Κέντρο Υπέρτασης STRIDE-7 Γ Παθολογική Κλινική Πανεπιστημίου Αθηνών Νοσοκομείο Σωτηρία Υπέρταση και ΣΑΥ ΓΣ Στεργίου
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POSITION PAPER: Management of OSA and Hypertension Joint Recommendation European Society of Hypertension European Respiratory Society European COST members (COoperation in Scientific and Technological research) ACTION B26 on OSA Parati G, Lombardi C, Hedner J, Bonsignore MR, Grote L, Tkacova R, Levy P, Riha R, Bassetti C, Narkiewicz K, Mancia G, McNicholas WT, on behalf of the EU COST ACTION B26 members Journal of Hypertension 2012;30:633-646.
POSITION PAPER: Management of OSA and Hypertension OSA is now acknowledged in hypertension guidelines as a novel, frequent and modifiable cause of systemic resistant hypertension. Scientific data and clinical awareness about the interaction between OSA and hypertension continuously increasing. Increasing evidence that combined treatment, should be considered in patients with refractory hypertension and non-dipping profile. Journal of Hypertension 2012;30:633-646.
Hypertension and OSA Direct cause-effect association OSA effects on blood pressure OSA treatment effects on blood pressure Antihypertensive treatment in OSA induced hypertension
Prevalence of OSA in Hypertension New York Sleep Heart Health Study Jichi Medical University ABPM Study
OSA as a Risk Factor for Hypertension Toronto Sleep Clinic / Population study Lavie et al. Br Med J 2000; 320: 479-82 2,677 adults, 20-85 years Referred to Sleep Clinic with suspected OSA Apnoea: Significant predictor of systolic/diastolic BP (age, BMI, sex adjusted) BP - Hypertension prevalence Linearly increase ~ OSA severity (AHI)
OSA as a Risk Factor for Hypertension Toronto Sleep Clinic / Population study Lavie et al. Br Med J 2000; 320: 479-82 2,677 adults, 20-85 years Referred to Sleep Clinic with suspected OSA 1 additional apnoeic event/sleep hour 1% O.R. hypertension 10% decrease in Nocturnal O 2 saturation 13% O.R. hypertension
Prospective Study of the Association Between Sleep-Disordered Breathing and Hypertension Wisconsin Sleep Cohort Study Peppard et al. N Engl J Med 2000;342:1378-84. 709 participants 4 years of follow-up (184 follow-up with 8 years) Reference category: Baseline AHI of 0 events/hour AHI (events/hour) O.R. Hypertension 0.1 4.9 1.42 (95%CI 1.13-1.78) 5.0 14.9 2.03 (95%CI 1.29-3.17) 15.0 2.89 (95%CI 1.46-5.64)
OSA Hypertension
Apneic Asphyxia Peripheral Chemoreceptors Stimulation Sympathetic Nervous System Activation Cardiac Output Systemic Vascular Resistance Blood Pressure
Long-term chronic nightly episodic hypoxia and hypercapnia OSA (Pre-Apnea States) Marked repetitive changes in intrathoracic pressure Repetitive arousal and disrupted sleep architecture Sustained Night-time Elevation of Blood Pressure
Recurrent Elevation of NIGHT-TIME Blood Pressure Central or peripheral Resetting of Neural control mechanisms Resetting of the activity of circulating or bound vasoactive Hormones Sustained DAYTIME Hypertension Resetting of Vascular remodelling
HYPOXIA Chemoreceptors Sympathetic Nervous System Activation Vascular Wall Vasoactive Hormones Acutely Vasoconstriction Blood Pressure Chronically Smooth Muscle Hypertrophy Vascular Remodelling Sustained Hypertension
ATRIAL FIBRILLATION OSA Pathophysiological Mechanisms OSA Independent association with AF. Promotes AF initiation - Negative impact on treatment/recurrence. CPAP improves AF control. Zhang et al. Arrhythm Electrophys Rev. 2015; 4:14-18.
Night-time and Diastolic Hypertension are Common and Underestimated Conditions in Newly Diagnosed Apnoeic Patients Baguet, Mallion JM, Pepin JL. J Hypertens 2005;23:521-7 59 patients Referred for symptoms suggesting OSA BP considered as normal Office hypertension: Daytime hypertension: Nighttime hypertension: 42% 58% (all plus nighttime) 76% Most common hypertension: Diastolic or systolo-diastolic
Night-time and Diastolic Hypertension are Common and Underestimated Conditions in Newly Diagnosed Apnoeic Patients Baguet, Mallion JM, Pepin JL. J Hypertens 2005;23:521-7 Hypertension hugely underdiagnosed in OSA patients. Ambulatory BP monitoring detects twice as much hypertension than office measurements.
