Sleep Duration and Hypertension: Epidemiological Evidence and Underlying Mechanisms

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.

Defined as a resting systolic blood pressure over 130 mm Hg, diastolic blood pressure exceeding 80 mm Hg, or use of antihypertensive medication,¹ hypertension is a well-known risk factor for cardiovascular disease and mortality.² The prevalence of hypertension is very high, affecting nearly half of Americans.³ Several organ systems and signaling pathways are involved in the regulation of blood pressure, cohesively summarized as the “Mosaic Theory” by Page some 70 years ago.⁴ Despite a myriad of evidence, sleep duration, independent of sleep pathologies (such as obstructive sleep apnea), receives little discussion as a determinant of blood pressure Furthermore, while observational data suggest that shortened sleep, whether due to acute or chronic disruptions are associated with increased blood pressure and hypertension, respectively,⁵ our understanding of the mechanism(s) responsible for these relationships remain incomplete. This is, in part, due to the challenges associated with isolating disrupted sleep from a cluster of other lifestyle and behavioral factors, such as physical inactivity⁶ and poor dietary choices,⁷ which are each independently associated with both truncated sleep and hypertension. This review discusses the effects of sleep restriction and extension on blood pressure regulation, along with common clinical manifestations, as well as mechanistic evidence from recent experiments in preclinical and translational models to serve as a resource for future studies.

NORMAL SLEEP

Before understanding how altered sleep facilitates the onset of hypertension, it is important to first review a “normal” night’s sleep. Principally, total sleep time is used to provide recommendations to the public⁸ and while individual sleep demands can vary greatly between genetically similar humans,⁹ both the American Academy of Sleep Medicine and Sleep Research Society suggest most adults receive between 7 and 9 hours per night.⁸ Despite this generic but reasonable guide, it is important to note that each sleep stage has a unique duration, physiology, and pattern of blood pressure. Briefly, the least amount of total sleep time is spent in stage 1 (N1) sleep in contrast to stage 2 (N2) which is the longest irrespective of age.¹⁰ Time spent in stage 3, or slow-wave sleep, declines as we age largely due to increased wakefulness after sleep onset.¹⁰ Collectively, these first 3 stages of sleep are referred to as nonrapid eye movement sleep and are characterized by a progressive decline in blood pressure, heart rate, cardiac output, and sympathetic nerve activity¹¹ to ultimately manifest as the classic nocturnal “dipping” pattern.¹² Hallmarks of rapid eye movement include blood pressure and heart rate levels similar to waking values accompanied by marked elevations in sympathetic nerve traffic.¹¹ Throughout the night, the distribution of time spent in a given stage varies as evidenced by rapid eye movement occurring predominantly during the second half of sleep.¹³

SLEEP RESTRICTION

Approximately 1-in-3 Americans reports achieving less than 7 hours of sleep per night with patterns of short sleep clustering in geographic regions with the highest prevalence of cardiometabolic disease.¹⁴ Indeed, Kripke et al.¹⁵ found sleeping less than 7 hours per night was associated with a 15% rise in mortality after adjusting for age, preexisting health conditions, and prescription medication use. It is important to note these data were collected during the 1980s and, since then, average subjective sleep duration has declined evidenced by a 30% rise in adults sleeping less than 6 hours per night.¹⁶ Further, sleeping fewer than 5 hours each night is associated with a more than 2-fold elevation in the risk of developing hypertension.¹⁷ Along these lines, Yang et al.¹⁸ found a 10% increase in cardiovascular and all-cause mortality for each hour less of sleep. Clearly, reductions in sleep duration are associated with increases in blood pressure¹⁹ which has prompted mechanistic studies seeking to elucidate the underlying mechanism(s).

