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The Cardivascular and Metabolic Effects of OSA

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The Cardivascular and Metabolic Effects of OSA

Postby Vicki » Sun Aug 14, 2011 7:10 am

Literature review updated August 14, 2011. I am slowly going through my backlog of OSA articles from PubMed and thought I would just go ahead and post what I have so far. I still have several months in 2010 to go and all of 2011. I accidently deleted some of the links and I am slowly putting them back in. But in the meantime, the article titles and dates are listed and you can do a PubMed search if you want to see more. Dark blue are active links, bright blue are not. Sorry about the inconvenience!!
Pubmed

This is a compilation of a few abstracts from selected peer reviewed basic research journal articles highlighting research in the role of Obstructive Sleep Apnea in cardiovascular and metabolic diseases such as congestive heart failure, stroke, arrhythmias, diabetes, metabolic syndrome, etc. There is one abstract from 1983 which was the first article published linking OSA and cardiac arrhythmias. I have organized these into three sections, I. Cardiovascular Effects of OSA. II. Metabolic Effects of OSA. III. Other Effects of OSA/Miscellaneous. Abstracts are listed most current to oldest.

Click on the "Full Text" link to the right of the abstract to see the complete article. Some abstracts link to the full length article for free while others require you to buy a download. Or, you can go to a medical library and retrieve the journal using the reference numbers. If you would like to see how I found these abstracts, put search terms of interest such as "obstructive AND sleep AND apnea AND congestive AND heart AND failure" into the search field in the U.S. National Library of Medicine PubMed link below. PubMed is where all peer reviewed and published research studies from around the world are archived. The U.S. National Library of Medicine is associated with the U.S. National Institutes of Health.
Pubmed

PM me if you have any questions. Vicki

Definitions

Proinflammatory Factors: Proteins found in the blood which are increased during inflammation and thought to be directly involved in cardiovascular disease. Some examples of proinflammatory factors are: C-Reactive Protein (CRP) and cytokines such as the Interleukins and Tumor Necrosis Factor.

Prothrombic Factors: Clotting factor proteins found in the blood such as fibrinogen.

Platelets: Blood cells which clump together and along with clotting factor proteins, form blood clots.

Adhesion Molecules: Proteins found on the surface of cells which contribute to cells interacting together.

Endothelial cells: Cells which line blood vessels.


I. Cardiovascular Effects of OSA

Obstructive sleep apnea: novel trigger and potential therapeutic target for cardiac arrhythmias. Expert Rev Cardiovasc Ther. 2010 Jul;8(7):981-94.

Sleep-disordered breathing and cardiovascular disorders. Respir Care. 2010 Oct;55(10):1322-32; discussion 1330-2

Obstructive sleep apnea: novel trigger and potential therapeutic target for cardiac arrhythmias. Expert Rev Cardiovasc Ther. 2010 Jul;8(7):981-94

Patients with severe obstructive sleep apnea syndrome and elevated high-sensitivity C-reactive protein need priority treatment. Otolaryngol Head Neck Surg. 2010 Jul;143(1):72-7[url]

[url=http://www.ncbi.nlm.nih.gov/pubmed/20656942] Endothelial dysfunction in the microcirculation of patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2010 Dec 15;182(12):1540-5. Epub 2010 Jul 23


Risk of stroke from sleep apnea in men and women. Expert Rev Neurother. 2010 Aug;10(8):1267-71.

Influence of obstructive sleep apnea on left ventricular mass and global function: sleep apnea and myocardial performance index. Heart Vessels. 2010 Sep;25(5):400-4. Epub 2010 Jul 31.[/url’

[url=http://www.ncbi.nlm.nih.gov/pubmed/19506314?ordinalpos=20&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]Vascular effects of intermittent hypoxia. 2009


Obstructive sleep apnea and cardiovascular disease. 2009 Jun 6

Obstructive sleep apnea associated with erectile dysfunction and cardiovascular disease. 2009 Jun

Cardiovascular disease in obstructive sleep apnoea syndrome: the role of intermittent hypoxia and inflammation. 2009 May

Sleep-disordered breathing and acute stroke. 2009 April 3
CONCLUSIONS: "SDB is associated with cerebrovascular morbidity and an unfavorable clinical course. The presence of SDB should be systematically screened in patients with acute stroke. Further studies are needed to determine whether continuous positive airway pressure treatment ameliorates stroke outcome and prognosis."