Nocturnal BP Dipping Profiles Kario et al. Hypertension 2001;38:852-7. mmhg 200 150 Systolic BP Extreme-dippers Dippers Non-dippers Risers 100 Diastolic BP 50 0 Sleep 10 12 14 16 18 20 22 0 2 4 6 8 10 Hour
Prognostic Significance of the Nocturnal BP fall Syst-Eur Study Staessen et al. JAMA 1999;282:539-46.
Mr EA, 44 y, Rx (-) 24-h 118/77 75 Day 126/84 78 Night 99/61 69 66 (83%)
67 (90%) Mrs EK, 62 y Rx (3) Office 146/82 24-h 123/76 71 Day 118/75 76 Night 132/81 61
mmhg Can Home BP Monitoring in Assessing Nocturnal BP and Detecting of Non-Dippers? Stergiou GS, et al. Am J Hypertens 2012;25:974-8. Agreement in detecting non-dippers Δ=1.6±5.1 P=0.04 74% N=81
Association of AHI with diastolic blood pressure (r) v OFFICE HOME DAY NIGHT Destounis A, Cholidou K, Kollias A, Karpettas N, Markozannes E, Alchanatis E, Stergiou GS. Hypertension Center, Third University Department of Medicine, First University Department of Respiratory Medicine, Sotiria Hospital, Athens, Greece.
Asleep Home Blood Pressure in OSA Stergiou GS, Triantafyllidou E, Cholidou K, Kollias A, Destounis A, Nasothimiou EG, Markozannes E, Alchanatis M. Blood Press Monit 2013;18:21-6.
Phenotypes of Hypertension in OSA Resistant hypertension Masked hypertension Nocturnal hypertension (non-dipper-riser pattern, midnight BP surge) Morning hypertension (exaggerated morning BP surge) Hypertension with increased heart rate Diastolic hypertension (predominant) in younger
Drug-Resistant Hypertension: High prevalence of Unrecognized OSA Logan et al. J Hypertens 2001;19:2271-7. Drug-Resistant Hypertension (N=41) Clinic BP >140/90 mmhg Sensible combination of 3+ antihypertensive drugs Maximally recommended doses Extraordinarily high OSA prevalence 83% Potential role of OSA in pathogenesis of drug-resistant hypertension
? 2003
CPAP Effect on Blood Pressure
Hu et al. J Clin Hypertens 2015;17:215-23. Effect of CPAP on 24h ABPM Meta-Analysis of 7 RCTs SYST BP SBP 2.3 DBP 2.0 mmhg DIAST BP Nighttime BP
Effect of OSA Correction on BP in Untreated Hypertension Hla et al. Chest 2002;122:1125-32 24 untreated hypertensives, 30-60 ys 14 OSA - 10 non OSA 3 weeks CPAP BP Change with CPAP (age, BMI adjusted) NOCTURNAL DAYTIME Non OSA: +0.3 / -0.7 mmhg +0.4 / -1.7 mmhg (NS) (NS) OSA group: -7.8 / -5.3 mmhg -2.7 / -2.3 mmhg (p 0.02/0.03) (NS) Nocturnal hypertension causally related to AH events
CPAP in OSA and Resistant Hypertension Meta-Analysis of 5 RCTs 0 Systolic BP Diastolic BP -1-2 -1,9 * -1,5-3 -3,2 * -3-2,5-4 -5 * -4,5 24 hour Daytime Nighttime Liu et al. J Clin Hypertens 2016;18:153-9.
CPAP Usage and Change in Blood Pressure (Meta-analysis of CPAP trials) Bazzano et al. Hypertension 2007;50:417-23.
CPAP in OSA with Resistant Hypertension: Randomized Controlled Trial 3 months Lozano L, et al. J Hypertens 2010;28:2161-8.
