Three hours of sitting resulted in a significant impairment in shear rate and SFA FMD. When light activity breaks were introduced hourly during sitting, the decline in FMD was prevented.

All species organize behaviors to optimally match daily changes in the environment, leading to pronounced activity/rest cycles that track the light/dark cycle. Endogenous, approximately 24-hour circadian rhythms in the brain, autonomic nervous system, heart, and vasculature prepare the cardiovascular system for optimal function during these anticipated behavioral cycles. Cardiovascular circadian rhythms, however, may be a double-edged sword. The normal amplified responses in the morning may aid the transition from sleep to activity, but such exaggerated responses are potentially perilous in individuals susceptible to adverse cardiovascular events. Indeed, the occurrence of stroke, myocardial infarction, and sudden cardiac death all have daily patterns, striking most frequently in the morning. Furthermore, chronic disruptions of the circadian clock, as with night-shift work, contribute to increased cardiovascular risk. Here we highlight the importance of the circadian system to normal cardiovascular function and to cardiovascular disease, and identify opportunities for optimizing timing of medications in cardiovascular disease.

IntroductionIt is unknown if there are limb differences in vascular function during prolonged sitting.PurposeThis study was designed to test whether the effects of prolonged sitting on brachial artery (BA) and the superficial femoral artery (SFA) are similar.MethodsTwelve men (24.2 ± 4 yrs.) participated in a 3 hr prolonged sitting trial (SIT). SFA and BA flow mediated dilation (FMD) and respective flow patterns were measured at baseline, 1 hr, 2 hr and 3 hr.ResultsBy a one-way ANOVA there was a significant decline in SFA FMD during 3 hrs of SIT (p < 0.001). Simultaneously, there was a significant decline in antegrade (p = 0.04) and mean (0.037) shear rates. By a one way ANOVA there were no significant differences in BA FMD during 3 hrs of sitting. There were no changes in the shear rates in the BA except for a significant decrease in antegrade shear rate (p = 0.029) and a significant increase in oscillatory shear index (p = 0.034) during 3 hrs of sitting. Furthermore, there was no correlation between BA and SFA FMD measurements.ConclusionThree hours of sitting resulted in impaired SFA FMD but not BA FMD. Although 3 hours of sitting did not impair BA FMD, it impaired shear patterns in the BA.

Given the emerging knowledge that circadian rhythmicity exists in every cell and all organ systems, there is increasing interest in the possible benefits of chronotherapy for many diseases. There is a well-documented 24-h pattern of blood pressure with a morning surge that may contribute to the observed morning increase in adverse cardiovascular events. Historically, antihypertensive therapy involves morning doses, usually aimed at reducing daytime blood pressure surges, but an absence of nocturnal dipping blood pressure is also associated with increased cardiovascular risk. To more effectively reduce nocturnal blood pressure and still counteract the morning surge in blood pressure, a number of studies have examined moving one or more antihypertensives from morning to bedtime dosing. More recently, such studies of chronotherapy have studied comorbid populations including obstructive sleep apnea, chronic kidney disease, or diabetes. Here, we summarize major findings from recent research in this area (2013-2017). In general, nighttime administration of antihypertensives improved overall 24-h blood pressure profiles regardless of disease comorbidity. However, inconsistencies between studies suggest a need for more prospective randomized controlled trials with sufficient statistical power. In addition, experimental studies to ascertain mechanisms by which chronotherapy is beneficial could aid drug design and guidelines for timed administration.

SummarySedentary activity is a modifiable life-style behavior and a key component in the etiology of atherosclerotic cardiovascular disease (ACVD). US adults and children spend more than half their waking time in sedentary pursuits. Sedentary activity has been shown to result in impaired insulin sensitivity, impaired metabolic function and attenuated endothelial function, which are classic markers of ACVD. Sedentary activity is defined as ‘sitting without otherwise being active.’ This behavior promotes reduced muscular activity of the lower extremities which decreases leg blood flow, increases blood pooling in the calf, augments mean arterial pressure, and deforms arterial segments resulting in low mean shear stress (SS). SS activates distinct physiological mechanisms which have been proposed to be protective against ACVD; specifically through a SS-induced endothelium-derived nitric oxide mechanism. Reduced bioavailability of nitric oxide creates a pro-oxidant milieu resulting in increased oxidative stress. There is sufficient evidence which demonstrates that endothelial function is attenuated in the presence of oxidative stress. Sedentary activity results in low SS in the lower extremities which may result in increased oxidative stress and impaired endothelial function. This review furthers the use of sitting as model to study the effects of inactivity, discusses possible physiological mechanisms and suggests future directions.

community stakeholders regarding obstructive sleep apnea. (3) Increase the proportion of students in grades 9 through 12 who get sufficient sleep and (4) Perform trials aimed at improving adherence to treatments for sleep-disordered breathing (particularly evaluating cognitive therapy approaches). The fourth priority area was identified as an important barrier to implementation science efforts in sleep.

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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.