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Sindrome delle apnee notturne e ipertensione arteriosa

Sindrome delle apnee notturne e ipertensione arteriosa. M. Scoppio Responsabile reparto di Nefrologia Ambulatorio ipertensione arteriosa Ospedale San Camillo-Forlanini. 26 maggio 2007. Sleep apnea and hypertension. Il 96% degli uomini e il 65% delle donne con

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Sindrome delle apnee notturne e ipertensione arteriosa

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  1. Sindrome delle apnee notturne e ipertensione arteriosa M. Scoppio Responsabile reparto di Nefrologia Ambulatorio ipertensione arteriosa Ospedale San Camillo-Forlanini 26 maggio 2007

  2. Sleep apnea and hypertension • Il 96% degli uomini e il 65% delle donne con • “ipertensione resistente” hanno OSA • Gli ipertesi resitenti con OSA hanno livelli più alti • di aldosterone plasmatico e incidenza più elevata • di aldosteronismo primario, rispetto agli ipertesi • resistenti senza OSA OSA E IPERTENSIONE RESISTENTE

  3. Sleep Apnea and Potential Health Risks Excessive sleepiness Neurocognitive deficits Crashes (motorcar accidents) Sleep Apnea Hypertension Cardiovasculare disease (IMA,stroke,SCA,CHF) Insulin-resistance

  4. Prevalence of OSA In Patients with Cardiovascular and Cerebrovascular Disease 50% ------------ Hypertension 25% ----------- Congestive Cardiac Failure OSA 60% -------- Stroke 30% --------- Acute Coronary Syndrome Lattimore Jl JACC 2003;41

  5. OSA Morbo di Alzheimer Link genetico APOE ε4 two recent reports have found increased OSA in subjects with APOE ε4, a genetic factor associated with Alzheimer’s disease. The association of APOE ε4 with OSA has been suggested to be mediated by damage to the CNS and resulting abnormal regulation breathing during sleep Am J Respir Crit Care Med Vol 170. pp 1349–1353, 2007

  6. Obstructive sleep apnea and risk for hypertension Peppard PE. N Engl J Med. 2000; 342:1378-84

  7. EVIDENCE ON THE ASSOCIATION BETWEEN OSA AND HYPERTENSION:Recent Human Studies • General population epidemiology studies • Clinic based epidemiology studies • Case control studies • Intervention studies

  8. EVIDENCE ON THE ASSOCIATION BETWEEN OSA AND HYPERTENSION:Recent Human Studies Studio trasversale Studio longitudinale

  9. 2/3 paz. con OSA OBESI ½ paz. ipertesi OSA LINK 2/3 paz. obesi IPERTENSIONE

  10. Meslier et al 2003 595 male patients referred for polysomnography underwent a 2 hour oral glucose tolerance test. 494 pts had OSAS (AHI > 10) Fasting and postload blood glucose increased with severity of sleep apnea Insulin sensitivity decreased with increasing severity of sleep apnea BMI, age and AHI are all have an independent effect on blood glucose and insulin sensitivity Ip et al 2002 185 pts with OSAS (AHI>5) Insulin resistance increased with age obesity (main determinant) Independent determinants of OSA were AHI and min 02 sat Punjabi et al 2003 [Review] Habitual snoring is associated with abnormal fasting glucose and insulin values independent of age and BMI Prospective data from two separate studies indicate that habitual snoring is associated with more than a 2-fold risk of developing DM type II over a ten year period independent of BMI and other confounders Several studies have suggested that the minimum oxygen saturation and AHI are predictive of glucose intolerance and insulin resistance independent of BMI, age and waist to hip ratio OSA and Impaired Glucose Metabolism

  11. Sindrome Metabolica: Definizione Cluster di fattori di rischio emodinamici e metabolici tradizionali e non tradizionali (emergenti), che associati aumentano il rischio didiabete tipo 2e dieventi cardiovascolari Danno logaritmico

  12. Definition of metabolic syndrome Central obesity Men >102 cm Women >88 cm TG ≥150 mg/dL HDL cholesterol Men <40 mg/dL Women <50 mg/dL Blood pressure ≥130/≥85mmHg Fasting glucose ≥110 mg/dL Three or more of the following five risk factors: Waist circumference

  13. Male Female 35 No. of deaths(left axis) 30 25 % of all deaths(right axis) 20 Number of deaths (thousands) % All deaths (male + female) 15 10 5 0 Despite therapeutic advances, cardiovascular disease remains the leading cause of death Data for 2002 National Center for Health Statistics 2004

  14. HDL-C TNF IL-6 Insulin AbdominalObesity Glu TG PAI-1 Unmet clinical needs to address in the next decade Major Unmet Clinical Need Novel Risk Factors Classical Risk Factors Metabolic syndrome  LDL-C  BP Smoking T2DM CARDIOVASCULAR DISEASE

  15. “TWIN EPIDEMICS” DIABETE TIPO 2 OBESITA’ DIABESITY GLOBESITY IPERTENSIONE ARTERIOSA MALATTIE CARDIO-VASCOLARI

  16. Childhood Obesity, Inflammation, and Apnea What Is the Future for Our Children? numerous recent studies have demonstrated the presence of hypertension and increased inflammation in children with OSAS AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 171 2005

  17. OSA e SINDROME METABOLICA Ipertensione Obesità Insulino-resistenza Dislipidemia aterogena OSA NEFROPATIA URATICA PCOS NASH L’OSA ha probabilità 9 volte superiore di sviluppare sindrome metabolica rispetto alla popolazione di controllo