Metabolism

Subjects exposed to experimental sleep restriction tend to consume more calories which may precipitate obesity-related hypertension. Specifically, data from our laboratory report a 500 kcal per day increase in total caloric consumption following 1.5 fewer hours of sleep over 8 days,²⁰ suggesting weight gain may contribute to blood pressure elevation following truncated sleep over time. Cross-sectional data indicate short sleep duration (6–8 hours per night) is associated with elevated risk for impaired fasting glucose (6%), central obesity (12%), and hypertension (8%).²¹ Similar findings have been reported in adolescents whereby sleeping less than 8 hours per night is associated with reduced insulin sensitivity relative to those sleeping more than 8 hours as determined via gold-standard hyperglycemic clamp studies.²² Interestingly, Robertson et al.²³ found 8 weeks of sleep restriction (1.5 hours less per night) did not increase body mass; rather, fasting glucose was higher coinciding with reduced insulin sensitivity which correlated to greater fat mass (r = −0.29). More acutely, blood glucose and insulin were raised following 4 nights of sleep restriction (4 hours of sleep per night) although measures of insulin sensitivity were unchanged.²⁴ Additionally, cortisol was also elevated without commensurate changes observed in adrenocorticotropic hormone suggesting alterations in adrenal function may have occurred. Spiegel et al.,²⁵ using the same protocol (6 days of 4 hours sleep each night), found the unfavorable changes in blood glucose were associated with increased sympathetic nerve activity. Collectively, these data suggest that restriction of sleep is associated with greater caloric intake as well as blood glucose and insulin levels which appear to alter sympathovagal balance; however, variable interstudy dietary regulations (e.g., ad libitum vs. semicontrolled) make mechanistic conclusions challenging.

The autonomic nervous system

Composed of sympathetic and parasympathetic (vagal) branches, the autonomic nervous system regulates blood pressure homeostasis through a series of reflexes, principally, the baroreflex.²⁶ Here, increased blood pressure is sensed by stretch receptors of the carotid sinus and aortic arch which, via afferent signaling to the rostral ventrolateral medulla, suppress sympathetic outflow.²⁷ A study from the Carter laboratory reported 24 hours of sleep deprivation increased blood pressure but reduced sympathetic tone in young healthy men with no changes in women.²⁸ In succeeding experiments, the effects of aging on the same 24 hours of sleep deprivation were investigated in 10 older men and 10 older women (aged 55–75 years) and findings showed that systolic blood pressure increased in both men (Δ6 mm Hg) and women (Δ9 mm Hg), although, sympathetic nerve traffic was exclusively elevated in women.²⁹ Heart rate variability is a noninvasive alternative to estimating sympathovagal balance.³⁰ Using this approach, Tobaldini et al.³¹ studied on-call resident physicians following 1 night of sleep deprivation, finding attenuated high-frequency variability (suggestive of parasympathetic activity) with concomitant rise in low-frequency variability (suggestive of sympathetic activity) and a blunted orthostatic response to head-up tilt. These findings appeared to persist up to 40 hours³² of sleep deprivation indicating baroreflex dysfunction may contribute to elevations in blood pressure. Collectively, experimental sleep restriction and deprivation increase sympathetic outflow in nearly all studies which some,³³ but not all,³⁴ have correlated to increased blood pressure. While the mechanism(s) responsible for these differential effects remain to be elucidated, evidence from animal and human studies describe a role for inflammation.

Inflammation

The link between inflammation and hypertension has been studied for over 50 years as first described by Olsen.³⁵ More recent evidence from preclinical experiments demonstrate chronic sleep restriction activates transcriptional pathways of inflammation (e.g., nuclear factor kappa B) in the hippocampus which phenotypically translated to cognitive impairment and patterns of anxiety.³⁶ Complementary studies from Kincheski et al.³⁷ reported neuroinflammation following chronic sleep restriction along with a potentiated response to amyloid-β oligomers (suggesting a predisposition to developing Alzheimer’s disease) which was abolished with pretreatment of infliximab, a TNFα inhibitor. Beyond the effects of cytokines on the autonomic nervous system, inflammation also significantly impairs vascular health. Work from Ross³⁸ in the 1980s reported inflammation-induced macrophage infiltration of vascular smooth muscle cells as a fundamental pathophysiological process of atherosclerotic cardiovascular disease. Over 15 years later, the diurnal pattern of inflammatory cytokine secretion was identified in humans during the 1990s with a linear relationship between total sleep time and interleukin-6 concentrations.³⁹ The authors also noted basal slow-wave sleep was associated with the change in interleukin-6 levels after 1 night of sleep restriction. Succeeding studies report these findings persist with time as 5 nights of sleep restriction not only increased cytokines, but levels continued to increase during the recovery period.⁴⁰ In a robust study from Meier-Ewert et al.⁴¹ both sleep deprivation (88 hours of continuous wakefulness) and restriction (4.2 hours of sleep per night for 10 days) increased high-sensitivity C-reactive protein as well as systolic blood pressure and heart rate, respectively. Epidemiological data from Ferrie et al.⁴² built upon this work by reporting each hour of sleep lost was associated with an 8.1% increase in C-reactive protein and 4.5% increase of interleukin-6 levels. Complementary immunohistochemical imaging also identified relationships between sleep quality and nuclear factor kappa B activation within endothelial cells. As reviewed by McMaster et al.,⁴³ inflammatory cytokines, which accumulate in both peripheral and renal vascular beds, increase blood pressure through a myriad of mechanisms including endothelial dysfunction.

