvilliers Y. Hypertension and sleep: overview of a tight relationship. Sleep Med Rev 2014; 18(6): 509-19.
[http://dx.doi.org/10.1016/j.smrv.2014.03.003] [PMID: 24846771]
[46]
Gottlieb DJ, Redline S, Nieto FJ, et al. Association of usual sleep duration with hypertension: the sleep heart health study. Sleep 2006; 29(8): 1009-14.
[http://dx.doi.org/10.1093/sleep/29.8.1009] [PMID: 16944668]
[47]
Gangwisch JE, Heymsfield SB, Boden-Albala B, et al. Short sleep duration as a risk factor for hypertension: analyses of the first national health and nutrition examination survey. Hypertension 2006; 47(5): 833-9.
[http://dx.doi.org/10.1161/01.HYP.0000217362.34748.e0] [PMID: 16585410]
[48]
Cappuccio FP, Stranges S, Kandala NB, et al. Gender-specific associations of short sleep duration with prevalent and incident hypertension: the Whitehall II study. Hypertension 2007; 50(4): 693-700.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.095471] [PMID: 17785629]
[49]
Knutson KL, Van Cauter E, Rathouz PJ, et al. Association between sleep and blood pressure in midlife: the CARDIA sleep study. Arch Intern Med 2009; 169(11): 1055-61.
[http://dx.doi.org/10.1001/archinternmed.2009.119] [PMID: 19506175]
[50]
Javaheri S, Storfer-Isser A, Rosen CL, Redline S. Sleep quality and elevated blood pressure in adolescents. Circulation 2008; 118(10): 1034-40.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.108.766410] [PMID: 18711015]
[51]
Bruno RM, Palagini L, Gemignani A, et al. Poor sleep quality and resistant hypertension. Sleep Med 2013; 14(11): 1157-63.
[http://dx.doi.org/10.1016/j.sleep.2013.04.020] [PMID: 23993872]
[52]
Wang Q, Xi B, Liu M, Zhang Y, Fu M. Short sleep duration is associated with hypertension risk among adults: a systematic review and meta-analysis. Hypertens Res 2012; 35(10): 1012-8.
[http://dx.doi.org/10.1038/hr.2012.91] [PMID: 22763475]
[53]
Guo X, Zheng L, Wang J, et al. Epidemiological evidence for the link between sleep duration and high blood pressure: a systematic review and meta-analysis. Sleep Med 2013; 14(4): 324-32.
[http://dx.doi.org/10.1016/j.sleep.2012.12.001] [PMID: 23394772]
[54]
Meng L, Zheng Y, Hui R. The relationship of sleep duration and insomnia to risk of hypertension incidence: a meta-analysis of pro-spective cohort studies. Hypertens Res 2013; 36(11): 985-95.
[http://dx.doi.org/10.1038/hr.2013.70] [PMID: 24005775]
[55]
Wang Y, Mei H, Jiang YR, et al. Relationship between duration of sleep and hypertension in adults: a meta-analysis. J Clin Sleep Med 2015; 11(9): 1047-56.
[http://dx.doi.org/10.5664/jcsm.5024] [PMID: 25902823]
[56]
Laugsand LE, Strand LB, Platou C, Vatten LJ, Janszky I. Insomnia and the risk of incident heart failure: a population study. Eur Heart J 2014; 35(21): 1382-93.
[http://dx.doi.org/10.1093/eurheartj/eht019] [PMID: 23462728]
[57]
Larsson SC, Markus HS. Genetic liability to insomnia and cardiovascular disease risk. Circulation 2019; 140(9): 796-8.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.119.041830] [PMID: 31422675]
[58]
Chimluang J, Aungsuroch Y, Jitpanya C. Descriptors of insomnia among patients with heart failure. J Med Assoc Thai 2017; 100(4): 403-9.
[PMID: 29911836]
[59]
Kanno Y, Yoshihisa A, Watanabe S, et al. Prognostic significance of insomnia in heart failure. Circ J 2016; 80(7): 1571-7.
[http://dx.doi.org/10.1253/circj.CJ-16-0205] [PMID: 27194467]
[60]
Somers VK, White DP, 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. In collaboration with the national heart, lung, and blood institute national center on sleep disorders research (national institutes of health). Circulation 2008; 118(10): 1080-111.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.189420] [PMID: 18725495]
[61]
Christensen MA, Dixit S, Dewland TA, et al. Sleep characteristics that predict atrial fibrillation. Heart Rhythm 2018; 15(9): 1289-95.
