Short sleep duration is associated with enhanced endothelin-1 vasoconstrictor toneThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.

Short sleep duration is associated with increased cardiovascular disease (CVD) morbidity. Endothelial vasomotor dysfunction represents a potential mechanism contributing to the increased CVD risk associated with habitual short sleep duration. Endothelin (ET)-1 is a potent vasoconstrictor peptide that is associated with endothelial vasomotor dysfunction and increased CVD risk. Currently, there is no information regarding the influence of short sleep duration on ET-1 vasoconstrictor activity in adults. We tested the hypothesis that ET-1-mediated vasoconstrictor activity is greater in adults who sleep less than 7 h/night (short sleep duration) compared with those who sleep 7–9 h/night (normal sleep duration). Forearm blood flow (FBF) responses to intra-arterial infusion of BQ-123 (100 nmol/min for 60 min), a selective ETAreceptor antagonist, were determined in 80 adults: 50 with normal sleep duration (32 males and 18 females; age: 56.6 ± 1.2 years; sleep: 7.6 ± 0.1 h/night) and 30 with short sleep duration (17 males and 13 females; age: 56.5 ± 1.2 years; sleep: 6.1 ± 0.1 h/night). In response to BQ-123, adults reporting short sleep duration had a greater increase in resting FBF compared with adults reporting normal sleep duration (~20% vs. ~8%; P < 0.05). There was an inverse relation between mean nightly sleep duration and the FBF response to BQ-123 at 60 min (r = –0.29, P < 0.05). These findings indicate that habitual short sleep duration is associated with greater ET-1-mediated vasoconstrictor tone. Increased ET-1 vasoconstrictor activity may contribute to the elevated CVD risk associated with chronic reductions in sleep duration.

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Abstract 2455: Short Sleep Duration is an Independent Predictor of Cardiovascular Events in Hypertensive Patients

Circulation ◽

10.1161/circ.118.suppl_18.s_728-c ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Kazuo Eguchi ◽

Thomas G Pickering ◽

Joseph E Schwartz ◽

Satoshi Hoshide ◽

Joji Ishikawa ◽

...

Keyword(s):

Sleep Duration ◽

Short Duration ◽

Cardiovascular Events ◽

Sleep Time ◽

Cvd Risk ◽

Short Sleep Duration ◽

Hypertensive Patients ◽

Short Sleep ◽

Multivariable Analyses ◽

Normal Sleep

We aimed this study to test the hypothesis that short duration of sleep is independently associated with incident cardiovascular diseases (CVD) in hypertensive patients. We performed ambulatory BP monitoring (ABPM) in 1255 subjects with hypertension (mean age: 70.4 ± 9.9 years) and they were followed for an average of 50 ± 23 months. Short sleep duration was defined as <7.5 hrs (20 th percentile). Multivariable Cox hazard models predicting CVD events were used to estimate the adjusted hazard ratio (HR) and 95% CI for short sleep duration. A riser pattern was defined when average nighttime SBP exceeded daytime SBP. The end point was cardiovascular events: stroke, fatal or non-fatal myocardial infarction (MI), and sudden cardiac death. In multivariable analyses, short duration of sleep (<7.5 hrs) was associated with incident CVD (HR=1.68; 1.06 –2.66, P=.03). A synergistic interaction was observed between short sleep duration and the riser pattern (P=.089). When subjects were categorized on the basis of their sleep time and riser/non-riser patterns, the shorter sleep+riser group had a highest incidence of CVD among the 4 groups ( Figure ), and substantially and significantly higher incidence of CVD than the predominant normal sleep+non-riser group (HR=4.43; 2.09 –9.39, P<0.001), independent of covariates. Short duration of sleep is associated with incident CVD risk, and the combination of riser pattern and short duration of sleep that is most strongly predictive of future CVD, independent of ambulatory BP levels. Physicians should inquire about sleep duration in the risk assessment of hypertensive patients.