Left atrial diameter is independently associated with arterial stiffness in patients with obstructive sleep apnea: Potential implications for atrial fibrillation. 2009 Feb 9
CONCLUSIONS: "Left atrial diameter is significantly increased and independently associated with arterial stiffness in patients with OSA. This potential mechanism of atrial remodeling may contribute to explain the increase risk of atrial fibrillation in these patients.

Effects of continuous positive airway pressure on cardiovascular risk profile in patients with severe obstructive sleep apnea and metabolic syndrome. 2008 Oct
CONCLUSIONS: “In patients with severe OSA and metabolic syndrome, good compliance to CPAP may improve insulin sensitivity, reduce systemic inflammation and oxidative stress, and reduce the global CVD risk.

Biology of peripheral blood cells in obstructive sleep apnea--the tip of the iceberg. 2008 Oct.
CONCLUSIONS: “The hallmark of sleep apnea--the multiple cycles of hypoxia/reoxygenation--promote oxidative stress and inflammation. These facilitate increased interactions of blood cells with endothelial cells, resulting in endothelial cell injury and dysfunction. Such events can promote atherosclerosis and the development of cardiovascular morbidities in OSA.”

Obstructive sleep apnea syndrome is a systemic disease. Current evidence, 2008 Oct
CONCLUSIONS: “Although the etiology of OSAS is uncertain, intense local and systemic inflammation is present. A variety of phenomena are implicated in this disease such as modifications in the autonomic nervous system, hypoxemia-reoxygenation cycles, inflammation, and coagulation-fibrinolysis imbalance. OSAS patients also present increased levels of certain biomarkers linked to endocrine-metabolic and cardiovascular alterations among other systemic consequences. All of this indicates that, more than a local abnormality, OSAS should be considered a systemic disease.”

Cardiac arrhythmias in obstructive sleep apnea. 2008 Oct

Obstructive sleep apnea: the new cardiovascular disease. Part I: obstructive sleep apnea and the pathogenesis of vascular disease. 2008 Sep 20

Implications of Obstructive Sleep Apnea for Atrial Fibrillation and Sudden Cardiac Death, 2008 Sept

Sleep apnea and cardiovascular disease: an American Heart Association/american College Of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council On Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). September, 2008.

Brain Structural Changes in Obstructive Sleep Apnea, 2008, July 1
CONCLUSIONS: "White matter is extensively affected in OSA patients; the alterations include axons linking major structures within the limbic system, pons, frontal, temporal and parietal cortices, and projections to and from the cerebellum."

Body Mass Index, Obstructive Sleep Apnea, and Outcomes of Catheter Ablation of Atrial Fibrillation, 2008 July.

Comparison of Serum Adiponectin and Tumor Necrosis Factor-Alpha Levels between Patients with and without Obstructive Sleep Apnea Syndrome, 2008 May.Conclusion: Serum adiponectin is significantly lower in patients with OSAS and it is independent of obesity. This might explain the high incidence of CVD and metabolic syndrome in patients with OSAS.
Definition from MedicineNet.com: Adiponectin: A protein hormone produced and secreted exclusively by adipocytes (fat cells) that regulates the metabolism of lipids and glucose. Adiponectin influences the body's response to insulin. Adiponectin also has anti-inflammatory effects on the cells lining the walls of blood vessels. High blood levels of adiponectin are associated with a reduced risk of heart attack. Low levels of adiponectin are found in people who are obese (and who are at increased risk of a heart attack). Adipocytes produce and secrete a number of proteins, including leptin, adipsin, properdin, and tumor necrosis factor (TNF).

Left ventricular diastolic dysfunction is linked to severity of obstructive sleep apnoea. Eur Respir J. 2010 Dec;36(6):1323-9. Epub 2010 Jun 18

Anadolu Kardiyol Derg. 2010 Feb;10(1):75-80[/url}

[url=http://www.ncbi.nlm.nih.gov/pubmed/18416854?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum]The underlying mechanisms for development of hypertension in the metabolic syndrome, 2008 April.


Arrhythmias in patients with obstructive sleep apnea, 2008 March.

The current prevalence of sleep disordered breathing in congestive heart failure patients treated with beta-blockers, 2008 Feb.