[http://dx.doi.org/10.1016/j.hrthm.2018.05.008] [PMID: 29958805]
[62]
Han X, Yang Y, Chen Y, et al. Association between insomnia and atrial fibrillation in a Chinese population: A cross-sectional study. Clin Cardiol 2017; 40(9): 765-9.
[http://dx.doi.org/10.1002/clc.22731] [PMID: 28561943]
[63]
Lee HH, Chen YC, Chen JJ, Lo SH, Guo YL, Hu HY. Insomnia and the risk of atrial fibrillation: a population-based cohort study. Acta Cardiol Sin 2017; 33(2): 165-72.
[PMID: 28344420]
[64]
Chokesuwattanaskul R, Thongprayoon C, Sharma K, Congrete S, Tanawuttiwat T, Cheungpasitporn W. Associations of sleep quality with incident atrial fibrillation: a meta-analysis. Intern Med J 2018; 48(8): 964-72.
[http://dx.doi.org/10.1111/imj.13764] [PMID: 29460411]
[65]
Morovatdar N, Ebrahimi N, Rezaee R, Poorzand H, Bayat Tork MA, Sahebkar A. Sleep duration and risk of atrial fibrillation: a systematic review. J Atr Fibrillation 2019; 11(6): 2132.
[PMID: 31384362]
[66]
Cakici M, Dogan A, Cetin M, et al. Negative effects of acute sleep deprivation on left ventricular functions and cardiac repolarization in healthy young adults. Pacing Clin Electrophysiol 2015; 38(6): 713-22.
[http://dx.doi.org/10.1111/pace.12534] [PMID: 25353305]
[67]
Ozer O, Ozbala B, Sari I, et al. Acute sleep deprivation is associated with increased QT dispersion in healthy young adults. Pacing Clin Electrophysiol 2008; 31(8): 979-84.
[http://dx.doi.org/10.1111/j.1540-8159.2008.01125.x] [PMID: 18684254]
[68]
Miner SE, Pahal D, Nichols L, Darwood A, Nield LE, Wulffhart Z. Sleep disruption is associated with increased ventricular ectopy and cardiac arrest in hospitalized adults. Sleep (Basel) 2016; 39(4): 927-35.
[http://dx.doi.org/10.5665/sleep.5656] [PMID: 26715226]
[69]
Wu MP, Lin HJ, Weng SF, Ho CH, Wang JJ, Hsu YW. Insomnia subtypes and the subsequent risks of stroke: report from a nationally representative cohort. Stroke 2014; 45(5): 1349-54.
[http://dx.doi.org/10.1161/STROKEAHA.113.003675] [PMID: 24699057]
[70]
He Q, Zhang P, Li G, Dai H, Shi J. The association between insomnia symptoms and risk of cardio-cerebral vascular events: A meta-analysis of prospective cohort studies. Eur J Prev Cardiol 2017; 24(10): 1071-82.
[http://dx.doi.org/10.1177/2047487317702043] [PMID: 28359160]
[71]
van der Pal KC, Koopman ADM, Lakerveld J, et al. The association between multiple sleep-related characteristics and the metabolic syndrome in the general population: the New Hoorn study. Sleep Med 2018; 52: 51-7.
[http://dx.doi.org/10.1016/j.sleep.2018.07.022] [PMID: 30278295]
[72]
Gaston SA, Park YM, McWhorter KL, Sandler DP, Jackson CL. Multiple poor sleep characteristics and metabolic abnormalities consistent with metabolic syndrome among white, black, and Hispanic/Latina women: modification by menopausal status. Diabetol Metab Syndr 2019; 11: 17.
[http://dx.doi.org/10.1186/s13098-019-0413-2] [PMID: 30815038]
[73]
Akbaraly TN, Jaussent I, Besset A, et al. Sleep complaints and metabolic syndrome in an elderly population: the three-city study. Am J Geriatr Psychiatry 2015; 23(8): 818-28.