Endothelial dysfunction

A wealth of evidence supports the role of endothelial dysfunction, or attenuated endothelium-dependent nitric oxide (NO) production, in the etiology of hypertension.⁴⁴ Regarding sleep, 40 hours of consecutive wakefulness,³² and 6 days of 4 hours of sleep per night,⁴⁵ impairs cutaneous microvascular endothelial function in healthy young adults, which appeared to precede elevations in blood pressure. Similarly, brachial artery flow-mediated dilation, considered the gold-standard technique to assess endothelial function noninvasively,⁴⁶ was reduced by 50% in healthy college students following 4 weeks of 20% sleep restriction with a 3 mm Hg commensurate rise in systolic blood pressure.⁴⁷ Our previous work reported 8 days of sleep restriction (1.5 hour per night reduction of total sleep time), in healthy young adults, led to a robust decline in conduit artery flow-mediated dilation (8.4%–5.2%) accompanied by a 2 mm Hg rise in systolic blood pressure.²⁰ For clinical reference, a 1% reduction in flow-mediated dilation increases cardiovascular risk by 13% in patients with known pathologies and a 4% increase in risk for healthy adults⁴⁸ while a 2 mm Hg increase in systolic blood pressure corresponds to a 7% increase in cardiovascular mortality.² More recently, we demonstrated 9 days of sleep restriction (4 hours of sleep per night) led to a decline in endothelial function which was associated with a commensurate rise in waking, sleeping, and 24-hour systolic blood pressure in healthy young women.⁴⁹ A multitude of factors and signaling pathways, both intrinsic and extrinsic to the endothelium, likely co-contributed to this although a likely role for oxidative stress has been identified. Jówko et al.⁵⁰ studied 23 healthy young males who were sleep deprived for 36 hours during a survival training course. The authors noted a robust increase in lipid peroxidation after 24 hours which remained elevated at the 36-hour time point. These findings were accompanied by reciprocal elevation of total antioxidant capacity in plasma and superoxide dismutase activity. Indeed, several studies using murine models show reduced sleep duration leads to oxidative stress⁵¹ via increased NADPH oxidase expression⁵² and reduced antioxidant enzyme activity.⁵³ Mechanistically, reactive oxygen species (e.g., superoxide) bind to NO before it diffuses into the smooth muscle producing peroxynitrite through a process termed “NO scavenging.” This effectively attenuates the vasodilatory effects of NO and manifests as endothelial dysfunction and ultimately, hypertension. Despite this convincing evidence implicating oxidative stress-induced endothelial dysfunction as a cause of hypertension following sleep restriction, deleterious alterations in circadian rhythmicity are known to also play a role.

Clock genes

While hypertension is commonly diagnosed using measurements obtained at rest and during waking hours, assessing day–night changes in blood pressure provides greater predictive power of cardiovascular events and mortality.⁵⁴ Physiologically, the suprachiasmatic nucleus is considered to be the body’s “master clock” whereby surgical lesioning disrupted circadian patterns of systemic hemodynamics.⁵⁵ Similarly, postmortem findings indicate dysregulation of the suprachiasmatic nucleus in deceased patients with hypertension.⁵⁶ Our knowledge on the consequences of circadian disruption stems largely from observational studies in shift workers, with more recent advances involving the field of epigenetics. That is, circadian clock genes have been rigorously studied as mediators of several physiological processes including blood pressure. Much of this literature comes from experiments conducted using preclinical models, as investigating clock genes is particularly challenging in humans due to the required regulation of light exposure, physical activity, and diet.⁵⁷ Functioning through serial transcription and translation, genes such as Bmal1, Clock, Period, and Cryptochrome play a role in circadian blood pressure management. Indeed, multiple linear regression models revealed these collectively predicted systolic blood pressure after adjusting for age, sex, body mass index, prevalence of comorbidities (e.g., type 2 diabetes mellitus, hyperlipidemia), and lifestyle choices (e.g., smoking, physical activity).⁵⁸ Within the context of hypertension, loss of Cryptochrome is associated with a hypertensive phenotype,⁵⁹ whereas upregulation of the others may also increase blood pressure.^60–62 As clock genes are expressed ubiquitously, the mechanism(s) linking circadian disruption to hypertension are multifaceted and include many of those discussed in the aforementioned sections. For instance, mice deficient in Bmal1 had greater Clock activation which was associated with oxidative stress and endothelial cell inflammation via nuclear factor kappa B activation.⁶³ Furthermore, the mechanism(s) which drive clock gene disruption are incompletely understood, although recent data suggest cellular senescence⁶⁴ and telomere shortening⁶⁵ may play a role.