  18. Obesità (sindrome metabolica) OSA ?

  19. Valutazione del sovrappeso e dell’obesità • Indice di massa corporea:Peso (kg)/altezza(m2) • Circonferenza addominale • Rischio elevato: • Uomini > 102 cm • Donne > 88 cm GRASSO VISCERALE The Practical Guide Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. NIH Publication, October 2000 NIH Pub No 00-4084

  20. Effetti cardiometabolici sfavorevoli dei prodotti degli adipociti ↑ Lipoprotein lipasi Ipertensione ↑ Angiotensinogeno ↑ IL-6 Infiammazione Dislipidemia aterogenica ↑ Insulina ↑ FFA Adiposetissue ↑ TNFα ↑ Resistina ↑ Leptina ↑ Adipsina(Complemento D) ↑ Lactato Diabete tipo 2 ↑ Inibitore dell’attivatore del plasminogeno-1(PAI-1) ↓ Adiponectina Aterosclerosi Trombosi Lyon 2003; Trayhurn et al 2004; Eckel et al 2005

  21. Sindrome Metabolica e OSA OSA Insulino resistenza ipossiemia - ipercapnia Ag II ROS (radicali liberi) Ipertono simpatico Eventi cardiovascolari Ipertensione arteriosa

  22. IPERTONO SIMPATICO renale

  23. Profilo pressorio caratteristico dell’OSA • Ipertensione arteriosa diastolica Ipertensione clinica • Ritmo circadiano di tipo non-dipper • Eccessivo rialzo pressorio al risveglio • Alta variabilità pressoria (DS) • Ipertensione secondaria e resistente

  24. UTILITA’ dell’ABPM

  25. Rilevanza clinica dei fenomeni pressori nelle 24 ore Danno d’organo Pressione notturna più alta Minore  giorno/notte Eccessivo aumento pressorio mattutino Aumento della variabilità pressoria Picchi pressori eccessivi/ numerosi Rischio cardiovascolare Progressione a nefropatia diabetica Associazione con un picco mattutino degli eventi cardiovascolari

  26. Analisi di Kaplan-Meier per gli eventi cardiovascolari fatali e non fatali in pazienti con variabilitàpressoria aumentata (> 15 mmHg) o normale (< 15 mmHg) Variabilità ≤ 15 Variabilità > 15 Sander D. et al, Circulation 2000; 102: 1536-1541

  27. Variabilità della pressione sistolica come fattore di rischio per ictus e mortalità cardiovascolare negli ipertesi anziani Rischio di ictus a 2 anni Variabilità notturna della PAS PAS notturna (mmHg) Journal of Hypertension 2003; 21: 1-7

  28. OSA e IPERTENSIONE ARTERIOSA Monitoraggio ambulatorio della PA 24 ore e rialzo pressorio al risveglio (morning surge pressure)

  29. Mortalità nelle prime tre ore dopo il risveglio 25 20 Numero di morti 10 0 sonno 0-3 3-6 6-9 9-12 12-15 Ore dopo il risveglio Willich. Am J Cardiol 1992; 70: 65-68

  30. Variazioni circadiane nell’incidenza di morte cardiaca improvvisa - Framingham Heart Study Ore del giorno Willich. Am J Cardiol 1987; 60: 801-806

  31. Sudden cardiac death and OSA Gami, A. S. et al. N Engl J Med 2005;352:1206-1214

  32. Picchi temporalidei ritmi circadiani umani h 24 Cortisolo RAS AgII Aldosterone Catecolamine Adesività piastrinica Viscosità ematica PA h 6 h 18 FC h 12 NO Fibrinolisi

  33. OSA e EPO

  34. Elevated Levels of C-Reactive Protein and Interleukin-6 in Patients With Obstructive Sleep Apnea Syndrome Are Decreased by Nasal Continuous Positive Airway Pressure early clinical signs of atherosclerosis ! Circulation. 2003;107

  35. Incidence of sleep-related disorders in 440 consecutive patients with HF Lamp B. Heart Failure Society of America 2004 Annual Scientific Meeting; September 12-15, 2004; Toronto

  36. SO2 e Massa Ventricolare sinistra Data supporting a possible cause and effect relationship between OSA and LVH. 6 months of nocturnal CPAP to patients with severe OSA was associated with a significant reduction in LV wall thickness. Chest 2003;124 Hypertension 2007;49:34-39

  37. Correlazione tra AHI e SS e GC JACC Vol. 47, No. 7, 2006

  38. Effetto della CPAP su SS e GC JACC Vol. 47, No. 7, 2006

  39. Nocturnal Ischemic Events in Patients With Obstructive Sleep Apnea Syndrome. Effects of Continuous Positive Air Pressure Treatment. CPAP 10/51 paz. con OSA J Am Coll Cardiol 1999;34

  40. OSA treatment in CAD Milleron et al Eur Heart J 2004

  41. Treatment of heart failure • Once confirmed LV dysfunction on echo (not symptoms alone), treatment is a formula: • Diuretics • Spironolactone • ACE inhibitor/ARBs • Beta blocker • And now CPAP • Drug therapy alone does not decrease severity of sleep apnea in heart failure

  42. Arrhythmias associated with SDB • The following have been associated with SDB: • Classically severe bradycardia (sinus arrest, AV block) • Atrial and ventricular ectopics • SVT, Atrial flutter, AF • Sustained and nonsustained VT • Causality is not proven but tend to occur most with severe OSA and hypoxia

  43. OSA e FA Gami AS Circulation 2004;110:364-7

  44. Recurrence of AF 12 months after cardioversion Kanagala R Circulation 2003;107:2589-94

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