Obstructive Sleep Apnea Is Risk Factor for Death in Stroke Patients, 2008 February.

Sleep-disordered breathing and chronic atrial fibrillation, 2008 Feb.

Diagnosis and treatment of sleep apnea in heart disease, 2007 Dec.

Decreased right and left ventricular myocardial performance in obstructive sleep apnea. 2007 Dec.
CONCLUSIONS: OSA, particularly when moderate to severe, is associated with impaired right and left ventricular function and increased left atrial volume. These findings support the notion that OSA may contribute to the development of atrial fibrillation and CHF.

Long-term effect of continuous positive airway pressure on BP in patients with hypertension and sleep apnea. 2007 Dec.

Silent Brain Infarction and Platelet Activation in Obstructive Sleep Apnea, 2007 March 15. ]
Two proteins which are involved in binding platelets (cell fragments which are a part of the clotting process) to cells, and thus contribute to atherosclerosis, are found in increased levels in people with OSA. This is another mechanism that OSA contributes to cardiovascular disease and stroke. Additionally, CPAP therapy decreases the levels of these proteins. There are many other references in this article.

Brain Death by a Thousand Hypoxic Cuts in Sleep, 2007 March 15.
How OSA causes irreversible dementia. Includes a review of the "Silent Brain Infarction and Platelet Activation in OSA" article above.

Intermittent hypoxia and cognitive function: implications from chronic animal models. 2007

Continuous positive airway pressure treatment for sleep apnea in older adults, 2007 Jan 31.
These studies have demonstrated that following CPAP therapy, older adults have increased alertness, improved neurobehavioral outcomes in cognitive processing, memory, and executive function, decreased sleep disruption from nocturia and a positive effect on factors affecting cardiac function, including vascular resistance, platelet coagulability and other aspects of cardiovascular health. Describes the positive effect of CPAP therapy.

Sleep Apnea in Hypertension, 2006.

Obstructive sleep apnea and cardiovascular disease, 2006 Dec 3.
Overview. Describes the positive effect of CPAP therapy.

Sleepiness in obstructive sleep apnea: a harbinger of impaired cardiac function? 2006 Dec 1
CONCLUSIONS: These results suggest that daytime sleepiness is independently associated with decreases in cardiac function as assessed by impedance cardiography in patients with obstructive sleep apnea.

A review of neuroimaging in obstructive sleep apnea. October 15, 2006

Sleep Apnea Increases Cardiac Arrhythmia Risk, 2006 April 15

Early signs of atherosclerosis in obstructive sleep apnea, 2005 Sep 1
CONCLUSIONS: Middle-aged patients with OSA who are free of overt cardiovascular diseases have early signs of atherosclerosis. All vascular abnormalities correlated significantly with the severity of the OSA, which further supports the hypothesis that OSA plays an independent role in atherosclerosis progression.

Inducible nitric oxide synthase in long-term intermittent hypoxia: hypersomnolence and brain injury, 2005 Jun 15
Nitrous oxide is also involved in the inflammatory response. This was a mouse study showing that hypoxia causes an increase in the enzyme which forms nitrous oxide, nitrous oxide synthase which would cause an increased inflammatory response.

Repetitive hypoxia increases lipid loading in human macrophages-a potentially atherogenic effect, 2005 April
In this in vitro (out of body) study, blood cells called macrophages (the scavengers of our immune system) were found to gobble up more lipids (fat) when exposed to hypoxia (decreased O2 levels). This increase in intracellular lipids made the macrophages stick better to umbilical vein endothelial cells. This suggests that hypoxia in OSA might cause macrophages to get fat increasing the tendency for them to stick to the endothelial cells of the vasculature, contributing to plaque formation and cardiovascular disease.

Sleep apnea syndromes and cardiovascular disease, 2005 March
A very brief and concise review of the possible causes of vascular disease due to OSA. Describes the positive effect of CPAP therapy.

Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. 2005 March 19 Have OSA and don't use a CPAP, get cardiovascular disease. Use a CPAP decrease your risk.

The Cardiac Consequences of the Obstructive Sleep Apnea-Hypopnea Syndrome, 2005 January. pdf file
A Cardiology Grand Rounds presentation to the Department of Medicine at Mount Sinai, NY. Nice summary of OSA effects including arrhythmias, immunological and vascular effects.

