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Diapositiva 1 - lista ippocrate
Sindrome delle apnee notturne e ipertensione arteriosa 26 maggio 2007 M. Scoppio Responsabile reparto di Nefrologia Ambulatorio ipertensione arteriosa Ospedale San Camillo-Forlanini 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 Sleep Apnea and Potential Health Risks Excessive sleepiness Neurocognitive deficits Crashes (motorcar accidents) Hypertension Sleep Apnea Cardiovasculare disease (IMA,stroke,SCA,CHF) Insulin-resistance Prevalence of OSA In Patients with Cardiovascular and Cerebrovascular Disease 25% ----------Congestive Cardiac Failure 50% -----------Hypertension OSA 30% --------Acute Coronary Syndrome 60% -------Stroke Lattimore Jl JACC 2003;41 Morbo di Alzheimer OSA 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 Obstructive sleep apnea and risk for hypertension Peppard PE. N Engl J Med. 2000; 342:1378-84 EVIDENCE ON THE ASSOCIATION BETWEEN OSA AND HYPERTENSION: Recent Human Studies • • • • General population epidemiology studies Clinic based epidemiology studies Case control studies Intervention studies EVIDENCE ON THE ASSOCIATION BETWEEN OSA AND HYPERTENSION: Recent Human Studies Studio trasversale Studio longitudinale 2/3 paz. con OSA ½ paz. ipertesi OBESI OSA LINK 2/3 paz. obesi IPERTENSIONE OSA and Impaired Glucose Metabolism • • • • • • • • • 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 Cluster di fattori di rischio emodinamici e metabolici tradizionali e non tradizionali (emergenti), che associati aumentano il rischio di diabete tipo 2 e di eventi cardiovascolari 6 eventi CV/100 paz./anno 5,27 5 RR 4 3,35 2,97 Danno logaritmico 3 1,96 2 1,54 1 0 1 2 3 4 n°fattori di rischio 5 Definition of metabolic syndrome Three or more of the following five risk factors: Central obesity Men Women Waist circumference >102 cm >88 cm TG ≥150 mg/dL HDL cholesterol Men Women <40 mg/dL <50 mg/dL Blood pressure ≥130/≥85mmHg Fasting glucose ≥110 mg/dL 500 No. of deaths (left axis) 400 300 Male Female % of all deaths (right axis) 200 100 0 35 30 25 20 15 10 5 0 Heart disease and stroke Cancer Accidents Data for 2002 National Center for Health Statistics 2004 Chronic lower resp. disease Diabetes % All deaths (male + female) Number of deaths (thousands) Despite therapeutic advances, cardiovascular disease remains the leading cause of death Unmet clinical needs to address in the next decade Major Unmet Clinical Need Classical Risk Factors Novel Risk Factors Metabolic syndrome HDL-C LDL-C BP TNF IL-6 Insulin Abdominal Smoking Obesity Glu TG PAI-1 CARDIOVASCULAR DISEASE T2DM “TWIN EPIDEMICS” OBESITA’ DIABETE TIPO 2 GLOBESITY DIABESITY IPERTENSIONE ARTERIOSA MALATTIE CARDIO-VASCOLARI 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 OSA e SINDROME METABOLICA Ipertensione Insulino-resistenza Obesità Dislipidemia aterogena OSA NEFROPATIA URATICA PCOS NASH L’OSA ha probabilità 9 volte superiore di sviluppare sindrome metabolica rispetto alla popolazione di controllo Obesità (sindrome metabolica) OSA ? 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 Effetti cardiometabolici sfavorevoli dei prodotti degli adipociti ↑ Lipoprotein lipasi Infiammazione ↑ Angiotensinogeno ↑ IL-6 ↑ TNFα ↑ Insulina Adipose tissue ↑ Adipsina (Complemento D) ↓ Adiponectina Aterosclerosi Ipertensione ↑ FFA Dislipidemia aterogenica ↑ Resistina ↑ Leptina ↑ Lactato ↑ Inibitore dell’attivatore del plasminogeno-1 (PAI-1) Diabete tipo 2 Trombosi Lyon 2003; Trayhurn et al 2004; Eckel et al 2005 Sindrome Metabolica e OSA Insulino resistenza OSA ipossiemia - ipercapnia ROS (radicali liberi) Ag II Ipertono simpatico Eventi cardiovascolari Ipertensione arteriosa IPERTONO SIMPATICO renale 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 UTILITA’ dell’ABPM Rilevanza clinica dei fenomeni pressori nelle 24 ore Pressione notturna più alta Minore giorno/notte Eccessivo aumento pressorio mattutino