Circadian Rhythm of Vascular Function in Midlife Adults

Abstract

Objective— Adverse cardiovascular events occur more frequently in the morning than at other times of the day. Vascular endothelial function (VEF)—a robust cardiovascular risk marker—is 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. Approach and Results— 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 ( P =0.04). Malondialdehyde adducts and endothelin-1 exhibited circadian rhythms with increases across the morning vulnerable period and peaks around noon ( P ≤0.01). Both systolic ( P =0.005) and diastolic blood pressure ( P =0.04) were rhythmic with peaks in the late afternoon. Conclusions— 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. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02202811.

Sleep Efficiency is Inversely Associated with Brachial Artery Diameter and Morning Blood Pressure in Midlife Adults, with a Potential Sex-Effect

“…We have previously published limited circadian data from these studies. 19 , 34 Volunteers were recruited using flyers on campus, internet research recruitment websites, and word of mouth.…”

“…FMD of the dominant brachial artery was measured using established guidelines after the above measurements and after at least 20 minutes in a supine resting condition and as performed previously. 19 , 20 , 37 A 5×84 cm automatic blood pressure cuff (E-20 rapid cuff inflator; D.E. Hokanson, Bellevue, Wash., USA) was placed on the dominant forearm.…”

“…FMD has a time-of-day variation driven by the circadian system, with low FMD in the morning and a recovery by noon -a difference of nearly 75% between 6 AM and 11 AM. [18][19][20] The timing of the morning minimum in FMD also corresponds to the time window of increased frequency in major adverse CV events. 21,22 There is also evidence that baseline diameter measured as part of FMD is positively associated with CV risk.…”

Effect of Morning vs. Evening Turmeric Consumption on Urine Oxidative Stress Biomarkers in Obese, Middle-Aged Adults: A Feasibility Study

“…Morning (7:00 A.M.) and evening (6:00 P.M.) were chosen as the test food administration clock times, based on findings that circadian rhythms in many physiological systems such as gene expression occur according to the day-night cycle [23]. A stronger antioxidant effect of the morning compared to evening spiced food was hypothesized considering the gradual increase in plasma malondialdehyde concentrations in the morning [35,37].…”

Circadian Blood Pressure Rhythm in Cardiovascular and Renal Health and Disease

“…The core clock genes can also regulate the coupling of eNOS and contribute to the maintenance of rhythmicity of endothelial function and BP [21]. Similarly, although 3.5-day rhythm and 8-hourly change have been reported in the human circulation [22], the secretion of endothelin 1 (ET-1) in plasma and excretion in urine has been also pronouncedly confirmed to be circadian rhythmic and closely related with BP homeostasis [23][24][25]. ET-1 receptor antagonists had been For instance, melatonin, secreted from the pineal gland at night, may significantly reduce nocturnal BP and improve sleep in patients with essential hypertension [13].…”