{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:41:01Z","timestamp":1792636861821,"version":"4.5.0"},"reference-count":65,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Adverse cardiovascular events occur more frequently in the morning than at other times of the day. Vascular endothelial function (VEF)\u2014a robust cardiovascular risk marker\u2014is impaired during this morning period. We recently discovered that this morning impairment in VEF is not caused by either overnight sleep or the inactivity that accompanies sleep. We determined whether the endogenous circadian system is responsible for this morning impairment in VEF. We also assessed whether the circadian system affects mechanistic biomarkers, that is, oxidative stress (malondialdehyde adducts), endothelin-1, blood pressure, and heart rate.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Twenty-one (11 women) middle-aged healthy participants completed a 5-day laboratory protocol in dim light where all behaviors, including sleep and activity, and all physiological measurements were evenly distributed across the 24-hour period. After baseline testing, participants underwent 10 recurring 5-hour 20-minute behavioral cycles of 2-hour 40-minute sleep opportunities and 2 hours and 40 minutes of standardized waking episodes. VEF, blood pressure, and heart rate were measured, and venous blood was sampled immediately after awakening during each wake episode. Independent of behaviors, VEF was significantly attenuated during the subjective night and across the morning (\n              <jats:italic>P<\/jats:italic>\n              =0.04). Malondialdehyde adducts and endothelin-1 exhibited circadian rhythms with increases across the morning vulnerable period and peaks around noon (\n              <jats:italic>P<\/jats:italic>\n              \u22640.01). Both systolic (\n              <jats:italic>P<\/jats:italic>\n              =0.005) and diastolic blood pressure (\n              <jats:italic>P<\/jats:italic>\n              =0.04) were rhythmic with peaks in the late afternoon.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>The endogenous circadian system impairs VEF and increases malondialdehyde adducts and endothelin-1 in the morning vulnerable hours and may increase the risk of morning adverse cardiovascular events in susceptible individuals.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration\u2014<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifier: NCT02202811.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.119.312682","type":"journal-article","created":{"date-parts":[[2019,4,18]],"date-time":"2019-04-18T09:02:07Z","timestamp":1555578127000},"page":"1203-1211","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":67,"title":["Circadian Rhythm of Vascular Function in Midlife Adults"],"prefix":"10.1161","volume":"39","author":[{"given":"Saurabh S.","family":"Thosar","sequence":"first","affiliation":[{"name":"From the Oregon Institute of Occupational Health Sciences (S.S.T., A.M.B., M.X.H., A.W.M., N.P.B., N.A.C., M.P.B., J.S.E., S.A.S.), Oregon Health &amp; Science University, Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alec M.","family":"Berman","sequence":"additional","affiliation":[{"name":"From the Oregon Institute of Occupational Health Sciences (S.S.T., A.M.B., M.X.H., A.W.M., N.P.B., N.A.C., M.P.B., J.S.E., S.A.S.), Oregon Health &amp; Science University, Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya X.","family":"Herzig","sequence":"additional","affiliation":[{"name":"From the Oregon Institute of Occupational Health Sciences (S.S.T., A.M.B., M.X.H., A.W.M., N.P.B., N.A.C., M.P.B., J.S.E., S.A.S.), Oregon Health &amp; Science University, Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"McHill","sequence":"additional","affiliation":[{"name":"From the Oregon Institute of Occupational Health Sciences (S.S.T., A.M.B., M.X.H., A.W.M., N.P.B., N.A.C., M.P.B., J.S.E., S.A.S.), Oregon Health &amp; Science University, Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole P.","family":"Bowles","sequence":"additional","affiliation":[{"name":"From the Oregon Institute of Occupational Health Sciences (S.S.T., A.M.B., M.X.H., A.W.M., N.P.B., N.A.C., M.P.B., J.S.E., S.A.S.), Oregon Health &amp; Science University, Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Swanson","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Diabetes, University of Colorado School of Medicine, Aurora (C.M.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noal A.","family":"Clemons","sequence":"additional","affiliation":[{"name":"From the Oregon Institute of Occupational Health Sciences (S.S.T., A.M.B., M.X.H., A.W.M., N.P.B., N.A.C., M.P.B., J.S.E., S.A.S.), Oregon Health &amp; Science University, Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Butler","sequence":"additional","affiliation":[{"name":"From the Oregon Institute of Occupational Health Sciences (S.S.T., A.M.B., M.X.H., A.W.M., N.P.B., N.A.C., M.P.B., J.S.E., S.A.S.), Oregon Health &amp; Science University, Portland"},{"name":"Department of Behavioral Neuroscience (M.P.B.), Oregon Health &amp; Science University, Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron A.","family":"Clemons","sequence":"additional","affiliation":[{"name":"Oregon Clinical and Translational Research Institute (A.A.C.), Oregon Health &amp; Science University, Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan S.","family":"Emens","sequence":"additional","affiliation":[{"name":"From the Oregon Institute of Occupational Health Sciences (S.S.T., A.M.B., M.X.H., A.W.M., N.P.B., N.A.C., M.P.B., J.S.E., S.A.S.), Oregon Health &amp; Science University, Portland"},{"name":"Portland Veterans Affairs Medical Center, OR (J.S.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Shea","sequence":"additional","affiliation":[{"name":"From the Oregon Institute of Occupational Health Sciences (S.S.T., A.M.B., M.X.H., A.W.M., N.P.B., N.A.C., M.P.B., J.S.E., S.A.S.), Oregon Health &amp; Science University, Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(92)91391-G"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(98)00278-7"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.75.1.131"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006749107"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-517060"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(95)00327-4"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2012.09.047"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.3109\/07420528.2012.654554"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2008005000012"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000128207.26863.C4"},{"key":"e_1_3_5_12_2","first-page":"227","article-title":"Circadian variation of endothelium-dependent vasodilatation of the brachial artery as a confounding factor in the evaluation of endothelial function.","volume":"149","author":"Gaenzer H","year":"2000","unstructured":"Gaenzer, H, Sturm, W, Kirchmair, R, Neumayr, G, Ritsch, A, Patsch, J. Circadian variation of endothelium-dependent vasodilatation of the brachial artery as a confounding factor in the evaluation of endothelial function. Atherosclerosis. 