Insomnia

Insomnia affects up to 50% of the general population at any point in time⁶⁶ and approximately 10%–20% of adults chronically.⁶⁷ Individuals with insomnia frequently report difficulty getting to sleep or staying asleep and are at 23% greater risk of cardiovascular mortality⁶⁸ largely attributable to the 50% increase in risk of developing hypertension.⁶⁹ For patients with insomnia, those with objectively short sleep duration are particularly susceptible to developing cardiovascular disease possibly due to being in a state of hyperarousal indicated by elevated hypothalamic–pituitary–adrenal axis (e.g., cortisol) and sympathetic activity (e.g., norepinephrine).⁷⁰ Moreover, patients with insomnia have reduced baroreflex sensitivity along with exaggerated blood pressure responses to sympathoexcitation indicating greater risk for future development of hypertension and cardiovascular disease.⁷¹ Contributing to the increased risk of hypertension and cardiovascular mortality in patients with insomnia is a heightened inflammatory state possibly associated with dysbiosis of the gut microbiome.⁷² As outlined in a recent review by Avery et al.,⁷³ bacterial disturbances within the gastrointestinal tract can prompt a systemic inflammatory response, largely mediated by the immune system, which manifests as hypertension. In a recent open-label trial, supplementation of the probiotic Lactobacillus plantarum over 8 weeks was associated with lower levels of cortisol as well as improved subjective indices of sleep and stress.⁷⁴ Although blood pressure was unaffected, subjects in this study were considered normotensive indicating the potential of a therapeutic ceiling.

Summary—sleep restriction

Chronic short sleep is increasingly common across the United States and is associated with the development of hypertension. Studies using experimental sleep curtailment have suggested deleterious changes in metabolism, sympathovagal imbalance, and endothelial dysfunction contribute to the hypertensive phenotype with reduced sleep. Molecular mechanisms for these findings center on inflammatory cytokines and oxidative stress which share a complex relationship with circadian clock gene expression. Circadian misalignment can also facilitate increases in blood pressure although translational studies in humans are sparse. Clinically, patients with insomnia reporting short sleep frequently present with hypertension attributable in part to a heightened sympathetic and inflammatory state. Emerging evidence indicates dysbiosis of the gut microbiome may contribute to these observations and is the target of recent interventional studies. Simply summarized, a large body of evidence is supportive of the concept that insufficient sleep increases blood pressure with consequent elevation in risk of cardiovascular events.

SLEEP EXTENSION

With ample evidence on the deleterious effects of reduced sleep duration, it is tempting to speculate that sleep extension would reduce blood pressure, and subsequently cardiovascular risk, particularly in chronic short sleepers. Surprisingly, there are far fewer studies examining the role of sleep extension, in contrast to sleep restriction or deprivation, as a therapeutic approach to treat hypertension. This concept was first tested in shift workers who characteristically have insufficient sleep during weekdays. Here, increasing time in bed by 1–2 hours per night over 3 consecutive weekends did not reduce either systolic or diastolic blood pressure.⁷⁵ While at surface level these data are unexpected, it is important to differentiate time in bed from the duration of sleep. To this point, population-scale data from South Korea found increasing self-reported sleep duration by 1 hour during weekends reduced the risk of developing hypertension by 17% across their entire cohort and 39% within subjects experiencing sleep insufficiency.⁷⁶ Similar data were found in a smaller (n = 13) prospective study of patients with prehypertension who slept less than 7 hours per night. During this trial, increasing sleep duration by approximately 35 minutes per night over 6 weeks decreased systolic and diastolic blood pressure by 14 and 8 mm Hg, respectively.⁷⁷ Interestingly, these results were not paralleled by reductions in inflammatory markers, urine catecholamines, or caloric intake although this may have been due to insufficient statistical power. More recently, Stock et al.⁷⁸ studied the effects of sleep extension over 1 week in healthy college-aged individuals. While only increasing nightly sleep time by 15 minutes, systolic blood pressure was reduced 7 mm Hg which was accompanied by fewer reports of excessive daytime sleepiness. Along with these promising studies, a multitude of recent evidence indicates sleep extension also exerts beneficial effects on cardiometabolic health,^79,80 particularly in those regularly experiencing sleep restriction.⁸¹

