Prolonged Wakefulness: Lack of Sufficient Duration of Sleep as a Risk Factor for Cardiovascular Diseases – – Indications for Cardiovascular Chrono-therapeutics
Curator: Aviva Lev-Ari, PhD, RN
This article has the following structure:
- Sleep Drives Metabolite Clearance from the Adult Brain
- Sleep and Cardiovascular Disease
- Sleep Duration as a Risk Factor for Cardiovascular Disease – a Review of the Recent Literature
- The Society for Cardiovascular Angiography and Interventions: Poor sleep has been linked to CVD Biomarkers
- Hemostatic Alterations in Patients With Obstructive Sleep Apnea and the Implications for Cardiovascular Disease*
- Elevated C-Reactive Protein in Patients With Obstructive Sleep Apnea
- SOURCES on Sleep in Science
- REFERENCES on Sleep Deprivation, Physiological Processes and Cardiovascular Diseases
Vol. 342 no. 6156 pp. 373-377
DOI: 10.1126/science.1241224
Sleep Drives Metabolite Clearance from the Adult Brain
- Lulu Xie1,*,
- Hongyi Kang1,*,
- Qiwu Xu1,
- Michael J. Chen1,
- Yonghong Liao1,
- Meenakshisundaram Thiyagarajan1,
- John O’Donnell1,
- Daniel J. Christensen1,
- Charles Nicholson2,
- Jeffrey J. Iliff1,
- Takahiro Takano1,
- Rashid Deane1,
- Maiken Nedergaard1,†
+Author Affiliations
1Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.
2Department of Neuroscience and Physiology, Langone Medical Center, New York University, New York, NY 10016, USA.
- ↵†Corresponding author. E-mail: nedergaard@urmc.rochester.edu
-
↵* These authors contributed equally to this work.
The conservation of sleep across all animal species suggests that sleep serves a vital function. We here report that sleep has a critical function in ensuring metabolic homeostasis. Using real-time assessments of tetramethylammonium diffusion and two-photon imaging in live mice, we show that natural sleep or anesthesia are associated with a 60% increase in the interstitial space, resulting in a striking increase in convective exchange of cerebrospinal fluid with interstitial fluid. In turn, convective fluxes of interstitial fluid increased the rate of β-amyloid clearance during sleep. Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.
Figure Source: Goodnight. Sleep Clean.
By MARIA KONNIKOVA JAN. 11, 2014
http://www.nytimes.com/2014/01/12/opinion/sunday/goodnight-sleep-clean.html?emc=eta1&_r=0
Concepts presented in this article about Sleep
- Maiken Nedergaard, a Danish biologist who has been leading research into sleep function at the University of Rochester’s medical school, told me. “It has to have a basic evolutional function. Otherwise it would have been eliminated.”
- sleep is essential for forming and consolidating memories and that it plays a central role in the formation of new neuronal connections and the pruning of old ones.
- Sleep, may play a crucial role in our brain’s physiological maintenance
- Dr. Nedergaard proposed a brain equivalent of the lymphatic system, a network of channels that cleared out toxins with watery cerebrospinal fluid. She called it the glymphatic system, a nod to its dependence on glial cells (the supportive cells in the brain that work largely to maintain homeostasis and protect neurons) and its function as a sort of parallel lymphatic system.
- the brain’s interstitial space — the fluid-filled area between tissue cells that takes up about 20 percent of the brain’s total volume — was mainly dedicated to physically removing the cells’ daily waste.
- When the mouse brain is sleeping or under anesthesia, it’s busy cleaning out the waste that accumulated while it was awake.
- “We saw almost no inflow of cerebrospinal fluid into the brain when the mice were awake, but then when we anesthetized them, it started flowing. It’s such a big difference I kept being afraid something was wrong,” says Dr. Nedergaard.
- Not in Humans yet, So far the glymphatic system has been identified as the neural housekeeper in baboons, dogs and goats. “If anything,” Dr. Nedergaard says, “it’s more needed in a bigger brain.”