[http://dx.doi.org/10.1016/j.jagp.2014.10.001] [PMID: 25499672]
[74]
Rosique-Esteban N, Papandreou C, Romaguera D, et al. Cross-sectional associations of objectively-measured sleep characteristics with obesity and type 2 diabetes in the PREDIMED-Plus trial. Sleep (Basel) 2018; 41(12)
[http://dx.doi.org/10.1093/sleep/zsy190] [PMID: 30285250]
[75]
Zuraikat FM, Makarem N, Liao M, St-Onge MP, Aggarwal B. Measures of poor sleep quality are associated with higher energy intake and poor diet quality in a diverse sample of women from the go red for women strategically focused research network. J Am Heart Assoc 2020; 9(4)e014587
[http://dx.doi.org/10.1161/JAHA.119.014587] [PMID: 32063123]
[76]
Costemale-Lacoste JF, Asmar KE, Rigal A, et al. Severe insomnia is associated with metabolic syndrome in women over 50 years with major depression treated in psychiatry settings: a METADAP report. J Affect Disord 2020; 264: 513-8.
[http://dx.doi.org/10.1016/j.jad.2019.11.084] [PMID: 32056777]
[77]
Countryman AJ, Saab PG, Llabre MM, Penedo FJ, McCalla JR, Schneiderman N. Cardiometabolic risk in adolescents: associations with physical activity, fitness, and sleep. Ann Behav Med 2013; 45(1): 121-31.
[http://dx.doi.org/10.1007/s12160-012-9428-8] [PMID: 23080394]
[78]
Vgontzas AN, Bixler EO, Lin HM, et al. Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications. J Clin Endocrinol Metab 2001; 86(8): 3787-94.
[http://dx.doi.org/10.1210/jcem.86.8.7778] [PMID: 11502812]
[79]
Perlis M, Pigeon W, Gehrman P, Findley J, Drummond S. Neurobiological mechanisms in chronic insomnia. Sleep Med Clin 2009; 4(4): 549-58.
[http://dx.doi.org/10.1016/j.jsmc.2009.07.002] [PMID: 30983923]
[80]
Kalmbach DA, Anderson JR, Drake CL. The impact of stress on sleep: Pathogenic sleep reactivity as a vulnerability to insomnia and circadian disorders. J Sleep Res 2018; 27(6)e12710
[http://dx.doi.org/10.1111/jsr.12710] [PMID: 29797753]
[81]
Min JY, Min KB. Outdoor artificial nighttime light and use of hypnotic medications in older adults: a population-based cohort study. J Clin Sleep Med 2018; 14(11): 1903-10.
[http://dx.doi.org/10.5664/jcsm.7490] [PMID: 30373695]
[82]
Costa G. Sleep deprivation due to shift work. Handb Clin Neurol 2015; 131: 437-46.
[http://dx.doi.org/10.1016/B978-0-444-62627-1.00023-8] [PMID: 26563802]
[83]
Trinder J, Kleiman J, Carrington M, et al. Autonomic activity during human sleep as a function of time and sleep stage. J Sleep Res 2001; 10(4): 253-64.
[http://dx.doi.org/10.1046/j.1365-2869.2001.00263.x] [PMID: 11903855]
[84]
Somers VK, Dyken ME, Mark AL, Abboud FM. Sympathetic-nerve activity during sleep in normal subjects. N Engl J Med 1993; 328(5): 303-7.
[http://dx.doi.org/10.1056/NEJM199302043280502] [PMID: 8419815]
[85]
Tobaldini E, Fiorelli EM, Solbiati M, Costantino G, Nobili L, Montano N. Short sleep duration and cardiometabolic risk: from patho-physiology to clinical evidence. Nat Rev Cardiol 2019; 16(4): 213-24.
[http://dx.doi.org/10.1038/s41569-018-0109-6] [PMID: 30410106]
[86]
Grimaldi D, Goldstein MR, Carter JR. Insomnia and cardiovascular autonomic control. Auton Neurosci 2019; 220102551
[http://dx.doi.org/10.1016/j.autneu.2019.05.003] [PMID: 31331688]
[87]
Fink AM, Bronas UG, Calik MW. Autonomic regulation during sleep and wakefulness: a review with implications for defining the pathophysiology of neurological disorders. Clin Auton Res 2018; 28(6): 509-18.