Prolonged sleep

Despite the excitement surrounding these data, it is important to note that long sleep times have also been linked to poor outcomes. A meta-regression from Jike et al.⁸² examined the relationships between long sleep duration and various cardiometabolic diseases in over 5 million subjects. Their data revealed increased risk of all-cause mortality (39%), type 2 diabetes mellitus (26%), coronary heart disease (24%), and stroke (46%); however, the risk of hypertension was not elevated (RR = 1.01). It is important to note the definition of “long sleep duration” varied between studies included within these analyses ranging from more than 7 hours up to those exceeding 11 hours of sleep per night. Findings from the Sleep Heart Health Study provide intriguing evidence whereby individuals sleeping between 8 and 9 hours per night have similar risk of developing hypertension as those sleeping between 6 and 7 hours (19% increase in risk for both circumstances).⁸³ Furthermore, individuals sleeping more than 9 hours per night have 30% greater risk of hypertension relative to those sleeping between 7 and 8 hours; thus, there appears to be a parabolic relationship between sleep and blood pressure. This notion is supported by a study of aggregate data by Grandner et al.⁸⁴ who reported a U-shaped curve between sleep duration and risk of hypertension after adjusting for confounding factors such as age, body mass index, and alcohol use.

Taken together, preliminary evidence suggests individuals with chronic insufficient sleep demonstrate cardiovascular benefits following sleep extension; principally, reductions in blood pressure. From a therapeutic perspective, sleep extension could therefore be a cost-effective approach to mitigating hypertensive risk particularly in shift workers. Due to the paucity of mechanistic studies in sleep extension, the driving factor(s) responsible for these findings remain to be elucidated. It should be noted that there may be adverse accompaniments of long sleep duration as suggested by epidemiological studies. However, any causal interaction between long sleep and poor outcomes has not been established.

FUTURE DIRECTIONS

In tandem with adequate sleep, exercising regularly and consuming a nutrient-rich diet are critical components to maintaining systemic health. Interestingly, these “pillars” of health appear to cross-communicate whereby the deleterious effects of poor dietary choices on vascular function can be offset by engaging in a de novo exercise regimen.⁸⁵ Building upon this concept, the potential for exercise, or healthy diet, to offset blood pressure elevations induced by sleep restriction remains understudied; for instance, are endurance athletes resistant to the hypertensive phenotype of reduced sleep duration? One potential, novel mediator between exercise, diet, and sleep is the gut microbiome. Indeed, aerobic exercise training,⁸⁶ higher cardiorespiratory fitness,⁸⁷ and adherence to an overall healthy diet⁸⁸ are associated with greater gut microbial health whereby sleep restriction⁸⁹ and sleep quality⁹⁰ are associated with dysbiosis of the microbiome. Therefore, the role of gut microbes in mediating a theorized mitigation of short sleep-induced pressor responses via healthy exercise and dietary patterns should be explored (Table 1).

Table 1.

Summary of future directions

Paradigm	Reference	Findings
Healthy lifestyle choices offset pressor effects of poor sleep via the gut microbiome	Allen et al.86	Six weeks of incremental aerobic exercise training improved β-diversity and fecal SFCA-producing bacteria in lean, but not obese, subjects. These beneficial effects were reversed following a sedentary washout period.
	Durk et al.87	Firmicutes to Bacteroidetes ratio was associated with VO2max in young healthy adults.
	Benedict et al.89	Two days of partial sleep deprivation (~4.25 h/night) increased the Firmicutes to Bacteroidetes ratio and slight phylum-specific changes in diversity.
	Grosicki et al.90	Self-reported sleep quality (PSQI score) was inversely related to α-diversity and the Firmicutes to Bacteroidetes ratio.
Age-related increases in blood pressure	Ohayon et al.10	10 min/night/y less TST, 2% less SWS/decade, curvilinear increase in WASO. Women demonstrated more pronounced attenuation of TST and SWS than men and greater increases in WASO (all modest effect sizes).
	Javaheri et al.91	In middle-aged adults (59 ± 10 y, 55% female), reduced SWS associated with onset of HTN within 5.3 y.
	Virani et al.92	Linear increase in the prevalence of HTN throughout age; more dramatic in women than men. Approximately half of Americans ages 45–54 y have HTN.
Sexual dimorphisms in risk of HTN	Ji et al.93	Systolic blood pressure dramatically increases in women starting at age 45–50 y exceeding males at age 65 y after adjustment for risk factors, antihypertensive therapy, and baseline blood pressure.
	Okada et al.94	Primipara women reporting poor sleep quality (PSQI ≥6) had more dramatic increases in morning systolic blood pressure vs. those reporting good sleep quality.
	Harskamp-van Ginkel et al.95	Self-reported gestational sleep ≤6 h/night associated with increased body mass index, waist circumference, and diastolic blood pressure in their children through 11 y of age being more pronounced in female children.
Racial differences in the prevalence of HTN	Lackland96	Black men and women have consistently higher prevalence of HTN, and lower rates of controlled HTN, compared with white men and women, respectively, since the 1980s.
	Chen et al.97	Independent of age, sex, and obesity status (normal weight, overweight, obese), blacks report shorter sleep duration, worse sleep quality, and greater daytime sleepiness compared with whites.
	Virani et al.92	Blacks residing in the United States, particularly those who are native citizens, have among the highest rates of HTN in the world (58% for men and 53% for women).