2000;149:227\u2013228.","journal-title":"Atherosclerosis"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2014.02.001"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00143.2018"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/288373a0"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/332411a0"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00689.2008"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00442.2009"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000269183.13937.e8"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2007.06.004"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.233668"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00314.2018"},{"key":"e_1_3_5_23_2","volume-title":"Sleep and Wakefulness as Alternating Phases in the Cycle of Existence","author":"Kleitman N","year":"1939","unstructured":"Kleitman, N. Sleep and Wakefulness as Alternating Phases in the Cycle of Existence. Chicago: University of Chicago Press, 1939."},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5423.2177"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90841-9"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2869.1992.tb00021.x"},{"issue":"4","key":"e_1_3_5_27_2","first-page":"R1152","article-title":"Circadian temperature and melatonin rhythms, sleep, and neurobehavioral function in humans living on a 20-h day.","volume":"277","author":"Wyatt JK","year":"1999","unstructured":"Wyatt, JK, Ritz-De Cecco, A, Czeisler, CA, Dijk, DJ. Circadian temperature and melatonin rhythms, sleep, and neurobehavioral function in humans living on a 20-h day. Am J Physiol. 1999;277(4 pt 2):R1152\u2013R1163.","journal-title":"Am J Physiol"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010666108"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80590"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2869.1992.tb00004.x"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.227892"},{"key":"e_1_3_5_32_2","first-page":"307","article-title":"The effects of training on heart rate; a longitudinal study.","volume":"35","author":"Karvonen MJ","year":"1957","unstructured":"Karvonen, MJ, Kentala, E, Mustala, O. The effects of training on heart rate; a longitudinal study. Ann Med Exp Biol Fenn. 1957;35:307\u2013315.","journal-title":"Ann Med Exp Biol Fenn"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00471.2010"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.01.049"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq401"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(82)90403-3"},{"key":"e_1_3_5_37_2","volume-title":"The AASM Manual for the Scoring of Sleep and Associated events: Rules, Terminology and Technical Specifications","author":"Iber C","year":"2007","unstructured":"Iber, C, Ancoli-Israel, S, Chesson, A, Quan SftAAoSM. The AASM Manual for the Scoring of Sleep and Associated events: Rules, Terminology and Technical Specifications. 1st ed. Westchester, IL: American Academy of Sleep Medicine; 2007.","edition":"1"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.27083"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.943019"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1177\/0748730408318081"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2009.08.022"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.5166"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200103001-00005"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198706113162405"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(88)90669-8"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199110033251402"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024549"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1177\/174182679500200602"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc4601.099485"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1081\/CBI-120002914"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1139\/Y10-046"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2009.28595"},{"key":"e_1_3_5_53_2","first-page":"1044","article-title":"Weight loss reduces plasma endothelin-1 concentration in obese men.","volume":"231","author":"Maeda S","year":"2006","unstructured":"Maeda, S, Jesmin, S, Iemitsu, M, Otsuki, T, Matsuo, T, Ohkawara, K, Nakata, Y, Tanaka, K, Goto, K, Miyauchi, T. Weight loss reduces plasma endothelin-1 concentration in obese men. Exp Biol Med (Maywood). 2006;231:1044\u20131047.","journal-title":"Exp Biol Med (Maywood)"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.11.015"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.83.2.469"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000198541.12640.0f"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.23.7.1014"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-56-6-1278"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(89)90178-9"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(86)90146-6"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.81.7.8675562"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.04.027"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00404.2009"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.653303"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063347"},{"key":"e_1_3_5_66_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808180106"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.119.312682","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:02:38Z","timestamp":1715554958000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.119.312682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6]]},"references-count":65,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1161\/ATVBAHA.119.312682"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.119.312682","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6]]},"assertion":[{"value":"2019-01-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}