- According to the National Sleep Foundation, adults should sleep seven to nine hours. On average, we’re getting one to two hours less sleep a night than we did 50 to 100 years ago and 38 minutes less on weeknights than we did as little as 10 years ago. Between 50 and 70 million people in the United States suffer from some form of chronic sleep disorder.
- At the University of Pennsylvania’s Center for Sleep and Circadian Neurobiology, Sigrid Veasey has been focusing on precisely how restless nights disturb the brain’s normal metabolism. What happens to our cognitive function when the trash piles up?
- The faster the fluids clear the decks, the more effectively the brain’s metabolism is functioning.
Consequences of Lack of Sufficient Duration of Sleep
- the acceleration of neurodegenerative diseases like Alzheimer’s and Parkinson’s. While we don’t know whether sleep loss causes the disease, or the disease itself leads to sleep loss. there is a buildup of the types of proteins that the glymphatic system normally clears out during regular sleep, like beta-amyloids and tau, both associated with Alzheimer’s and other types of dementia.
- sleep deprivation, as everyone who has experienced it knows, impedes our ability to concentrate, to pay attention to our environment and to analyze information creatively.
- brains can recover quite readily from short-term sleep loss, chronic prolonged wakefulness and sleep disruption stresses the brain’s metabolism.
- degeneration of key neurons involved in alertness and proper cortical function and a buildup of proteins associated with aging and neural degeneration.
- Recovery from sleep loss is slower than we’d thought,” Dr. Veasey notes.
- mpaired clearance in the awake brain: skipping sleep does irreparable damage to the brain, prematurely aging it or setting it up for heightened vulnerability to other insults.
- work longer hours, become more stressed, sleep less, impair our brain’s ability to clean up after all that hard work, and become even less able to sleep soundly
- there’s no evidence that aided sleep is as effective as natural sleep.
New directions for Drug Development
Future drug interventions could focus directly on the glymphatic system, to promote the enhanced cleaning power of the sleeping brain in a brain that is fully awake. One day, scientists might be able to successfully mimic the expansion of the interstitial space that does the mental janitorial work so that we can achieve maximally efficient round-the-clock brain trash pickup.
Sleep and cardiovascular disease
Wolk R, Gami AS, Garcia-Touchard A, Somers VK.
Abstract
Sleep is an important modulator of cardiovascular function, both in physiological conditions and in disease states.
In individuals without a primary sleep disorder Sleep may exert significant effects on the
- autonomic nervous system,
- systemic hemodynamics,
- cardiac function,
- endothelial function, and
- coagulation.
Some of these influences can be directly linked to specific modulatory effects of sleep stages per se; others result from the natural circadian rhythm of various physiological processes.
There is a temporal association between physiological sleep and
- occurrence of vascular events,
- cardiac arrhythmias, and
- sudden death.
Epidemiological and pathophysiological studies also indicate that there may be a causal link between
- primary sleep abnormalities (sleep curtailment, shift work, and sleep-disordered breathing) and
- cardiovascular and metabolic disease, such as hypertension, atherosclerosis, stroke, heart failure, cardiac arrhythmias, sudden death, obesity, and the metabolic syndrome.
Finally, sleep disturbances may occur as a result of several medical conditions (including obesity, chronic heart failure, and menopause) and may therefore contribute to cardiovascular morbidity associated with these conditions. Further understanding of specific pathophysiological pathways linking sleep disorders to cardiovascular disease is important for developing therapeutic strategies and may have important implications for cardiovascular chronotherapeutics.
Sleep Duration as a Risk Factor for Cardiovascular Disease- a Review of the Recent Literature
Michiaki Nagai,1,2 Satoshi Hoshide,1 and Kazuomi Kario1,*
Sleep loss is a common condition in developed countries, with evidence showing that people in Western countries are sleeping on average only 6.8 hour (hr) per night, 1.5 hr less than a century ago. Although the effects of sleep deprivation on our organs have been obscure, recent epidemiological studies have revealed relationships between sleep deprivation and hypertension (HT), coronary heart disease (CHD), and diabetes mellitus (DM). This review article summarizes the literature on these relationships. Because sleep deprivation increases sympathetic nervous system activity, this increased activity serves as a common pathophysiology for HT and DM. Adequate sleep duration may be important for preventing cardiovascular diseases in modern society.
