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2	Outlines of presentation Brief History of Sleep apnea Epidemiology: From an exotic disease to a prevalent syndrome Sleep apnea is associated with HT, what are the evidence? Oxidative stress – the culprit of sleep apnea Endothelial dysfunction, a prelude to CVD Aborting the process
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7	The first documented apneas
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16	Outlines of presentation Epidemiology: From an exotic disease to a prevalent syndrome Sleep apnea is associated with HT, what are the evidence? Oxidative stress – the culprit of sleep apnea Endothelial dysfunction, a prelude to CVD Aborting the process
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21	Young’s et al NEJM study
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23	Outlines of presentation Epidemiology: From an exotic disease to a prevalent syndrome Sleep apnea is associated with HT, what are the evidence? Oxidative stress – the culprit of sleep apnea Endothelial dysfunction, a prelude to CVD Aborting the process
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28	Total number of subjects 11,157 Feb/00 Lavie, Herer and Hoffstein, BMJ. Sleep lab population, 2677 patients, OR AHI=30 vs. AHI<10 ~1.33 April/00 Nieto et al, JAMA Sleep-Heart Health Study, 6132 subjects, AHI>30 vs.<1.5 OR=1.37 May/00 Peppard et al, N Engl J Med Wisconsin Sleep Study, prospective, 709 subjects followed for 4 yrs, OR AHI>15 vs. 0=2.89 Aug/00 Bixler et al, Arch Intern Med. 1741 subjects, SDB independently associated with HT, strongest in young June/00 Grote, Hedner and Peter, J. Hypertension, 599 patients, RDI independent predictor in pat <50 y
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35	More supporting evidence Prospective studies Peppered et al. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000 Treatment effects Pepperell et al. Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomized parallel trial. Lancet. 2002 Animal model Brooks et al. Obstructive sleep apnea as a cause of systemic hypertension. Evidence from a canine model. J. Clin Invest 1997.
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40	Outlines of presentation Epidemiology: From an exotic disease to a prevalent syndrome Sleep apnea is associated with CVD, what are the evidence? Oxidative stress – the culprit of sleep apnea Endothelial dysfunction, a prelude to CVD Aborting the process
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44	Increased Oxidative stress in OSA Production of free radicals from Monocytes, lymphocytes and granulocytes Pro-inflammatory cytokines Anti-inflammatory cytokines Adhesion molecules Oxidized plasma Lipids Diminished antioxidants capacity (Decreased PON1, increased 2-2 Hp phenotype)
45	Basal and PMA DHE oxidation in controls and OSA patients matched by age sex and BMI
46	Basal and PMA DHE oxidation in controls and OSA patients matched by age sex and BMI
47	Basal and PMA DHE oxidation in controls and OSA patients matched by age sex and BMI
48	Increased Oxidative stress in OSA Production of free radicals from Monocytes, lymphocytes and granulocytes Pro-inflammatory cytokines Anti-inflammatory cytokines Adhesion molecules Oxidized plasma Lipids Diminished antioxidants capacity (Decreased PON1, increased 2-2 Hp phenotype)
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50	TBARS and Peroxides concentrations in OSA patients with and without CAD
51	PON1 activity in OSA adjusted for age, BMI, hypercholesterolemia, creatinine and glucose
52	Oxidative stress in Sleep Apnea
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55	Outlines of presentation Epidemiology: From an exotic disease to a prevalent syndrome Sleep apnea is associated with CVD, what are the evidence? Oxidative stress – the culprit of sleep apnea Endothelial dysfunction, a prelude to CVD Aborting the process
56	"shear stress and changes in..." shear stress and changes in hydrostatic pressure are sensed by the endothelium and stimulate nitric oxide release resulting in reactive hyperemia and vasodilation
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59	PAT-Reactive Hyperemia Protocol
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65	Early signs of atherosclerosis in sleep apnea Increased intima-media thickness Drager et al, 2005 Arterial plaque formation Kaynak et al, 2003 Calcified artery atheromas Friedlander et al, 1999 Atherosclerotic lesions Aboyans et al, 1999 Higher pulse wave velocity Drager et al, 2005
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67	Progression from ED to CVD (2)
68	Outlines of presentation Epidemiology: From an exotic disease to a prevalent syndrome Sleep apnea is associated with CVD, what are the evidence? Oxidative stress – the culprit of sleep apnea Endothelial dysfunction, a prelude to CVD Aborting the process
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70	Mean EF significantly improved following 3 months CPAP treatment
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74	Population 14,984 male adult patients studied in the Technion Sleep Medicine Center during a 9-year period (January 1^st, 1991- October 1^st , 2000) because of suspected OSA Examination age: 48.4±12.3 yrs Prior to September 1^st, 2001, 2.6% (481) of the men died Death age: 62.4±12.1 Follow-up period: 4.8 years
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