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Abstract P545: Insufficient Sleep and Nitric Oxide-Mediated Endothelium-Dependent Vasodilation in Adults With Elevated Blood Pressure

Circulation ◽

10.1161/circ.141.suppl_1.p545 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Kelly A Stockelman ◽

Anthony R Bain ◽

Dana M Withrow ◽

Tracey A Larson ◽

Elizabeth M Boland ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Blood Pressure ◽

Sleep Duration ◽

Elevated Blood Pressure ◽

Elevated Blood ◽

Short Sleep Duration ◽

Insufficient Sleep ◽

Short Sleep ◽

Normal Sleep

Elevated blood pressure (BP ≥130/80 mmHg) is associated with increased risk for myocardial infarction, heart failure, stroke and vascular disease. Insufficient nightly sleep (<7 h/night) has been linked not only to the etiology of elevated blood pressure but is a prevalent, often ignored, comorbidity. Indeed, short sleep duration is now considered to be a plausible risk factor for elevated blood pressure and a harbinger of increased cardiovascular risk. A high prevalence of insufficient nightly sleep has been reported in adults with elevated blood pressure. The influence of insufficient sleep on endothelial vasodilator function in adults with elevated blood pressure is unknown. We tested the hypotheses that chronic insufficient sleep is associated with diminished nitric oxide (NO)-mediated endothelium-dependent vasodilation in adults with elevated blood pressure. Moreover, the insufficient sleep-related reduction in endothelial vasodilator function is due, at least in part to increased oxidative stress. Thirty-five middle-aged and older adults with elevated blood pressure were studied: 15 with normal nightly sleep duration (11M/4F; age: 58±2 yr; BP: 136/82±1/2 mmHg; sleep: 7.6±0.2 h/night) and 20 with short nightly sleep duration (14M/6F; 58±1 yr; BP: 138/84±1/1 mmHg; sleep: 6.0±0.1 h/night). Forearm blood flow (FBF) responses to intra-arterial infusion of acetylcholine (ACh), in the absence and presence of the endothelial NO synthase inhibitor N G -monomethyl-L-arginine (L-NMMA) and the antioxidant vitamin C were determined by venous occlusion plethysmography. The FBF response to ACh was significantly lower (~20%) in the short sleep (from 3.8±0.2 to 11.0±0.6 ml/100 ml tissue/min) compared with the normal sleep duration group (from 4.2±0.2 to 13.6±0.6 ml/100 ml tissue/min). L-NMMA significantly reduced (~25%) the FBF response to ACh in the normal sleep but not the short sleep group. Vitamin C markedly increased (~35%; P<0.05) the vasodilator response to ACh in short sleepers only. In summary, habitual short sleep duration worsens NO-mediated endothelium-dependent vasodilation in adults with elevated blood pressure. Furthermore, the sleep-related diminishment in endothelial vasodilator function is due, in part, to increased oxidative stress.

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Contribution of short sleep duration to ethnic differences in cardiovascular disease: results from a cohort study in the Netherlands

BMJ Open ◽

10.1136/bmjopen-2017-017645 ◽

2017 ◽

Vol 7 (11) ◽

pp. e017645 ◽

Cited By ~ 5

Author(s):

Kenneth Anujuo ◽

Charles Agyemang ◽

Marieke B Snijder ◽

Girardin Jean-Louis ◽

Bert-Jan van den Born ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

The Netherlands ◽

Sleep Duration ◽

Ethnic Differences ◽

Urban Setting ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Short Sleep Duration ◽

Short Sleep

ObjectivesWe analysed association between short sleep duration and prevalence of cardiovascular disease (CVD) in a multiethnic population living in the Netherlands, and the contribution of short sleep to the observed ethnic differences in the prevalence of CVD, independent of CVD risk factors.Methods20 730 participants (aged 18–71 years) of the HELIUS (Healthy Life in an Urban Setting) Study were investigated. Self-reported sleep duration was classified as: short (<7 hours/night) and healthy (7–9 hours/night). Prevalence of CVD was assessed using the Rose Questionnaire on angina pectoris, intermittent claudication and possible myocardial infarction. Association of short sleep duration with prevalent CVD and the contribution of short sleep to the observed ethnic differences in the prevalence of CVD were analysed using adjusted prevalence ratio(s) (PRs) with 95% CI.ResultsResults indicate that short sleep was associated with CVD among all ethnic groups with PRs ranging from 1.41 (95% CI 1.21 to 1.65) in Moroccans to 1.62 (95% CI 1.20 to 2.18) in Dutch after adjustment for age, sex and conventional CVD risk factors. The independent contributions of short sleep (in percentage) to ethnic differences in CVD compared with Dutch were 10%, 15%, 15%, 5% and 5% in South-Asian Surinamese, African-Surinamese, Ghanaian, Turkish and Moroccan, respectively.ConclusionShort sleep contributed to ethnic differences in CVD independent of well-known CVD risk factors particularly in Surinamese and Ghanaian groups. Reducing sleep deprivation may be a relevant entry point for reducing increased CVD risks among the various ethnic minority groups.

