Impaired cerebral autoregulation in obstructive sleep apnea.

Obstructive sleep apnea (OSA) increases the risk of stroke independent of known vascular and metabolic risk factors. Although patients with OSA have higher prevalence of hypertension and evidence of hypercoagulability, the mechanism of this increased risk is unknown. Obstructive apnea events are associated with surges in blood pressure, hypercapnia, and fluctuations in cerebral blood flow. These perturbations can adversely affect the cerebral circulation. We hypothesized that patients with OSA have impaired cerebral autoregulation, which may contribute to the increased risk of cerebral ischemia and stroke. We examined cerebral autoregulation in patients with and without OSA by measuring cerebral artery blood flow velocity (CBFV) by using transcranial Doppler ultrasound and arterial blood pressure using finger pulse photoplethysmography during orthostatic hypotension and recovery as well as during 5% CO(2) inhalation. Cerebral vascular conductance and reactivity were determined. Forty-eight subjects, 26 controls (age 41.0+/-2.3 yr) and 22 OSA (age 46.8+/-2.3 yr) free of cerebrovascular and active coronary artery disease participated in this study. OSA patients had a mean apnea-hypopnea index of 78.4+/-7.1 vs. 1.8+/-0.3 events/h in controls. The oxygen saturation during sleep was significantly lower in the OSA group (78+/-2%) vs. 91+/-1% in controls. The dynamic vascular analysis showed mean CBFV was significantly lower in OSA patients compared with controls (48+/-3 vs. 55+/-2 cm/s; P <0.05, respectively). The OSA group had a lower rate of recovery of cerebrovascular conductance for a given drop in blood pressure compared with controls (0.06+/-0.02 vs. 0.20+/-0.06 cm.s(-2).mmHg(-1); P <0.05). There was no difference in cerebrovascular vasodilatation in response to CO(2). The findings showed that patients with OSA have decreased CBFV at baseline and delayed cerebrovascular compensatory response to changes in blood pressure but not to CO(2). These perturbations may increase the risk of cerebral ischemia during obstructive apnea.

[1]  T. Young,et al.  Epidemiology of obstructive sleep apnea: a population health perspective. , 2002, American journal of respiratory and critical care medicine.

[2]  H. Yaggi,et al.  Obstructive sleep apnoea and stroke , 2004, The Lancet Neurology.

[3]  C. Caltagirone,et al.  Transcranial Doppler assessment of cerebrovascular reactivity in symptomatic and asymptomatic severe carotid stenosis. , 1996, Stroke.

[4]  K. Clark,et al.  Association of Sleep-Disordered Breathing, Sleep Apnea, and Hypertension in a Large Community- Based Study , 2000 .

[5]  P. Johnson,et al.  Autoregulation of Blood Flow , 1963, Science.

[6]  E B Ringelstein,et al.  Evaluation of Cerebral Vasomotor Reactivity by Various Vasodilating Stimuli: Comparison of CO2 to Acetazolamide , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[7]  Daniel J Buysse,et al.  Sleep–Related Breathing Disorders in Adults: Recommendations for Syndrome Definition and Measurement Techniques in Clinical Research , 2000 .

[8]  G. Beck,et al.  Transcranial Doppler assessment of cerebral perfusion reserve in patients with carotid occlusive disease and no evidence of cerebral infarction , 1993, Neurology.

[9]  G. Bernardi,et al.  Cerebral hemodynamic changes in sleep apnea syndrome and effect of continuous positive airway pressure treatment , 1998, Neurology.

[10]  G. Bernardi,et al.  Effect of Smoking on Cerebrovascular Reactivity , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[11]  S. Ameriso,et al.  Morning reduction of cerebral vasomotor reactivity , 1994, Neurology.

[12]  F. Faraci.  Oxidative stress: the curse that underlies cerebral vascular dysfunction? , 2005, Stroke.

[13]  E. Haus,et al.  Circadian Variation in Stroke Onset: Identical Temporal Pattern in Ischemic and Hemorrhagic Events , 2005, Chronobiology international.

[14]  Daniel J Buysse,et al.  Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. , 1999, Sleep.

[15]  R. Aaslid,et al.  Cerebral autoregulation dynamics in humans. , 1989, Stroke.

[16]  M. Siebler,et al.  Cerebral hemodynamics in obstructive sleep apnea. , 1993, Chest.

[17]  G. Bernardi,et al.  Impairment of daytime cerebrovascular reactivity in patients with obstructive sleep apnoea syndrome , 1998, Journal of sleep research.

[18]  P. Bath,et al.  Effect of antihypertensive agents on cerebral blood flow and flow velocity in acute ischaemic stroke: systematic review of controlled studies , 2008, Journal of hypertension.

[19]  B. Widder,et al.  Course of Carotid Artery Occlusions With Impaired Cerebrovascular Reactivity , 1992, Stroke.