Abbreviations: HTN, hypertension; PSQI, Pittsburgh sleep quality index; SFCA, short chain fatty acid; SWS, slow-wave sleep; TST, total sleep time; VO_2max, maximal volume of oxygen consumption; WASO, wake after sleep onset.

The effects of short sleep on blood pressure may be especially relevant to the elderly, women, pregnant, and African Americans. For instance, as humans age, sleep duration is curtailed¹⁰ which parallels an increase in the risk of hypertension.⁹² Whether sleep extension could be leveraged to offset age-related increases in arterial blood pressure remains to be determined. It is also important to note the aging process is fundamentally different between males and females as evidenced by women having disproportionately greater risk of developing hypertension as they age relative to men.⁹³ As observed earlier, recent experimental data show strikingly higher pressor effects of restricted sleep in healthy young females compared with males.⁴⁹ To this point, how sex influences the sleep–blood pressure relationship remains to be examined, particularly in the context of aging. Similarly, sleep duration throughout pregnancy has recently gained attention as poor sleep during the first trimester appears to elevate blood pressure during the third trimester.⁹⁴ Moreover, sleep disturbances, and associated increases in blood pressure, translate to the fetus whereby the children of women reporting sleep disturbances throughout pregnancy also have increased blood pressure and adiposity.⁹⁵ There are also distinct differences in the prevalence of hypertension⁹⁶ as well as in likelihood of short sleep, poor sleep quality, and excessive daytime sleepiness across ethnicities.⁹⁷ Indeed, we have previously highlighted the greater risk of hypertension induced by short sleep duration in African Americans.⁹⁸ Several factors, including those described above (e.g., inflammation, sympathetic nerve activity), contribute to these observations although it remains unknown if enhancing sleep in African Americans is associated with a reduction in blood pressure and cardiovascular risk.

SUMMARY

Hypertension dramatically increases cardiovascular risk with commensurate elevation in mortality. The mechanisms responsible for blood pressure homeostasis are complex and, in many circumstances, redundant. Over the past few decades, sleep has emerged as an integrative regulator of blood pressure whereby both shortened and prolonged sleep duration are associated with the development of hypertension. While several novel prospective and retrospective studies have attempted to elucidate the pathways responsible for these relationships, our knowledge remains incomplete. Nevertheless, available evidence supports a role for deleterious changes in metabolism, autonomic nervous system activity, systemic inflammation, vascular health, and circadian disruption. In addition, parallels between short sleep and hypertension can be drawn in several populations (e.g., elderly, pregnant women, and African Americans); thus, leveraging strategies to improve and enhance sleep, particularly within these individuals, may have significant benefit for their cardiovascular health.

FUNDING

J.M.B. is funded by the National Institutes of Health grant T32-HL007111. S.V. is supported by funding from Sleep Number Corporation to Mayo Clinic. N.C. is supported by the National Institutes of Health grants HL134885 and HL134808, Mayo Clinic Marie Ingalls Research Career Development Award and a grant from Sleep Number Corporation to Mayo Clinic. V.K.S. is funded by grants HL134885 and HL065176 from the National Institutes of Health as well as a grant from Sleep Number Corporation to Mayo Clinic.

DISCLOSURE

J.M.B., S.V., and N.C. have no relevant conflicts of interest to declare. V.K.S. has consulted for Baker Tilly, Respicardia, Jazz Pharmaceuticals, Bayer, and is on the Scientific Advisory Board for Sleep Number Corporation.