The Society for Cardiovascular Angiography and Interventions: Poor sleep has been linked to
- high blood pressure,
- atherosclerosis (clogging or hardening of the arteries),
- heart failure,
- heart attack,
- stroke,
- diabetes, and
- obesity.
Poor sleep appears to increase substances in your body, such as c-reactive protein, that indicate inflammation is a problem. So, inflammation, which is how the body responds to injury, infection or disease, may be part of the reason poor sleep affects your cardiovascular system. Poor sleep also causes the body to produce more stress hormones, which may contribute to cardiovascular disease.
On the other hand, sometimes symptoms related to cardiovascular disease can be a cause of poor sleep. Angina (chest pain), arrhythmias (abnormal heart rhythms), sleep apnea (a series of breathing pauses during sleep that stress your cardiovascular system), and fluid build-up in the lungs due to heart failure may all disrupt sleep.
The good news is there are steps you can take to improve your sleep. Always talk to your doctor about your sleep problems, however minor you think they might be. There may be lifestyle changes or treatments that can help you sleep better. And read on, so SecondsCount.org can help you improve the quality of sleep you get.
http://www.scai.org/SecondsCount/Treatment/HealthyLiving/SleepandCardiovascularDisease.aspx
Hemostatic Alterations in Patients With Obstructive Sleep Apnea and the Implications for Cardiovascular Disease*
Study objectives: Patients with obstructive sleep apnea (OSA) are at increased risk for coronary artery and cerebrovascular diseases. Numerous studies suggest that a hypercoagulable state is prospectively related to atherothrombotic events. This review explores whether changes in hemostasis may constitute one biological link between OSA and vascular disease.
Design: Ten studies on hemostatic variables in OSA were located by electronic library search and descriptively reviewed. Work on hemostatic function with physiologic conditions similar to those found in OSA (hypoxemia and hyperactivity of the sympathetic nervous system) was considered to discuss potential molecular mechanisms of procoagulant disturbances in OSA.
Measurements and results: The reviewed data suggest that, as compared to non-OSA control subjects, patients with OSA have elevated plasma fibrinogen levels, exaggerated platelet activity, and reduced fibrinolytic capacity. Although not consistently shown, severity of OSA (ie, apnea-hypopnea index) and plasma epinephrine were independent predictors of platelet activity, and average minimal oxygen saturation was an independent predictor of fibrinogen. In some studies, treatment with continuous positive airway pressure decreased platelet activity, plasma fibrinogen levels, and activity of clotting factor VII.
Conclusions: There is some evidence for a hypercoagulable state in OSA, which might help explain the increased prevalence of vascular diseases in this population. To further confirm such a notion, future studies need to be performed on sufficiently large samples to be able to control for confounders of hemostatic activity. Prospective studies are needed to examine the association between hemostasis molecules and strong vascular end points.
Elevated C-Reactive Protein in Patients With Obstructive Sleep Apnea
Circulation.2002; 105: 2462-2464
- Abu S.M. Shamsuzzaman, MBBS, PhD;
- Mikolaj Winnicki, MD, PhD;
- Paola Lanfranchi, MD;
- Robert Wolk, MD, PhD;
- Tomas Kara, MD;
- Valentina Accurso, MD;
- Virend K. Somers, MD, PhD
+Author Affiliations
- Correspondence to Virend K Somers, MD, DPhil, Divisions of Hypertension and Cardiovascular Diseases, Mayo Clinic Rochester, 200 First St, SW, Rochester, MN 55905. E-mail somers.virend@mayo.edu
Abstract
Background— Obstructive sleep apnea (OSA) has been increasingly linked to cardiovascular and cerebrovascular disease. Inflammatory processes associated with OSA may contribute to cardiovascular morbidity in these patients. We tested the hypothesis that OSA patients have increased plasma C-reactive protein (CRP).
