Bock, Joshua M.

Excessive daytime sleepiness (EDS) is classically viewed as a consequence of insufficient sleep or a symptom of sleep disorders. Epidemiological and clinical evidence have shown that patients reporting EDS in tandem with sleep disorders (e.g., obstructive sleep apnoea) are at greater cardiovascular risk than non-sleepy patients. While this may simply be attributable to EDS being present in patients with a more severe condition, treatment of sleep disorders does not consistently alleviate EDS, indicating potential aetiological differences. Moreover, not all patients with sleep disorders report EDS, and daytime sleepiness may be present even in the absence of any identifiable sleep disorder; thus, EDS could represent an independent pathophysiology. The purpose of this review is twofold: first, to highlight evidence that EDS increases cardiovascular risk in the presence of sleep disorders such as obstructive sleep apnoea, narcolepsy and idiopathic hypersomnia and second, to propose the notion that EDS may also increase cardiovascular risk in the absence of known sleep disorders, as supported by some epidemiological and observational data. We further highlight preliminary evidence suggesting systemic inflammation, which could be attributable to dysfunction of the gut microbiome and adipose tissue, as well as deleterious epigenetic changes, may promote EDS while also increasing cardiovascular risk; however, these pathways may be reciprocal and/or circumstantial. Additionally, gaps within the literature are noted followed by directions for future research.

Abstract While the contribution of several physiological systems to arterial blood pressure regulation has been studied extensively, the role of normal and disrupted sleep as a modifiable determinant of blood pressure control, and in the pathophysiology of hypertension, has only recently emerged. Several sleep disorders, including sleep apnea and insomnia, are thought to contribute to the development of hypertension, although less attention is paid to the relationship between sleep duration and blood pressure independent of sleep disorders per se. Accordingly, this review focuses principally on the physiology of sleep and the consequences of abnormal sleep duration both experimentally and at the population level. Clinical implications for patients with insomnia who may or may not have abbreviated sleep duration are explored. As a corollary, we further review studies of the effects of sleep extension on blood pressure regulation. We also discuss epidemiological evidence suggesting that long sleep may also be associated with hypertension and describe the parabolic relationship between total sleep time and blood pressure. We conclude by highlighting gaps in the literature regarding the potential role of gut microbial health in the cross-communication of lifestyle patterns (exercise, diet, and sleep) with blood pressure regulation. Additionally, we discuss populations at increased risk of short sleep, and specifically the need to understand mechanisms and therapeutic opportunities in women, pregnancy, the elderly, and in African Americans.

Traditionally regarded as a consequence of sleep‐disordered breathing, excessive daytime sleepiness (EDS) is now recognized as an independent risk factor for cardiovascular disease. Evidence also links the shortening of telomeres, responsible for protecting DNA, with increased cardiovascular disease risk. Interestingly, recent data illustrate telomere lengthening in patients with obstructive sleep apnea (OSA); however, whether EDS is associated with telomere length independently of OSA remains unknown. To examine this potential relationship, we studied 169 subjects with polysomnography assessment who answered “yes” or “no” to experiencing EDS; 70 subjects (41%) reported EDS (59M, 44±12yrs, 30.3±5.5kg/m 2 ) whereas 99 did not (59%, 71M, 40±15yrs, 28.6±7.5kg/m 2 ). Telomere length was quantified via qPCR of genomic DNA isolated from peripheral blood samples and did not differ between individuals reporting EDS compared to those who did not (4,856±280 vs. 4,880±340bp, respectively, P =0.31). However, 50% of subjects reporting EDS had moderate‐to‐severe OSA (apnea‐hypopnea index ≥15events/hr) compared to 28% of the non‐EDS group ( P <0.01). To account for the confounding effects of OSA on telomere length, we conducted a series of subgroup analyses. Subjects without OSA who reported EDS (n=35, 27M, 39±11yrs, 27.4±5.0kg/m 2 ) had shorter telomeres (4,805±165 vs. 4,875±231bp, P =0.05) than those not reporting EDS (n=71, 47M, 35±11yrs, 26.8±5.4kg/m 2 ). Interestingly, within the OSA subgroup, there were no differences in telomere length (4,897±235 vs. 4,858±251bp, P =0.45) between those with (n=35, 32M, 48±11yrs, 33.2±4.5kg/m 2 ) and without EDS (n=28, 24M, 53±16yrs, 33.1±9.7kg/m 2 ). These effects do not appear to be influenced by subject demographics as no differences were found between compared groups (EDS‐OSA vs. nEDS‐OSA and OSA+EDS vs. OSA‐EDS). Collectively, our data suggest individuals reporting EDS may be at greater risk of developing cardiovascular disease due to accelerated telomere shortening. It also appears OSA and EDS exert differential effects on telomere length.

Aging is associated with increased peripheral chemoreceptor activity, reduced nitric oxide (NO) bioavailability, and attenuation of cardiovagal baroreflex sensitivity (BRS), collectively increasing the risk of cardiovascular disease. Evidence suggests that NO may attenuate peripheral chemoreflex sensitivity and increase BRS. Exogenous inorganic nitrate ([Formula: see text]) increases NO bioavailability via the [Formula: see text]-[Formula: see text]-NO pathway. Our hypothesis was that inorganic [Formula: see text] supplementation would attenuate peripheral chemoreflex sensitivity and enhance spontaneous cardiovagal BRS in older adults. We used a randomized, placebo-controlled crossover design in which 13 older (67 ± 3 yr old) adults ingested beetroot powder containing (BRA) or devoid of (BRP) [Formula: see text] and [Formula: see text] daily over 4 wk. Spontaneous cardiovagal BRS was assessed over 15 min of rest and was quantified using the sequence method. Chemoreflex sensitivity was assessed via ~5 min of hypoxia (10% fraction of inspired O2) and reported as the slope of the relationship between O2 saturation (%[Formula: see text]) and minute ventilation (in l/min) or heart rate (in beats/min). Ventilatory responsiveness to hypoxia was reduced after BRA (from −0.14 ± 0.04 to −0.05 ± 0.02 l·min−1·%[Formula: see text]−1, P = 0.01) versus BRP (from −0.10 ± 0.05 to −0.11 ± 0.05 l·min−1·%[Formula: see text]−1, P = 0.80), with no differences in heart rate responsiveness (BRA: from −0.47 ± 0.06 to −0.33 ± 0.04 beats·min−1·%[Formula: see text]−1, BRP: from −0.48 ± 0.07 to −0.42 ± 0.06 beats·min−1·%[Formula: see text]−1) between conditions (interaction effect, P = 0.41). Spontaneous cardiovagal BRS was unchanged after BRA and BRP (interaction effects, P = 0.69, 0.94, and 0.39 for all, up, and down sequences, respectively), despite a reduction in resting systolic and mean arterial blood pressure in the experimental (BRA) group ( P < 0.01 for both). These findings illustrate that inorganic [Formula: see text] supplementation attenuates peripheral chemoreflex sensitivity without concomitant change in spontaneous cardiovagal BRS in older adults. NEW & NOTEWORTHY Exogenous inorganic nitrate supplementation attenuates ventilatory, but not heart rate, responsiveness to abbreviated hypoxic exposure in older adults. Additionally, inorganic nitrate reduces systolic and mean arterial blood pressure without affecting spontaneous cardiovagal baroreflex sensitivity. These findings suggest that inorganic nitrate may attenuate sympathetically oriented pathologies associated with aging.