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Insomnia and sleep state misperception: Clinical features, diagnosis, management and implications

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.1696 ◽

2017 ◽

Vol 41 (S1) ◽

pp. s853-s853

Author(s):

J. Isaac ◽

C. Santos ◽

A. Matos Pires

Keyword(s):

Sleep Duration ◽

Clinical Features ◽

Mental Disease ◽

Sleep Time ◽

Sleep State ◽

Short Sleep Duration ◽

Short Sleep ◽

Psychological Therapies ◽

Normal Sleep ◽

Competing Interest

BackgroundInsomnia is a highly prevalent complaint, largely associated with mental disease. Clinical evidence classifies insomnia in 2 subtypes: with sleep misperception (WSM) and without sleep misperception (wSM). That presents distinctive pathophysiologic pathways and different public health implications.ObjectivesDescribe the main differences between primary insomnia WSM and wSM regarding:– clinical features;– diagnosis;– management;– implications.MethodsWe conducted a systematic review. PubMed, Embase and PsycInfo were searched from 2000–2016. The reference lists of systematic reviews, narrative synthesis and some important articles were included. Following the inclusion criteria, we selected 25 studies from 59 articles.ResultsThe prevalence of sleep-state misperception in primary insomniacs (total sleep time > 6.5 h and sleep efficiency > 85%) is around 26%. Insomniacs with normal sleep duration showed a profile of high depression and anxiety and low ego strength, whereas insomniacs with short sleep duration showed a profile of a medical disorder.Cortical hyperarousal is higher in insomniacs and could be related to an alteration in sleep protection mechanisms. The sleep architecture was relatively normal for the WSM comparing with the group wSM. Risk of cardiometabolic, neurocognitive morbidity and mortality, and responses to treatment are different between these two insomnia phenotypes. Patients with short sleep duration may respond better to biological treatments, whereas insomnia with normal sleep duration may respond primarily to psychological therapies.ConclusionsThe clinical characteristics of patients with sleep-state misperception differed from those without this condition. Available research related to these conditions is expanding rapidly, but many questions remain unanswered.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Abstract P183: Influence of Insufficient Sleep on Endothelial Fibrinolytic Capacity in Adults With Elevated Blood Pressure

Hypertension ◽

10.1161/hyp.70.suppl_1.p183 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Anthony R Bain ◽

Caitlin A Dow ◽

Kyle J Diehl ◽

Tyler D Bammert ◽

Jared J Greiner ◽

...

Keyword(s):

