blood pressure Untreated hypertension Nocturnal hypertension Resistant hypertension OSA FACTOR Severe OSAS AHI by yX8bo4nG

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 Κέντρο Υπέρτασης, Γ’ Παθολογική Κλινική
Πανεπιστημίου Αθηνών, Νοσοκομείο Σωτηρία
Obstructive Sleep Apnea
   and Hypertension

    Direct cause-effect association.
    OSA effects on blood pressure.
    CPAP 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
 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 O2 saturation
      ↑13% O.R. hypertension
   Sleep Heart Health Study
            Nieto et al, Pickering TG. JAMA 2000;283:1829-36

             6132 subjects, Population-based
                >40 years - 53% women


      AHI Category                         Sleep Time (%)
   Highest (≥30/h) versus                  < 90% O2 Saturation
       Lowest (<1.5/h)                      (≥12% vs <0.05%)

       Hypertension                             Hypertension
        RR 1.37                                  RR 1.46
     (95%CI 1.03-1.83)                      (95% CI 1.12-1.88)
         P=0.005                                P<0.001

Both sexes, old/young, ethnic groups, normal/overweight
Adjustment: BMI, neck circ, W/H ratio, alcohol, smoking
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)
    Sleep Apnea and Hypertension
              Hla et al. Ann Intern Med 1994;120:382-8.

          Wisconsin Sleep Cohort Study
           147 men and women, 30-60 years


Higher BP in OSA subjects
(p<0.05)                                    Day-BP        Night-BP
   No apneas or hypopneas                   122/75        104/62
   ≥5 apneas /hypopneas/h sleep             131/80        113/66

OSA/Hypertension:
Dose dependent association
  5 apneic or hypopneic episodes/h sleep              OR 2.0
  25 apneic or hypopneic episodes                     OR 5.0

Adjusted for obesity, age, and sex
     Apneic Asphyxia
                   
     Peripheral Chemoreceptors
            Stimulation
                   
             Sympathetic
            Nervous System
              Activation


 Cardiac               Systemic Vascular
  Output                    Resistance



             Blood Pressure
             Long-term chronic nightly episodic
             hypoxia and hypercapnia

OSA          Marked repetitive changes in
(Pre-Apnea   intrathoracic pressure
 States)
             Repetitive arousal and disrupted
             sleep architecture

                                       

             Sustained Night-time
             Elevation of Blood Pressure
               Central or peripheral
               resetting of neural
Recurrent      control mechanisms
Elevation of
                                           Sustained
NIGHT-TIME     Resetting of the activity   DAYTIME
Blood          of circulating or bound     Hypertension
Pressure       vasoactive hormones


               Resetting of vascular
               remodelling
                   HYPOXIA
                        
                Chemoreceptors
                        
          Sympathetic Nervous System
                  Activation
                        
                 Vascular Wall
              Vasoactive Hormones

   Acutely                         Chronically
                                         
Vasoconstriction                  Smooth Muscle
                                   Hypertrophy
     Blood                               
   Pressure                     Vascular Remodelling

              Sustained Hypertension
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
             and BP “considered” as normal

       Office hypertension:        42%

     Daytime hypertension:         58% (all plus nighttime)

   Nighttime hypertension:         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.
Αξιολόγηση Αρτηριακής πίεσης




                    Ιατρείο
Αξιολόγηση Αρτηριακής πίεσης




            24ωρη Αρτ Πίεση
Nocturnal BP Dipping Profiles
                 Kario et al. Hypertension 2001;38:852-7.

                                                              Extreme-dippers
                                                              Dippers
mmHg
 200                                                          Non-dippers
       Systolic BP                                            Risers

 150


 100
       Diastolic BP


  50

                                          Sleep
   0


       10   12   14   16   18   20   22   0   2   4   6   8   10   Hour
  Dipping Pattern and Stroke
        Probability of stroke-free   1.0



                                     0.9

                                               p<0.0001
                                     0.8


                                               Extreme dippers
                                     0.7       Dippers
                                               Non-dippers
                                               Risers
                                     0.6
                                           0   10     20     30   40   50   60   70

                                                     Follow-up (months)
Kario et al. Hypertens 2001;38:852
        Prognostic
Significance of the
         Nocturnal
            BP fall
                 Syst-Eur
                   Study




                Staessen et al.
          JAMA 1999;282:539-46.
Morning Hypertension & Diurnal BP Variation




Kario K. Hypertens Res 2009;32:428-32.
Mr EA, 44 y, Rx (-)   24-h 118/77 75
                      Day 126/84 78
                      Night 99/61 69




                           66 (83%)
Mr ND, 76 y, Rx (1)     24-h 144/76 87
                        Day 153/81 88
Office BP 174/82        Night 124/63 84




               156/84   116/57

                                 72 (94%)
Mr AK, 51 y, Rx (2)   24-h 149/92 69
                      Day 152/94 70
Office BP 155/100     Night 143/88 65




                            67 (90%)
Mr SX, 68 y, Rx (2)   24-h 150/79 67
                      Day 152/81 68
                      Night 150/78 65




                            70 (98%)
Mrs EK, 62 y Rx (3)   24-h 123/76 71
                      Day 118/75 76
Office 146/82         Night 132/81 61




                            67 (90%)
     NOCTURNAL
“HOME” BLOOD PRESSURE
       IN OSA?