Changes in extracranial arteries in obstructive sleep apnoea, 2005 Jan
35 normal and 35 OSA patients were studied for carotid artery wall thickening and extracranial vessel stenosis (hardening) and plaque formation. Patients were studied blind (meaning the researchers did not know their OSA status). OSA patients had significantly thicker carotid arteries and extracranial vessel stenosis and plaque formation.

Cardiopulmonary responses to exercise in moderate-to-severe obstructive sleep apnea, 2005
The authors concluded "that moderate-to-severe OSA patients have impaired exercise capacity. Exercise limitation seems to originate from cardiovascular reasons namely left ventricular dysfunction and/or peripheral vascular impairment."

The vascular micromilieu in obstructive sleep apnoea, 2005
Another brief and very detailed description of the various factors involved in disruption of the vascular system in OSA.
Additionally, this study describes the reversal of some of these effects by CPAP therapy.

Night-time and diastolic hypertension are common and underestimated conditions in newly diagnosed apnoeic patients, 2005 March
The conclusion of this study is that newly diagnosed OSA patients should be checked for hypertension because it is under diagnosed in OSA.

Association of obstructive sleep apnea and stenotic artery disease in ischemic stroke patients, 2003 August
The purpose of this study was to assess the "association between OSA and extracranial artery disease (EAD) as well as peripheral artery disease (PAD) in stroke survivors."
The authors stated that, "Our results support the hypothesis that OSA is associated with atherosclerosis and may contribute to ischemic stroke and PAD."

Hypertension, cardiac arrhythmias, myocardial infarction, and stroke in relation to obstructive sleep apnea, 1992 Sept

Intracranial pressure and obstructive sleep apnea, 1989.

Cardiac arrhythmia and conduction disturbances during sleep in 400 patients with sleep apnea syndrome, 1983 Sept.
The first study linking arrhythmia with Obstructive Sleep Apnea.

For articles on cardiomyopathy, go to :
Pubmed query field
and put "cardiomyopathy obstructive sleep apnea" into the search field


II. Metabolic Effects of OSA
APAP impact on metabolic syndrome in obstructive sleep apnea patients. Sleep Breath. 2010 Sep 24.

Sleep & the metabolic syndrome. Indian J Med Res. 2010 Feb;131:206-16.

If an article was about cardiovascular disease and metabolic disease, I put it in the Cardiovascular section above. Therefore, there are several articles about OSA and metabolic syndrome up there.
The impact of obstructive sleep apnea on metabolic and inflammatory markers in consecutive patients with metabolic syndrome. PLoS One. 2010 Aug 11;5(8):e12065

[url=http://www.ncbi.nlm.nih.gov/pubmed/20723141[Obstructive sleep apnoea is associated with risk factors comprising the metabolic syndrome. Respirology. 2010 Oct;15(7):1122-6. doi: 10.1111/j.1440-1843.2010.01818.x. Epub 2010 Aug 16[/url][url=http://www.ncbi.nlm.nih.gov/pubmed/20477311] Obstructive sleep apnea and the metabolic syndrome. Expert Rev Respir Med. 2009 Apr;3(2):177-86[/url]

Sleep, sleep-disordered breathing and metabolic consequences. July 2009

Metabolic consequences of sleep-disordered breathing. 2009

Obstructive sleep apnea is highly prevalent and correlates with impaired glycemic control in consecutive patients with the metabolic syndrome. 2009 Spring

Insulin Resistance And Daytime Sleepiness In Patients With Sleep Apnea, 2008 June.
CONCLUSIONS: Excessive daytime sleepiness (EDS) in OSAS is associated with insulin resistance independently of obesity. Hence, EDS may be a useful clinical marker to identify patients with OSAS at risk of metabolic syndrome.

Obstructive sleep apnea and type 2 diabetes: interacting epidemics, 2008 Feb.

Intermittent hypoxia reverses the diurnal glucose rhythm and causes pancreatic {beta}-cell replication in mice, 2008 Feb 1.
This mouse study suggests that during intermittent hypoxia in the presence of glucose, the beta-cells of the pancreas (which produce insulin) are susceptible to cell death which may be the mechanism linking OSA to Type II Diabetes.

The metabolic aspects and hormonal derangements in obstructive sleep apnoea syndrome and the role of CPAP therapy, 2006 Nov-Dec
This abstract starts, "Obstructive sleep apnea syndrome (OSAS) is part of a metabolic syndrome, whose main aspects are obesity, hypertension and diabetes, already incriminated for cardiovascular events."