[http://dx.doi.org/10.1007/s10286-018-0560-9] [PMID: 30155794]
[88]
Vgontzas AN, Fernandez-Mendoza J, Liao D, Bixler EO. Insomnia with objective short sleep duration: the most biologically severe phenotype of the disorder. Sleep Med Rev 2013; 17(4): 241-54.
[http://dx.doi.org/10.1016/j.smrv.2012.09.005] [PMID: 23419741]
[89]
Sauvet F, Florence G, Van Beers P, et al. Total sleep deprivation alters endothelial function in rats: a nonsympathetic mechanism. Sleep (Basel) 2014; 37(3): 465-73.
[http://dx.doi.org/10.5665/sleep.3476] [PMID: 24587568]
[90]
Mullington JM, Simpson NS, Meier-Ewert HK, Haack M. Sleep loss and inflammation. Best Pract Res Clin Endocrinol Metab 2010; 24(5): 775-84.
[http://dx.doi.org/10.1016/j.beem.2010.08.014] [PMID: 21112025]
[91]
Irwin MR, Olmstead R, Carrillo C, et al. Cognitive behavioral therapy vs. Tai Chi for late life insomnia and inflammatory risk: a randomized controlled comparative efficacy trial. Sleep (Basel) 2014; 37(9): 1543-52.
[http://dx.doi.org/10.5665/sleep.4008] [PMID: 25142571]
[92]
Irwin MR, Olmstead R, Carroll JE. Sleep disturbance, sleep duration, and inflammation: a systematic review and meta-analysis of cohort studies and experimental sleep deprivation. Biol Psychiatry 2016; 80(1): 40-52.
[http://dx.doi.org/10.1016/j.biopsych.2015.05.014] [PMID: 26140821]
[93]
Liu R, Liu X, Zee PC, et al. Association between sleep quality and C-reactive protein: results from national health and nutrition exami-nation survey, 2005-2008. PLoS One 2014; 9(3)e92607
[http://dx.doi.org/10.1371/journal.pone.0092607] [PMID: 24663098]
[94]
Gulec M, Ozkol H, Selvi Y, et al. Oxidative stress in patients with primary insomnia. Prog Neuropsychopharmacol Biol Psychiatry 2012; 37(2): 247-51.
[http://dx.doi.org/10.1016/j.pnpbp.2012.02.011] [PMID: 22401887]
[95]
Liang B, Li YH, Kong H. Serum paraoxonase, arylesterase activities and oxidative status in patients with insomnia. Eur Rev Med Pharmacol Sci 2013; 17(18): 2517-22.
[PMID: 24089233]
[96]
Belcaro G, Saggino A, Cornelli U, et al. Improvement in mood, oxidative stress, fatigue, and insomnia following supplementary management with Robuvit®. J Neurosurg Sci 2018; 62(4): 423-7.
[PMID: 29938480]
[97]
Kanagasabai T, Ardern CI. Inflammation, oxidative stress, and antioxidants contribute to selected sleep quality and cardiometabolic health relationships: a cross-sectional study. Mediators Inflamm 2015; 2015824589
[http://dx.doi.org/10.1155/2015/824589] [PMID: 26568665]
[98]
De Lorenzo BH, de Oliveira Marchioro L, Greco CR, Suchecki D. Sleep-deprivation reduces NK cell number and function mediated by β-adrenergic signalling. Psychoneuroendocrinology 2015; 57: 134-43.
[http://dx.doi.org/10.1016/j.psyneuen.2015.04.006] [PMID: 25929826]
[99]
Yehuda S, Sredni B, Carasso RL, Kenigsbuch-Sredni D. REM sleep deprivation in rats results in inflammation and interleukin-17 elevation. J Interferon Cytokine Res 2009; 29(7): 393-8.
[http://dx.doi.org/10.1089/jir.2008.0080] [PMID: 19450150]
[100]
Fondell E, Axelsson J, Franck K, et al. Short natural sleep is associated with higher T cell and lower NK cell activities. Brain Behav Immun 2011; 25(7): 1367-75.
[http://dx.doi.org/10.1016/j.bbi.2011.04.004] [PMID: 21496482]
[101]
McAlpine CS, Kiss MG, Rattik S, et al. Sleep modulates haematopoiesis and protects against atherosclerosis. Nature 2019; 566(7744): 383-7.