Methods and Results— We studied 22 patients (18 males and 4 females) with newly diagnosed OSA, who were free of other diseases, had never been treated for OSA, and were taking no medications. We compared CRP measurements in these patients to measurements obtained in 20 control subjects (15 males and 5 females) who were matched for age and body mass index, and in whom occult OSA was excluded. Plasma CRP levels were significantly higher in patients with OSA than in controls (median [range] 0.33 [0.09 to 2.73] versus 0.09 [0.02 to 0.9] mg/dL, P<0.0003). In multivariate analysis, CRP levels were independently associated with OSA severity (F=6.8, P=0.032).
Conclusions— OSA is associated with elevated levels of CRP, a marker of inflammation and of cardiovascular risk. The severity of OSA is proportional to the CRP level.
SOURCE
SOURCES on Sleep in Science
Vol. 342 no. 6156 pp. 373-377
DOI: 10.1126/science.1241224
- REPORT
Sleep Drives Metabolite Clearance from the Adult Brain
- Lulu Xie1,*,
- Hongyi Kang1,*,
- Qiwu Xu1,
- Michael J. Chen1,
- Yonghong Liao1,
- Meenakshisundaram Thiyagarajan1,
- John O’Donnell1,
- Daniel J. Christensen1,
- Charles Nicholson2,
- Jeffrey J. Iliff1,
- Takahiro Takano1,
- Rashid Deane1,
- Maiken Nedergaard1,†
+Author Affiliations
1Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.
2Department of Neuroscience and Physiology, Langone Medical Center, New York University, New York, NY 10016, USA.
- ↵†Corresponding author. E-mail: nedergaard@urmc.rochester.edu
-
↵* These authors contributed equally to this work.
The conservation of sleep across all animal species suggests that sleep serves a vital function. We here report that sleep has a critical function in ensuring metabolic homeostasis. Using real-time assessments of tetramethylammonium diffusion and two-photon imaging in live mice, we show that natural sleep or anesthesia are associated with a 60% increase in the interstitial space, resulting in a striking increase in convective exchange of cerebrospinal fluid with interstitial fluid. In turn, convective fluxes of interstitial fluid increased the rate of β-amyloid clearance during sleep. Thus, the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.
- Received for publication 30 May 2013.
- Accepted for publication 28 August 2013.
The editors suggest the following Related Resources on Science sites In Science Magazine
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NEWS & ANALYSIS NEUROSCIENCE Sleep: The Brain’s Housekeeper?
- Emily Underwood
Science 18 October 2013: 301.
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PERSPECTIVE NEUROSCIENCE Sleep It Out
- Suzana Herculano-Houzel
Science 18 October 2013: 316-317.
In Science Translational Medicine
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RESEARCH ARTICLE OBESITY AND DIABETES Adverse Metabolic Consequences in Humans of Prolonged Sleep Restriction Combined with Circadian Disruption
- Orfeu M. Buxton,
- Sean W. Cain,
- Shawn P. O’Connor,
- James H. Porter,
- Jeanne F. Duffy,
- Wei Wang,
- Charles A. Czeisler,
- and Steven A. Shea
Sci Transl Med 11 April 2012: 129ra43.
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RESEARCH ARTICLE SLEEP Uncovering Residual Effects of Chronic Sleep Loss on Human Performance
- Daniel A. Cohen,
- Wei Wang,
- James K. Wyatt,
- Richard E. Kronauer,
- Derk-Jan Dijk,
- Charles A. Czeisler,
- and Elizabeth B. Klerman
Sci Transl Med 13 January 2010: 14ra3.
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
- Taking Out the Garbage During Sleep, and Alzheimer PathologyJournal Watch 2 December 2013: NA32813.
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Sleep and General Anesthesia Clear the Mouse Brain of Toxic MetabolitesJournal Watch 26 November 2013: NA32960.
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Cerebral Arterial Pulsation Drives Paravascular CSF-Interstitial Fluid Exchange in the Murine BrainJ. Neurosci. 13 November 2013: 18190-18199.
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Sleep It Out Science 18 October 2013: 316-317.
SOURCE
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