III. Other Effects of OSA/Miscellaneous

Obstructive sleep apnea in chronic obstructive pulmonary disease patients. Curr Opin Pulm Med. 2011 Mar;17(2):79-83.

Obstructive sleep apnea in children. J Bras Pneumol. 2010 Jun;36 Suppl 2:57-61.[/ur;]

[url=http://www.ncbi.nlm.nih.gov/pubmed/20842037] Surgical treatment of obstructive sleep apnea: standard and emerging techniques. Curr Opin Pulm Med. 2010 Nov;16(6):552-8.


Central sleep apnea in patients with congestive heart failure Heart Fail Rev. 2009 Sep;14(3):135-41. Epub 2008 Aug 29.

The genetics of obstructive sleep apnoea. Curr Opin Pulm Med. 2010 Nov;16(6):536-42.

Central sleep apnea. Clin Chest Med. 2010 Jun;31(2):235-48

Encouraging CPAP adherence: it is everyone's job. Respir Care. 2010 Sep;55(9):1230-9

[url=http://www.ncbi.nlm.nih.gov/pubmed/20676805 The impact of obstructive sleep apnea on chronic kidney disease. Curr Hypertens Rep. 2010 Oct;12(5):378-83.[/url][url=http://www.ncbi.nlm.nih.gov/pubmed/20572424] An unusual cause of delirium. J Clin Sleep Med. 2010 Jun 15;6(3):290-1[/url]
Concomitant obstructive sleep apnea and chronic obstructive pulmonary disease: study design--the OLIN OSAS-COPD study. Clin Respir J. 2008 Oct;2 Suppl 1:120-2

Sleep apnea syndrome: central sleep apnea and pulmonary hypertension worsened during treatment with auto-CPAP, but improved by adaptive servo-ventilation. Intern Med. 2010;49(5):415-21. Epub 2010 Mar 1

Obstructive sleep apnea associated with erectile dysfunction and cardiovascular disease. 2009 Jun

Upper airway function in the pathogenesis of obstructive sleep apnea: a review of the current literature. November, 2008.
SUMMARY: "Ongoing studies are attempting to classify patients on the basis of the underlying pathophysiology. This work suggests that obstructive sleep apnea is a heterogeneous disease with multiple root causes. Ultimately, such a classification may allow more individualized treatment, not only relying on mechanical relief of the upper airway obstruction."

Neural alterations and depressive symptoms in obstructive sleep apnea patients. August, 2008

Leukoaraiosis and Ischemia. Beyond the myth. 2006 April 20
Leukoaraiosis (brain white matter lesions) are caused by hypoxia.

Periodic, profound peripheral vasoconstriction--a new marker of obstructive sleep apnea, 1999 Nov 1
The results of this study suggests that peripheral vascular changes in a finger tip can be used to diagnose OSA.

Vicki
Being defeated is often a temporary condition. Giving up is what makes it permanent.
Marilyn Vos Savant

That which does not kill you makes you stronger-Friedrich Nietzsche
Friedrich must of had apnea.
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Re: The Cardivascular and Metabolic Effects of OSA

Postby Izabela » Fri Nov 18, 2011 11:13 am

Very interesting. Thanks, Vicki.
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Re: The Cardivascular and Metabolic Effects of OSA

Postby Helfred » Sat May 19, 2012 11:11 am

Thanks looking for info and studies of sleep apnea causing ventricular tachyacardia. Any that you know of.
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Re: The Cardivascular and Metabolic Effects of OSA

Postby Vicki » Sun May 27, 2012 8:09 pm

Yes, here. Look for the papers that are pertinent:

http://www.ncbi.nlm.nih.gov/pubmed?term ... achycardia

Vicki
Being defeated is often a temporary condition. Giving up is what makes it permanent.
Marilyn Vos Savant

That which does not kill you makes you stronger-Friedrich Nietzsche
Friedrich must of had apnea.
User avatar
Vicki
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Posts: 6395
Joined: Tue May 31, 2005 8:21 pm
Location: Southern California
Machine: DeVilbiss IntelliPAP
Mask: Fisher & Paykel Flexifit 431
Humidifier: Rarely as needed
Year Diagnosed: 1999



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