[http://dx.doi.org/10.1038/s41586-019-0948-2] [PMID: 30760925]
[102]
Kornum BR, Knudsen S, Ollila HM, et al. Narcolepsy. Nat Rev Dis Primers 2017; 3: 16100.
[http://dx.doi.org/10.1038/nrdp.2016.100] [PMID: 28179647]
[103]
Hammerschlag AR, Stringer S, de Leeuw CA, et al. Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits. Nat Genet 2017; 49(11): 1584-92.
[http://dx.doi.org/10.1038/ng.3888] [PMID: 28604731]
[104]
Li Y, Hao Y, Fan F, Zhang B. The role of microbiome in insomnia, circadian disturbance and depression. Front Psychiatry 2018; 9: 669.
[http://dx.doi.org/10.3389/fpsyt.2018.00669] [PMID: 30568608]
[105]
Liu B, Lin W, Chen S, et al. Gut microbiota as a subjective measurement for auxiliary diagnosis of insomnia disorder. Front Microbiol 2019; 10: 1770.
[http://dx.doi.org/10.3389/fmicb.2019.01770] [PMID: 31456757]
[106]
Larsen N, Vogensen FK, van den Berg FW, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 2010; 5(2)e9085
[http://dx.doi.org/10.1371/journal.pone.0009085] [PMID: 20140211]
[107]
Adnan S, Nelson JW, Ajami NJ, et al. Alterations in the gut microbiota can elicit hypertension in rats. Physiol Genomics 2017; 49(2): 96-104.
[http://dx.doi.org/10.1152/physiolgenomics.00081.2016] [PMID: 28011881]
[108]
Tang WH, Kitai T, Hazen SL. Gut microbiota in cardiovascular health and disease. Circ Res 2017; 120(7): 1183-96.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.309715] [PMID: 28360349]
[109]
Sun L, Ma L, Ma Y, Zhang F, Zhao C, Nie Y. Insights into the role of gut microbiota in obesity: pathogenesis, mechanisms, and therapeutic perspectives. Protein Cell 2018; 9(5): 397-403.
[http://dx.doi.org/10.1007/s13238-018-0546-3] [PMID: 29725936]
[110]
Ahmad AF, Dwivedi G, O’Gara F, Caparros-Martin J, Ward NC. The gut microbiome and cardiovascular disease: current knowledge and clinical potential. Am J Physiol Heart Circ Physiol 2019; 317(5): H923-38.
[http://dx.doi.org/10.1152/ajpheart.00376.2019] [PMID: 31469291]
[111]
Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444(7122): 1027-31.
[http://dx.doi.org/10.1038/nature05414] [PMID: 17183312]
[112]
Koliada A, Syzenko G, Moseiko V, et al. Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population. BMC Microbiol 2017; 17(1): 120.
[http://dx.doi.org/10.1186/s12866-017-1027-1] [PMID: 28532414]
[113]
Clarke SF, Murphy EF, O’Sullivan O, et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut 2014; 63(12): 1913-20.
[http://dx.doi.org/10.1136/gutjnl-2013-306541] [PMID: 25021423]
[114]
Kristensen NB, Bryrup T, Allin KH, Nielsen T, Hansen TH, Pedersen O. Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: a systematic review of randomized controlled trials. Genome Med 2016; 8(1): 52.
[http://dx.doi.org/10.1186/s13073-016-0300-5] [PMID: 27159972]
[115]
Riemann D, Baglioni C, Bassetti C, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res 2017; 26(6): 675-700.
[http://dx.doi.org/10.1111/jsr.12594] [PMID: 28875581]
[116]
Kay-Stacey M, Attarian H. Advances in the management of chronic insomnia. BMJ 2016; 354: i2123.
[http://dx.doi.org/10.1136/bmj.i2123] [PMID: 27383400]
[117]
Wu JQ, Appleman ER, Salazar RD, Ong JC. Cognitive behavioral therapy for insomnia comorbid with psychiatric and medical conditions: a meta-analysis. JAMA Intern Med 2015; 175(9): 1461-72.
[http://dx.doi.org/10.1001/jamainternmed.2015.3006] [PMID: 26147487]
[118]
Heenan A, Pipe A, Lemay K, Davidson JR, Tulloch H. Cognitive-behavioral therapy for insomnia tailored to patients with cardiovascular disease: a pre-post study. Behav Sleep Med 2020; 18(3): 372-85.