Refractory Hypertension and OSA: Acute and Chronic effects of CPAP on BP Logan et al. Eur Respir J 2003; 21: 241-7. 11 refractory hypertensive OSA patients Single Night CPAP OSA abolished Nocturnal systolic BP: 6.0 mmhg Nocturnal diastolic BP: 5.0 mmhg Two Months CPAP Nocturnal systolic BP: 14.4 mmhg Nocturnal diastolic BP: 7.8 mmhg Daytime systolic BP: 9.3 mmhg 24-hour systolic BP: 11.0 mmhg Acute abolition of OSA by CPAP reduces Nocturnal BP Chronically also reduces Daytime BP
Hu et al. J Clin Hypertens 2015; 17:215-23. Effect of CPAP on 24h ABPM Meta-Analysis of 7 RCTs
CPAP BP Effects in OSA (RCTs) BP STATUS Normotension [2 tr] Pre-HTN / Masked [1 tr] Controlled HTN [3 tr] Uncontrolled HTN ± Resistant [4 tr] EFFECT No or very mild Mild No or modest Modest 2 mmhg COMMENT Neutral or minimal effect expected 1 small trial in severe OSA SBP 5 mmhg, Pre-/Masked HTN frequency Variable results. Suboptimal CPAP in some studies Variable results (0-8 mmhg) More evident in sleepy patients Suboptimal CPAP in some studies Resistant HTN [6 tr] Mild 3 5 mmhg Fatureto-Borges F, et al. Integr Blood Press Control 2016:9 43-7. Negative 1/6 studies. Variable results (0-10 mmhg). Low proportion of controlled patients Dependent on CPAP adherence
CPAP effects on Muscle SNS Activity and MRI SNS Brainstem Activity Henderson et al. Front Neurosci 2016;20:1-11. CPAP IN OSA: RESTORING EFFECTS ON BRAINSTEM STRUCTURE AND FUNCTION
Effect of CPAP on Arterial Stiffness in OSA with Hypertension META-ANALYSIS 3 studies (2 observational, 1 RCT) N=186 Statistically significant decrease in arterial stiffness SMD = -0.65 95% C.I. -1.14 to -0.16 z = 2.60, P <0.01 Lin et al. Eur Arch Otorhinolaryngol 2016, Feb 9, Epub.
OSA Choice of Antihypertensive Drugs
Choice of Antihypertensive Drugs in OSA Effect of drugs on: Sleep Sleep apnea activity Blood pressure in OSA patients
Effect of Antihypertensive Drugs On Sleep Drug Effect on Sleep Clonidine Guanabenz Methyldopa Reserpine REM-Sleep-suppression NREM (2 and 3/4)-increase Prolonged rem-sleep Shortened nrem 3/4-sleep REM-sleep -increase Reduced sleep latency Daytime sleepiness increase Sleep time prolongation Increase in daytime sleepiness Attention deficits Increased daytime sleepiness Prazosine Increased daytime sleepiness REM-Sleep modification? β-receptor- Blocker Increased daytime sleepiness Dream content/nightmares Increased nocturnal awakening REM-sleep suppression? Increased time awake during sleep period (eeg ) Melatonin-suppression ACE-Inhibitors No major changes in sleep eeg Ca-Antagonist No major changes in sleep eeg Cough may cause arousal from sleep Pharmacokinetic changes in sedative drugs? Diuretics No major changes in sleep eeg Nocturia cause sleep complaints
Atihypertensive Drug Treatment in OSA Kraiczi et al. Am J Respir Crit Care Med 2000;161:1423-8. ** * Treatment: 6 wk 1. Atenolol (50 mg) 2. Amlodipine (5 mg) 3. Enalapril (20 mg) 4. Hydrochlorothiazide (25 mg) 5. Losartan (50 mg) 40 randomized patients (crossover) 2 of 5 agents for each - 3 weeks washout
Atihypertensive Drugs in OSA BP OSA Beta-Blocker ++?? -?? Dihydropyridine +? +? ACE Inhibitor +? +? Angio Blocker +? +/-? Aldo Antagonist? +? Diuretic +? +? Nocturnal Rx????
Bedtime Barnidipine in Non-Dipper Hypertensives with OSA not on CPAP Δ = 9 mmhg Δ = 18 mmhg Δ = 5 mmhg Δ = 9 mmhg N=41, Uncontrolled Crippa et al. Eur Rev Med Pharmacol Sci 2016;20:339-44.
Effects of Antihypertensive Drugs in OSA Not uniform. Few studies compared different agents in parallel or crossover design. Statistical power usually poor due to small patient numbers. No drug class reproducibly shown to be more efficacious. Guidelines do not provide recommendation due to limited data from prospective trials. Additional research needed. Parati G, et al. J Hypertens 2012;30:633-46.
Hypertension and OSA Direct cause-effect association OSA effects on blood pressure *** *** OSA treatment effects on blood pressure Antihypertensive treatment in OSA induced hypertension * **
Κέντρο Υπέρτασης STRIDE-7 Γ Παθολογική Κλινική Πανεπιστημίου Αθηνών Νοσοκομείο Σωτηρία Υπέρταση και ΣΑΥ ΓΣ Στεργίου