Aumento della variabilità pressoria Picchi pressori eccessivi/ numerosi Danno d’organo Rischio cardiovascolare Progressione a nefropatia diabetica Associazione con un picco mattutino degli eventi cardiovascolari Analisi di Kaplan-Meier per gli eventi cardiovascolari fatali e non fatali in pazienti con variabilità pressoria aumentata (> 15 mmHg) o normale (< 15 mmHg) Liberi da eventi cardiovascolari 1,00 0,95 0,90 Variabilità ≤ 15 Variabilità > 15 0,85 0,80 0 20 40 60 80 100 120 140 160 Settimane Sander D. et al, Circulation 2000; 102: 1536-1541 Variabilità della pressione sistolica come fattore di rischio per ictus e mortalità cardiovascolare negli ipertesi anziani Rischio di ictus a 2 anni 0,15 0,1 0,05 31 24 0 17 190 157 10 123 90 3 Journal of Hypertension 2003; 21: 1-7 OSA e IPERTENSIONE ARTERIOSA Monitoraggio ambulatorio della PA 24 ore e rialzo pressorio al risveglio (morning surge pressure) Mortalità nelle prime tre ore dopo il risveglio 25 Numero di morti 20 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 Variazioni circadiane nell’incidenza di morte cardiaca improvvisa - Framingham Heart Study 25 Numero di morti 20 15 10 5 0 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Ore del giorno Willich. Am J Cardiol 1987; 60: 801-806 Sudden cardiac death and OSA Gami, A. S. et al. N Engl J Med 2005;352:1206-1214 Picchi temporali dei ritmi circadiani umani h 24 PA h 18 FC h 12 h6 Cortisolo RAS AgII Aldosterone Catecolamine Adesività piastrinica Viscosità ematica NO Fibrinolisi OSA e EPO 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 Incidence of sleep-related disorders in 440 consecutive patients with HF Sleep-related disorder Incidence (%) Central sleep apnea Obstructive sleep apnea 25 28 Milder sleep-related disorders No sleep-related disorder 18 29 Lamp B. Heart Failure Society of America 2004 Annual Scientific Meeting; September 12-15, 2004; Toronto 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 Correlazione tra AHI e SS e GC JACC Vol. 47, No. 7, 2006 Effetto della CPAP su SS e GC JACC Vol. 47, No. 7, 2006 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 OSA treatment in CAD Milleron et al Eur Heart J 2004 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 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 OSA e FA Gami AS Circulation 2004;110:364-7 Recurrence of AF 12 months after cardioversion Kanagala R Circulation 2003;107:2589-94 Prevalence of OSA after stroke Good Harbison Parra Dyken Harbison Bassetti Wessendorf >40% Parr a Davies Wolk et al. Hypertension, 2003; 42 TERAPIA ANTIPERTENSIVA SINDROME METABOLICA PROTEZIONE METABOLICA CONTROLLO PRESSORIO PROTEZIONE D’ORGANO Terapia antipertensiva nella Sindrome Metabolica Farmaci che riducono la pressione arteriosa e che migliorano il quadro metabolico BLOCCANTI IL SRA ACE-inibitori Sartani Potenziale influenza di telmisartan sui recettori PPAR e sull’Angiotensina II + SARTANI PPAR Insulino resistenza Dislipidemia – Angiotensina II Flogosi cellulare Proliferazione cellulare Ipertensione Stress ossidativo Aterosclerosi Kurtz TW et al. J Hyperten 2004; 22: 2253-2261 ANTIALDOSTERONICI treatment of aldosterone excess induces not only the improvement of the cardiac alterations, but also of the metabolic complications related to hyperaldosteronism Journal of Hypertension 2007, 25:177–186 2003 European Society of Hypertension - European Society of Cardiology guidelines for the management of arterial hypertension Diuretics ß-blockers AT1-receptor blockers 1-blockers Calcium antagonists ACE inhibitors Ten Years Ago - April 1993! SLEEP APNEA – A MAJOR PUBLIC HEALTH PROBLEM EDITORIAL • “Among specific sleep disorders, the most serious in terms of morbidity and mortality is obstructive sleep apnea.” • “... it is time for the nation to wake up to the staggering impact of sleep disturbances on the health and welfare of our society, an impact that rivals that of smoking.” M. Scoppio