[http://dx.doi.org/10.1080/15402002.2019.1594815] [PMID: 31007057]
[119]
Redeker NS, Jeon S, Andrews L, Cline J, Jacoby D, Mohsenin V. Feasibility and efficacy of a self-management intervention for insomnia in stable heart failure. J Clin Sleep Med 2015; 11(10): 1109-19.
[http://dx.doi.org/10.5664/jcsm.5082] [PMID: 25979100]
[120]
Redeker NS, Jeon S, Andrews L, Cline J, Mohsenin V, Jacoby D. Effects of cognitive behavioral therapy for insomnia on sleep-related cognitions among patients with stable heart failure. Behav Sleep Med 2019; 17(3): 342-54.
[http://dx.doi.org/10.1080/15402002.2017.1357120] [PMID: 28745520]
[121]
Manolis AS, Manolis AA. Exercise and arrhythmias: a double-edged sword. Pacing Clin Electrophysiol 2016; 39(7): 748-62.
[http://dx.doi.org/10.1111/pace.12879] [PMID: 27120033]
[122]
Lowe H, Haddock G, Mulligan LD, et al. Does exercise improve sleep for adults with insomnia? A systematic review with quality appraisal. Clin Psychol Rev 2019; 68: 1-12.
[http://dx.doi.org/10.1016/j.cpr.2018.11.002] [PMID: 30617012]
[123]
Kuriyama A, Tabata H. Suvorexant for the treatment of primary insomnia: A systematic review and meta-analysis. Sleep Med Rev 2017; 35: 1-7.
[http://dx.doi.org/10.1016/j.smrv.2016.09.004] [PMID: 28365447]
[124]
Garg H. Role of optimum diagnosis and treatment of insomnia in patients with hypertension and diabetes: A review. J Family Med Prim Care 2018; 7(5): 876-83.
[PMID: 30598926]
[125]
Kim YH, Kim HB, Kim DH, Kim JY, Shin HY. Use of hypnotics and the risk of or mortality from heart disease: a meta-analysis of observational studies. Korean J Intern Med (Korean Assoc Intern Med) 2018; 33(4): 727-36.
[http://dx.doi.org/10.3904/kjim.2016.282] [PMID: 28844123]
[126]
Weich S, Pearce HL, Croft P, et al. Effect of anxiolytic and hypnotic drug prescriptions on mortality hazards: retrospective cohort study. BMJ 2014; 348: g1996.
[http://dx.doi.org/10.1136/bmj.g1996] [PMID: 24647164]
[127]
Parsaik AK, Mascarenhas SS, Khosh-Chashm D, et al. Mortality associated with anxiolytic and hypnotic drugs-A systematic review and meta-analysis. Aust N Z J Psychiatry 2016; 50(6): 520-33.
[http://dx.doi.org/10.1177/0004867415616695] [PMID: 26590022]
[128]
Mesrine S, Gusto G, Clavel-Chapelon F, Boutron-Ruault MC, Fournier A. Use of benzodiazepines and cardiovascular mortality in a cohort of women aged over 50 years. Eur J Clin Pharmacol 2018; 74(11): 1475-84.
[http://dx.doi.org/10.1007/s00228-018-2515-4] [PMID: 29971451]
[129]
Lan TY, Zeng YF, Tang GJ, et al. The use of hypnotics and mortality--a population-based retrospective cohort study. PLoS One 2015; 10(12)e0145271
[http://dx.doi.org/10.1371/journal.pone.0145271] [PMID: 26709926]
[130]
Gulliksson M, Burell G, Vessby B, Lundin L, Toss H, Svärdsudd K. Randomized controlled trial of cognitive behavioral therapy vs. standard treatment to prevent recurrent cardiovascular events in patients with coronary heart disease: Secondary Prevention in Uppsala Primary Health Care project (SUPRIM). Arch Intern Med 2011; 171(2): 134-40.
[http://dx.doi.org/10.1001/archinternmed.2010.510] [PMID: 21263103]
[131]
Dekker RL, Moser DK, Peden AR, Lennie TA. Cognitive therapy improves three-month outcomes in hospitalized patients with heart failure. J Card Fail 2012; 18(1): 10-20.