   DESTOUNIS A, CHOLIDOU K, KOLLIAS A, KARPETTAS N, MARKOZANNES E, ALCHANATIS E, STERGIOU GS.
HYPERTENSION CENTER, THIRD UNIVERSITY DEPARTMENT OF MEDICINE, SOTIRIA HOSPITAL, ATHENS, GREECE.
     FIRST UNIVERSITY DEPARTMENT OF RESPIRATORY MEDICINE, SOTIRIA HOSPITAL, ATHENS, GREECE.
                     ASSOCIATION OF AHI
               WITH DIASTOLIC BLOOD PRESSURE




                        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, SOTIRIA HOSPITAL, ATHENS, GREECE.
     FIRST UNIVERSITY DEPARTMENT OF RESPIRATORY MEDICINE, SOTIRIA HOSPITAL, ATHENS, GREECE.
                     ASSOCIATION OF OSA INDICES
                     WITH NOCTURNAL DIASTOLIC
                        HOME BLOOD PRESSURE




   DESTOUNIS A, CHOLIDOU K, KOLLIAS A, KARPETTAS N, MARKOZANNES E, ALCHANATIS E, STERGIOU GS.
HYPERTENSION CENTER, THIRD UNIVERSITY DEPARTMENT OF MEDICINE, SOTIRIA HOSPITAL, ATHENS, GREECE.
     FIRST UNIVERSITY DEPARTMENT OF RESPIRATORY MEDICINE, SOTIRIA HOSPITAL, ATHENS, GREECE.
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
KEY WORDS DETECTING OSA
Symptom       Daytime sleepiness, reduced concentration,
              depression, indefinite complains (headache,
              malaise) at awakening or in the morning,
              marked snoring, frequent awakening during
              the night, nocturia, nocturnal dyspnea (feeling
              of suffocation).

Physical      Obesity, micrognathia.

Examination   Resistant Morning Hypertension
              Nocturnal Hypertension
              Left Ventricular Hypertrophy
              (particularly with normal clinic and home BP)
              Sleep-onset Cardiovascular Events
              (including AF and ventricular arrhythmia)
              Metabolic Syndrome
?

    2003
   CPAP

Effect on Blood
   Pressure
   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
Effect of nCPAP on Blood Pressure
       in Patients with OSA
          Becker et al. Circulation 2003;107:68-73



Randomised 9 weeks nCPAP (32 OSA Subjects)

  Effective CPAP (16)  Mean ABP decrease
                         9.9+/-11.4 mmHg
                            (P 0.01)

  Subtherapeutic (16)  N.S.

              10 mmHg 
    Stroke risk 55%, CHD risk 37%
   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
Effect of CPAP vs Supplemental Oxygen
         on 24h Ambulatory BP




                  Norman et al. Hypertension 2006;47:840-5.
  Blood Pressure Lowering Effects
     of CPAP: A Meta-analysis

                     16 RCTs, 818 subjects


              Mean Ambulatory BP decline
                      (mmHg)

          Systolic: 2.5 (95% C.I. 0.6-4.3)
          Diastolic: 1.8 (95% C.I. 0.6-3.0)


Bazzano, et al. Hypertension 2007; 50:417-23..
 CPAP for hypertension in OSA patients:
     Randomised Controlled Trial




11 hospitals in Spain
340 hypertensives with OSA
3 months CPAP                Duran-Cantolla, et al. BMJ 2010.
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.
CPAP: Determinants of Effective
  Blood Pressure Reduction
     CHARACTERISTICS
         • Obesity (increased BMI)

     BLOOD PRESSURE
         •   Higher baseline blood pressure
         •   Untreated hypertension
         •   Nocturnal hypertension
         •   Resistant hypertension

     OSA FACTOR
         • Severe OSAS AHI >30
         • OSAS with daytime sleepiness

     CPAP FACTOR
         • Compliance (>3-h/night)
         • Long-term use
         • Effectiveness (AHI reduction >50%)
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 Drug
   Treatment in OSA
                  BP     OSA
Beta-Blocker      ++??   -??
Dihydropyridine   +?     +?
ACE Inhibitor     +?     +?
Angio Blocker     +?     +/-?
Aldo Antagonist   ?      ?
Diuretic          +?     +?
Nocturnal Rx      ??     ??
DETECTION OF OSA IN CLINICAL PRACTICE




                   Kario K. Hypertens Res 2009;32:428-32.
MANAGEMENT OF HYPERTENSION IN OSA




                 Kario K. Hypertens Res 2009;32:428-32.
OSA and Hypertension

     STRENGTH OF EVIDENCE

   Direct cause-effect association. ***
   OSA effects on blood pressure. ***
   OSA treatment effects on blood pressure.
   Antihypertensive treatment in OSA   **
    induced hypertension. *

								
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