Sleep Duration ◽

Tissue Type ◽

Short Sleep Duration ◽

Insufficient Sleep ◽

Short Sleep ◽

Type Plasminogen Activator ◽

Increased Risk ◽

Normal Sleep ◽

Middle Aged Adults

The capacity of the endothelium to release tissue-type plasminogen activator (t-PA) is impaired in adults with elevated BP, leading to an increased risk of thrombotic events. Insufficient sleep is independently associated with elevated BP and impaired t-PA release. However, the compounded influence of insufficient sleep on t-PA release in adults with elevated BP is unknown. We tested the hypothesis that impairments in the capacity of the endothelium to release t-PA in adults with elevated BP is worse in those who sleep <7 h/night (short sleep duration) compared with those who sleep 7 to 9 h/night (normal sleep duration). We studied 38 sedentary, middle-aged adults: 10 with normal BP and normal nightly sleep duration (6M/4F; age: 55±2 yr; BP: 114/94±2/3 mmHg, sleep duration: 7.4±0.2 h); 14 with elevated BP and normal nightly sleep duration (8M/6F; 60±2 yr; 141/87±2/2 mmHg; 7.8±0.1 h); and 14 with elevated BP and short nightly sleep duration (10M/4F; 57±2 yr; 139/85±2/2 mmHg; 6.1±0.2 h). All subjects were free of overt metabolic and coronary disease. Net endothelial release of t-PA was determined, in vivo, in response to intra-brachial infusions of bradykinin (BK: 125-500 ng/min) and sodium nitroprusside (SNP: 2.0-8.0 μg/min). In the normal sleep groups, as expected, endothelial t-PA release in response to BK was significantly blunted (~30%) in the adults with elevated BP (from -1.2±0.8 to 50.2±4.8 ng/100mL tissue/min) compared with normal BP (from 0.9±3.4 to 73.0±8.0 ng/100mL tissue/min); and total t-PA release (area under the BK curve) was ~25% lower (p<0.05) in the adults with elevated (307±33 ng/100mL tissue) vs. normal (396±27 ng/100mL tissue) BP. Importantly, net endothelial release rate (from -1.5±1.0 to 40.6±4.3 ng/100mL tissue/min) and total amount of t-PA released (222±28 ng/100mL tissue) in response to BK were markedly lower (~25% and 30%, respectively, P<0.05) in the elevated BP and short sleep duration group compared with the elevated BP and normal sleep duration group. In the elevated BP population, sleep duration was positively correlated with total t-PA release (r=0.46, P<0.05). There was no effect of SNP on t-PA release in any group. In summary, insufficient sleep is associated with exacerbated impairments in t-PA release in adults with elevated BP.

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Abstract 28: Regular Aerobic Exercise Counteracts Endothelial Vasomotor Dysfunction Associated With Insufficient Sleep

Circulation ◽

10.1161/circ.141.suppl_1.28 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Kelly A Stockelman ◽

Anthony R Bain ◽

Caitlin A Dow ◽

Jared J Greiner ◽

Brian L Stauffer ◽

...

Keyword(s):

Exercise Training ◽

Aerobic Exercise ◽

Sleep Duration ◽

Middle Aged ◽

Short Sleep Duration ◽

Insufficient Sleep ◽

Short Sleep ◽

Vasomotor Regulation ◽

Normal Sleep ◽

Middle Aged Adults

Insufficient sleep, defined as chronic short sleep duration (<7 h/night), is an independent risk factor for cardiovascular disease (CVD). We have previously demonstrated that insufficient sleep is associated with reduced endothelium-dependent vasodilation and enhanced endothelin (ET)-1-mediated vasoconstrictor tone. Impaired endothelial vasomotor regulation is thought to contribute mechanistically to the increased risk of atherosclerotic vascular disease incurred with chronic insufficient sleep. Regular aerobic exercise is an effective lifestyle strategy for improving endothelial function and, in turn reducing cardiovascular risk. It is currently unknown if regular aerobic exercise can counteract the negative impact of insufficient sleep on endothelial vasomotor regulation. We tested the hypotheses that regular aerobic exercise would: 1) improve endothelial vasodilation; and 2) decrease ET-1-mediated vasoconstrictor tone in middle-aged adults who chronically sleep less than 7 h/night. We studied 36 healthy, middle-aged adults: 16 with normal sleep duration (10M/6F; age: 57±2 yr; sleep duration: 7.4±0.1 h/night) and 20 with short sleep duration (11M/9F; 56±1 yr; sleep duration: 6.2±0.1 h/night). The 20 short sleepers completed a 3-month aerobic exercise training intervention. Forearm blood flow (FBF; plethysmography) was determined in response to intra-arterial doses of acetylcholine (ACh), sodium nitroprusside (SNP), BQ-123 (ET A receptor antagonist) and ACh + BQ-123 in both groups and after the exercise intervention in the short sleepers. As expected, forearm vasodilator responses to ACh were lower (20%; P<0.05) in the short (from 4.2±0.2 to 10.5±0.6 mL/100 mL tissue/min) vs normal (4.2±0.2 to 12.7±0.6 mL/100 mL tissue/min) sleepers. FBF responses to SNP were comparable between the groups. In response to BQ-123, short sleep group had a greater increase in resting FBF than normal sleep group (~25% vs ~8%; P< 0.05). ACh+BQ-123 resulted in an ~25% increase in the ACh-vasodilation in the short sleep group only. After exercise training, although nightly sleep duration was not affected (6.4±0.1 h/night), ACh-mediated vasodilation was ~20% higher (P<0.05), ET-1-mediated vasoconstriction was ~90% lower (P<0.05) and vasodilator response to ACh was not significantly increased with ET A receptor blockade. These results indicate that regular aerobic exercise can reverse the negative influence of insufficient sleep on endothelial vasomotor function, independent of changes in nightly sleep duration.