[20]  V. Mohsenin,et al.  Gender differences in the expression of sleep-disordered breathing : role of upper airway dimensions. , 2001, Chest.

[21]  M. Poulin,et al.  Intermittent hypoxia and vascular function: implications for obstructive sleep apnoea , 2007, Experimental physiology.

[22]  C Caltagirone,et al.  Age and sex differences in cerebral hemodynamics: a transcranial Doppler study. , 1998, Stroke.

[23]  M. Poulin,et al.  Effects of continuous positive airway pressure on cerebral vascular response to hypoxia in patients with obstructive sleep apnea. , 2007, American journal of respiratory and critical care medicine.

[24]  M. Aldrich,et al.  Sleep-disordered breathing in patients with acute supra- and infratentorial strokes. A prospective study of 39 patients. , 1997, Stroke.

[25]  J. Bevan,et al.  Flow-induced constriction and dilation of cerebral resistance arteries. , 1990, Circulation research.

[26]  C Dodds.  Carbon dioxide and the cerebral circulation. , 1999, British journal of anaesthesia.

[27]  K. Franklin,et al.  Impairment of cerebral perfusion during obstructive sleep apneas. , 1994, American journal of respiratory and critical care medicine.

[28]  V. Somers,et al.  Microarray studies of genomic oxidative stress and cell cycle responses in obstructive sleep apnea. , 2007, Antioxidants & redox signaling.

[29]  C W Whitney,et al.  Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. , 2001, American journal of respiratory and critical care medicine.

[30]  D. Heistad,et al.  Regulation of the cerebral circulation: role of endothelium and potassium channels. , 1998, Physiological reviews.

[31]  T. Young,et al.  The occurrence of sleep-disordered breathing among middle-aged adults. , 1993, The New England journal of medicine.

[32]  V. Larrue,et al.  Dynamics of cerebral blood flow autoregulation in hypertensive patients , 2002, Journal of the Neurological Sciences.

[33]  D. Hillman,et al.  Association of sleep apnoea with myocardial infarction in men , 1990, The Lancet.

[34]  H. Freund,et al.  Cerebral blood flow velocity alterations during obstructive sleep apnea syndrome , 1990, Neurology.

[35]  C. Iadecola.  Neurovascular regulation in the normal brain and in Alzheimer's disease , 2004, Nature Reviews Neuroscience.

[36]  J. Hedner,et al.  Platelet function and fibrinolytic activity in hypertensive and normotensive sleep apnea patients. , 1995, Sleep.

[37]  B. Levine,et al.  Autonomic Neural Control of Dynamic Cerebral Autoregulation in Humans , 2002, Circulation.

[38]  C. Giller,et al.  Cerebral arterial diameters during changes in blood pressure and carbon dioxide during craniotomy. , 1993, Neurosurgery.

[39]  V. Somers,et al.  Impairment of Endothelium-Dependent Vasodilation of Resistance Vessels in Patients With Obstructive Sleep Apnea , 2000, Circulation.

[40]  P. Factor,et al.  Inflammation, Oxidative Stress, and Repair Capacity of the Vascular Endothelium in Obstructive Sleep Apnea , 2008, Circulation.

[41]  J. Concato,et al.  Obstructive sleep apnea as a risk factor for stroke and death. , 2005, The New England journal of medicine.

[42]  T. Young,et al.  Progression and regression of sleep-disordered breathing with changes in weight: the Sleep Heart Health Study. , 2005, Archives of internal medicine.

[43]  E. Rüther,et al.  Sleep apnea syndrome and cerebral hemodynamics. , 1996, Chest.

[44]  T. Young,et al.  Prospective study of the association between sleep-disordered breathing and hypertension. , 2000, The New England journal of medicine.

[45]  R. Aaslid,et al.  Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. , 1982, Journal of neurosurgery.

[46]  J. Stradling,et al.  Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials , 2004, Thorax.

[47]  Y. Gustafson,et al.  Obstructive sleep apnea is a risk factor for death in patients with stroke: a 10-year follow-up. , 2008, Archives of internal medicine.

[48]  P M Rossini,et al.  Outcome of carotid artery occlusion is predicted by cerebrovascular reactivity. , 1999, Stroke.

[49]  M. Nelson,et al.  Regulation of arterial diameter and wall [Ca2+] in cerebral arteries of rat by membrane potential and intravascular pressure , 1998, The Journal of physiology.

[50]  B K Rutt,et al.  MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis. , 2000, Stroke.

[51]  C. Iadecola,et al.  Glial regulation of the cerebral microvasculature , 2007, Nature Neuroscience.

[52]  Terry Young,et al.  Association of sleep-disordered breathing and the occurrence of stroke. , 2005, American journal of respiratory and critical care medicine.

[53]  T. Young,et al.  Clinical presentation of OSAS: gender does matter. , 2005, Sleep.