[http://dx.doi.org/10.1016/j.cardfail.2011.09.008] [PMID: 22196836]
[132]
Conley S, Redeker NS. Cognitive behavioral therapy for insomnia in the context of cardiovascular conditions. Curr Sleep Med Rep 2015; 1(3): 157-65.
[http://dx.doi.org/10.1007/s40675-015-0019-7] [PMID: 26500835]
[133]
Castro-Diehl C, Wood AC, Redline S, et al. Mediterranean diet pattern and sleep duration and insomnia symptoms in the Multi-Ethnic Study of Atherosclerosis. Sleep (Basel) 2018; 41(11): 158.
[http://dx.doi.org/10.1093/sleep/zsy158] [PMID: 30137563]
[134]
Salas-Salvadó J, Becerra-Tomás N, García-Gavilán JF, Bulló M, Barrubés L. Mediterranean diet and cardiovascular disease prevention: what do we know? Prog Cardiovasc Dis 2018; 61(1): 62-7.
[http://dx.doi.org/10.1016/j.pcad.2018.04.006] [PMID: 29678447]
[135]
Watson NF, Badr MS, Belenky G, et al. Recommended amount of sleep for a healthy adult: a joint consensus statement of the american academy of sleep medicine and sleep research society. Sleep (Basel) 2015; 38(6): 843-4.
[http://dx.doi.org/10.5665/sleep.4716] [PMID: 26039963]
[136]
Kwok CS, Kontopantelis E, Kuligowski G, et al. Self-reported sleep duration and quality and cardiovascular disease and mortality: a dose-response meta-analysis. J Am Heart Assoc 2018; 7(15)e008552
[http://dx.doi.org/10.1161/JAHA.118.008552] [PMID: 30371228]
[137]
Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD. Management of chronic insomnia disorder in adults: a clinical practice guideline from the American college of physicians. Ann Intern Med 2016; 165(2): 125-33.
[http://dx.doi.org/10.7326/M15-2175] [PMID: 27136449]
[138]
Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American academy of sleep medicine clinical practice guideline. J Clin Sleep Med 2017; 13(2): 307-49.
[http://dx.doi.org/10.5664/jcsm.6470] [PMID: 27998379]
[139]
Mantua J, Spencer RMC. Exploring the nap paradox: are mid-day sleep bouts a friend or foe? Sleep Med 2017; 37: 88-97.
[http://dx.doi.org/10.1016/j.sleep.2017.01.019] [PMID: 28899546]
[140]
Naska A, Oikonomou E, Trichopoulou A, Psaltopoulou T, Trichopoulos D. Siesta in healthy adults and coronary mortality in the general population. Arch Intern Med 2007; 167(3): 296-301.
[http://dx.doi.org/10.1001/archinte.167.3.296] [PMID: 17296887]
[141]
Zaregarizi M, Edwards B, George K, Harrison Y, Jones H, Atkinson . G. Acute changes in cardiovascular function during the onset period of daytime sleep: comparison to lying awake and standing. J Appl Physiol (1985) 2007; 103(4): 1332-8.
[142]
Stang A, Dragano N, Poole C, et al. Daily siesta, cardiovascular risk factors, and measures of subclinical atherosclerosis: results of the Heinz Nixdorf recall study. Sleep 2007; 30(9): 1111-9.
[http://dx.doi.org/10.1093/sleep/30.9.1111] [PMID: 17910383]
[143]
Masa JF, Rubio M, Pérez P, Mota M, de Cos JS, Montserrat JM. Association between habitual naps and sleep apnea. Sleep 2006; 29(11): 1463-8.
[http://dx.doi.org/10.1093/sleep/29.11.1463] [PMID: 17162994]
[144]
Bursztyn M, Ginsberg G, Hammerman-Rozenberg R, Stessman J. The siesta in the elderly: risk factor for mortality? Arch Intern Med 1999; 159(14): 1582-6.
[http://dx.doi.org/10.1001/archinte.159.14.1582] [PMID: 10421281]
[145]
Campos H, Siles X. Siesta and the risk of coronary heart disease: results from a population-based, case-control study in Costa Rica. Int J Epidemiol 2000; 29(3): 429-37.
[http://dx.doi.org/10.1093/ije/29.3.429] [PMID: 10869314]
[146]
Leng Y, Wainwright NW, Cappuccio FP, et al. Daytime napping and the risk of all-cause and cause-specific mortality: a 13-year follow-up of a British population. Am J Epidemiol 2014; 179(9): 1115-24.