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Insomnia with objective short sleep duration is associated with longer duration of insomnia in the Freiburg Insomnia Cohort compared to insomnia with normal sleep duration, but not with hypertension

PLoS ONE ◽

10.1371/journal.pone.0180339 ◽

2017 ◽

Vol 12 (7) ◽

pp. e0180339 ◽

Cited By ~ 21

Author(s):

Anna F. Johann ◽

Elisabeth Hertenstein ◽

Simon D. Kyle ◽

Chiara Baglioni ◽

Bernd Feige ◽

...

Keyword(s):

Sleep Duration ◽

Short Sleep Duration ◽

Short Sleep ◽

Normal Sleep

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Associations between fecal short-chain fatty acids and sleep continuity in older adults with insomnia symptoms

Scientific Reports ◽

10.1038/s41598-021-83389-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Faiga Magzal ◽

Carmel Even ◽

Iris Haimov ◽

Maayan Agmon ◽

Kfir Asraf ◽

...

Keyword(s):

Older Adults ◽

Fatty Acids ◽

Sleep Duration ◽

Sleep Onset ◽

Short Chain Fatty Acids ◽

Short Sleep Duration ◽

Short Sleep ◽

Sleep Continuity ◽

Normal Sleep ◽

Insomnia Symptoms

AbstractInsomnia is a disorder characterized by difficulty falling asleep and poor sleep continuity and is associated with increased risks for physical and cognitive decline. Insomnia with short sleep duration is considered the most biologically severe phenotype of the disorder. Evidence suggests that short-chain fatty acids (SCFAs), the main byproducts of fiber fermentation in the gut, may affect sleep via gut–brain communications. This study explores associations between SCFAs and sleep continuity and compares SCFA concentrations in short vs. normal sleep insomnia phenotypes in older adults. Fifty-nine participants with insomnia symptoms (≥ 65 years), completed 2 weeks of objective sleep monitoring (actigraphy), and were divided into short and normal sleep duration phenotypes via cluster analysis. Sleep measures included total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), and wake after sleep onset (WASO). Stool samples were collected and fecal SCFA concentrations were determined by gas-chromatography-mass-spectrometry (GCMS). Higher concentrations of acetate, butyrate, and propionate, and total SCFAs, were associated with lower SE and longer SOL after controlling for Body Mass Index (BMI). Concentrations were higher in the short sleep duration phenotype. Age, BMI, TST, and SOL explained 40.7% of the variance in total SCFAs. Findings contribute to understanding pathways along the gut–brain axis and may lead to the use of SCFAs as biomarkers of insomnia phenotypes.

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Regular Aerobic Exercise Counteracts Endothelial Vasomotor Dysfunction Associated With Insufficient Sleep

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00615.2020 ◽

2021 ◽

Author(s):

Kelly A. Stockelman ◽

Anthony R. Bain ◽

Caitlin A. Dow ◽

Kyle J. Diehl ◽

Jared J. Greiner ◽

...