[http://dx.doi.org/10.1093/aje/kwu036] [PMID: 24685532]
[147]
Yan B, Li J, Li R, Gao Y, Zhang J, Wang G. Association of daytime napping with incident cardiovascular disease in a community-based population. Sleep Med 2019; 57: 128-34.
[http://dx.doi.org/10.1016/j.sleep.2019.02.014] [PMID: 30981956]
[148]
Lin D, Sun K, Li F, et al. Association between habitual daytime napping and metabolic syndrome: a population-based study. Metabolism 2014; 63(12): 1520-7.
[http://dx.doi.org/10.1016/j.metabol.2014.08.005] [PMID: 25249445]
[149]
O’Brien E, Kario K, Staessen JA, de la Sierra A, Ohkubo T. Patterns of ambulatory blood pressure: clinical relevance and application. J Clin Hypertens (Greenwich) 2018; 20(7): 1112-5.
[http://dx.doi.org/10.1111/jch.13277] [PMID: 30003696]
[150]
Mulcahy D, Wright C, Sparrow J, et al. Heart rate and blood pressure consequences of an afternoon SIESTA (Snooze-Induced Excitation of Sympathetic Triggered Activity). Am J Cardiol 1993; 71(7): 611-4.
[http://dx.doi.org/10.1016/0002-9149(93)90524-G] [PMID: 8438754]
[151]
Bursztyn M, Mekler J, Ben-Ishay D. The siesta and ambulatory blood pressure: is waking up the same in the morning and afternoon? J Hum Hypertens 1996; 10(5): 287-92.
[PMID: 8817401]
[152]
Wang C, Bangdiwala SI, Rangarajan S, et al. Association of estimated sleep duration and naps with mortality and cardiovascular events: a study of 116632 people from 21 countries. Eur Heart J 2019; 40(20): 1620-9.
[http://dx.doi.org/10.1093/eurheartj/ehy695] [PMID: 30517670]
[153]
Hossin MZ. From habitual sleep hours to morbidity and mortality: existing evidence, potential mechanisms, and future agenda. Sleep Health 2016; 2(2): 146-53.
[http://dx.doi.org/10.1016/j.sleh.2016.01.006] [PMID: 28923258]
[154]
Sabanayagam C, Shankar A. Sleep duration and cardiovascular disease: results from the National Health Interview Survey. Sleep 2010; 33(8): 1037-42.
[http://dx.doi.org/10.1093/sleep/33.8.1037] [PMID: 20815184]
[155]
Yamada T, Hara K, Shojima N, Yamauchi T, Kadowaki T. Daytime napping and the risk of cardiovascular disease and all-cause mortality: a prospective study and dose-response meta-analysis. Sleep (Basel) 2015; 38(12): 1945-53.
[http://dx.doi.org/10.5665/sleep.5246] [PMID: 26158892]
[156]
Manolis AS, Manolis AA. Premature heart disease mortality: A sobering reality calling for action. Trends Cardiovasc Med 2020; 30(6): 375-7.
[http://dx.doi.org/10.1016/j.tcm.2019.09.008]
[157]
Fan M, Sun D, Zhou T, et al. Sleep patterns, genetic susceptibility, and incident cardiovascular disease: a prospective study of 385 292 UK biobank participants. Eur Heart J 2019; 41(11): 1182-9.
[http://dx.doi.org/10.1093/eurheartj/ehz849] [PMID: 31848595]
[158]
Yu J, Zhou Z, McEvoy RD, et al. Association of positive airway pressure with cardiovascular events and death in adults with sleep apnea: a systematic review and meta-analysis. JAMA 2017; 318(2): 156-66.
[http://dx.doi.org/10.1001/jama.2017.7967] [PMID: 28697252]
[159]
Redline S, Foody J. Sleep disturbances: time to join the top 10 potentially modifiable cardiovascular risk factors? Circulation 2011; 124(19): 2049-51.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.062190] [PMID: 22064955]
[160]
Kempf A, Song SM, Talbot CB, Miesenböck G. A potassium channel β-subunit couples mitochondrial electron transport to sleep. Nature 2019; 568(7751): 230-4.
[http://dx.doi.org/10.1038/s41586-019-1034-5] [PMID: 30894743]

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