Keyword(s):

Blood Flow ◽

Cardiovascular Risk ◽

Aerobic Exercise ◽

Sleep Duration ◽

Forearm Blood Flow ◽

Insufficient Sleep ◽

Short Sleep ◽

Normal Sleep ◽

Middle Aged Adults ◽

Vasomotor Dysfunction

Insufficient sleep is associated with endothelial vasomotor dysfunction and increased cardiovascular risk. Regular aerobic exercise is an effective lifestyle strategy for improving endothelial function and, in turn, reducing cardiovascular risk. We tested the hypotheses that regular aerobic exercise would: 1) improve endothelial vasodilation; and 2) decrease ET-1-mediated vasoconstrictor tone in middle-aged adults who chronically sleep <7 h/night. Thirty-six healthy, middle-aged adults were studied: 16 with normal sleep duration (age: 57±2 yr; sleep duration: 7.4±0.1 h/night) and 20 with short sleep duration (56±1 yr; 6.2±0.1 h/night). The 20 short sleepers completed a 3-month aerobic exercise training intervention. Forearm blood flow was determined (via plethysmography) in response to intra-arterial acetylcholine (ACh), BQ-123 (ETAreceptor antagonist), ACh+BQ-123 and sodium nitroprusside. Forearm blood flow responses to ACh were lower (20%; P<0.05) in the short (from 4.2±0.2 to 10.5±0.6 mL/100 mL tissue/min) vs normal (4.2±0.2 to 12.7±0.6 mL/100 mL tissue/min) sleepers. In response to BQ-123, the short sleep group had a significantly greater increase in resting forearm blood flow than the normal sleep group (~25% vs ~8%). ACh+BQ-123 resulted in a significant (~25%) increase in the ACh-vasodilation in the short sleep group only. After exercise training, although nightly sleep duration was unchanged (6.4±0.1 h/night), ACh-mediated vasodilation was significantly higher (~20%), ET-1-mediated vasoconstriction was significantly lower (~80%) and the vasodilator response to ACh was not increased with ETAreceptor blockade. Regular aerobic exercise, independent of changes in nightly sleep duration, can counteract insufficient sleep-related endothelial vasomotor dysfunction.

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Considering Psychosocial Factors When Investigating Blood Pressure in Patients with Short Sleep Duration: A Propensity Score Matched Analysis

International Journal of Hypertension ◽

10.1155/2021/7028942 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Ningjing Qian ◽

Dandan Yang ◽

Huajun Li ◽

Siyin Ding ◽

Xia Yu ◽

...

Keyword(s):

Blood Pressure ◽

Propensity Score ◽

Propensity Score Matching ◽

Psychosocial Factors ◽

Sleep Duration ◽

Psychosocial Characteristics ◽

Short Sleep Duration ◽

Short Sleep ◽

Before And After ◽

Normal Sleep

Few studies have considered psychosocial characteristics when investigating the associations between sleep duration and blood pressure (BP). In this study, we took propensity score matching (PSM) to adjust for psychosocial characteristics when comparing BP between individuals with short sleep duration and those with normal sleep duration. A total of 429 participants were included. 72 participants with sleep duration ≤6 h and 65 participants with sleep duration >6 h were matched after PSM. We compared office BP, 24-hour BP, and prevalence of hypertension in the populations before and after PSM, respectively. In the unmatched population, participants with sleep duration ≤6 h were observed with higher office diastolic BP (DBP) and 24-h systolic BP (SBP)/DBP (all P < 0.05 ). In the matched populations, the differences between the two groups (sleep duration ≤6 h vs. sleep duration >6 h) in office DBP (88.4 ± 10.9 vs. 82.5 ± 11.1 mm Hg; P = 0.002 ), 24-h SBP (134.7 ± 12.0 vs. 129.3 ± 11.6 mm Hg; P = 0.009 ), and 24-h DBP (83.4 ± 9.9 vs. 78.1 ± 10.1 mm Hg; P = 0.002 ) become more significant. Participants with sleep duration ≤6 h only show higher prevalence of hypertension based on 24-h BP data, while analysis after PSM further revealed that these with sleep duration ≤6 h presented about 20% higher prevalence of elevated BP up to office diagnosed hypertension threshold. Therefore, psychosocial characteristics accompanied with short sleep duration should be fully valued in individuals at risks for elevated BP. This trial is registered with NCT03866226.

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