Quantitative Assessment of Apnea-Induced Dynamic Blood Pressure Variations

Full text

Journal of Sleep Medicine & Disorders
Cite this article: Alex RM, Chun HW, Sun-Mitchell S, Watenpaugh DE, Behbehani K (2016) Quantitative Assessment of Apnea-Induced Dynamic Blood Pressure
Variations. J Sleep Med Disord 3(3): 1050.
Central
*Corresponding author
Khosrow Behbehani, Department of Bioengineering,
University of Texas at Arlington, Texas, USA, Fax: 1- 817-
272-5538; Tel: 1- 817-272-5725; Email:
Submitted: 12 March 2016
Accepted: 13 April 2016
Published: 15 April 2016
ISSN: 2379-0822
Copyright
© 2016 Behbehani et al.
OPEN ACCESS
Keywords
•Blood pressure
•Obstructive sleep apnea
•Apnea severity
•Postural effects
•Breath hold
Research Article
Quantitative Assessment of
Apnea-Induced Dynamic Blood
Pressure Variations
Raichel M Alex1, Hyung W Chun2, Shan Sun-Mitchell2, Donald E
Watenpaugh3 and Khosrow Behbehani1*
1Department of Bioengineering, University of Texas at Arlington, USA
2Department of Mathematics, University of Texas, USA
3Department of Integrative Physiology, University of North Texas Health Science Center,
USA
Abstract
Purpose: To characterize obstructive sleep apnea (OSA) induced blood pressure
(BP) variations, using quantitative features derived from BP waveform such as area
under beat-to-beat pressure cycle, slope of systolic and diastolic time series, and pulse
pressure.
Methods: Firstly, to assess the effects of breathing cessation on BP, separate from
sleep effects, multiple breath hold maneuvers were performed by 26 volunteer healthy
subjects (Age:26.05±3.2 years, BMI:24.67±3.45 kg/m2). Effects of apnea severity
and posture on BP variations were studied by varying inter-breath hold intervals and
subject’s postures. Second study was conducted on 5 OSA patients (Age: 53.60±7.40
years, BMI: 33.66±7.27 kg/m2, AHI: 57.94±25.7) during overnight polysomnography,
to validate the ndings.
Results: Proposed features were sensitive to simulated apnea and OSA effects
(p<0.001). Area proved to be responsive to postural changes whereas systolic and
diastolic pressures did not. Furthermore, Area and pulse pressure were sensitive to the
frequency of simulated apnea.
Conclusion: Dynamics of apnea-induced BP variations can be characterized more
thoroughly by the proposed features derived from BP waveform.
INTRODUCTION
Blood pressure (BP) variations elicited by obstructive
sleep apnea (OSA) have been explored in both nocturnal (i.e.
in OSA patients) and awake (simulated apnea) studies using
single-point determinants such as systolic pressure (Systolic),
diastolic pressure (Diastolic) and mean arterial pressure (MAP)
[1-7]. While these features have been valuable, the ability to
record and analyze whole arterial pressure waveform provides
an opportunity to explore additional features for improved
diagnosis, treatment and monitoring. Pulse pressure (Pulse), area
under beat to beat pressure waveform (Area) and rate of rise in
systolic (Systole) and diastolic (Dias lope) pressures are examples
of such features. These features provide useful information about
      
etc. Pulse pressure is an independent risk factor for predicting
myocardial infarction and stroke in middle aged to older adults
where OSA is most prevalent [8,9]. Area depends on heart rate,
arterial constriction and/or vasodilatation [10]. Systole and
Dias lope is as an indicator of the progressive rise in BP due to

        
         

       
   
disruption or other cardiovascular ailments present in OSA
          
multiple breath holds on healthy volunteers. Effects of apnea

       
OSA was assessed in an overnight sleep study of OSA patients.
MATERIALS AND METHODS
Data Acquisition
Continuous non-invasive beat to beat BP monitoring was
  

Behbehani et al. (2016)
Email:
J Sleep Med Disord 3(3): 1050 (2016) 2/6
Central

to intra-arterial and auscultatory pressure measurements, and
         
          
          
          

       

and analysis.
Systolic, Diastolic, MAP, Pulse, Area, Systole, and Dias lope
can be extracted from a continuous BP waveform as shown in
(Figure 1a&1b). Peaks and troughs of the beat to beat pressure
waveform represent Systolic and Diastolic values during each
        
the net pressure generated by heart during each contraction and
computed using: [8].
Area is determined by numerically integrating the pressure
waveform between consecutive diastolic troughs (Figure 1a)
and is computed for each cardiac cycle separately. Systole and
         
(regression) linear line to the systolic and diastolic pressure
values during an apnea event followed by slope computation
(Figure 1b).
Subject Demographics
First, to determine the effect of apnea (breathing cessation)
  
       ) with
no known sleep or cardio-respiratory disorders were recruited.
       
         

Subjects were given complete instructions about the experiments
    
form.
SIMULATED APNEA STUDY
Experimental Protocol
Subjects were asked to avoid caffeinated drinks at least
           


          
completely and hold their breath as long as they can. A nose clip


    


           
BP response, both Protocol A and B were conducted in sitting
           
generated: sitting A, sitting B, supine A and supine B. Each subject
randomly selected a posture, followed by randomization of the
order of protocols within each posture.
Data Analysis
       
BP features were extracted as illustrated in (Figure 1a, 1b)
    
that BP features, both proposed and single-point metrics, show

that temporal separations between apnea episodes or apnea
  vs B) as well as subject’s posture (sitting
vs.   
were carried out using
          
       
using Kolmogorov-Smirnov (K-S) D statistics.
a. Effect of Breath Hold:    
     


b. Effect of Apnea Frequency: Analysis of covariance
     
design was used.
         

Protocol A and B for each posture [17,18].
c. Effect of Posture: As explained earlier, in due consideration
of subject’s comfort, each subject selected either sitting or supine
posture at will, followed by randomization of protocols within
the assumed posture. Therefore, both protocol A and B were
applied in the selected posture before the posture was changed,
Figure 1 Extraction of BP Features. (a) Area, Pulse, MAP, Systolic and
Diastolic during each cardiac cycle. (b) Sys Slope and Dia Slope during



Behbehani et al. (2016)
Email:
J Sleep Med Disord 3(3): 1050 (2016) 3/6
Central

determine postural effect, average of both protocols A and B was
taken in a given posture and paired t-test was conducted.
d. Effect of Breath Hold Duration:   
relation between apnea duration and BP response, we used
linear regression model with BP features as dependent variables

SLEEP APNEA STUDY
Experimental Protocol
   
data was recorded on sleep diagnostic system integrated with
       

time delay.
Data Analysis
        
          
        
waveform into normal
Breathing and OSA events, followed by feature extraction. A
      
        
OSA.
RESULTS

elevation of BP. Detectable and fairly repeatable BP elevation
         

       
cyclical variations in BP during OSA episodes, comparable to the

Simulated Apnea Study
a) Effect of Breath Hold: BP features extracted from each of



      
       
     .   
 

       


b) Effect of Apnea Frequency: During K-S test, Area
        
         
     
 
         
        
followed by log transformation.
    

Diastolic, Area and MAP in sitting posture; and for Systolic,
Pulse and MAP in supine posture (Table 1). Further, there were


(Duration x Protocol) (Table 1).
c) Effect of Posture:       
Protocol A and B were pooled for sitting and supine postures.
vs supine

d) Effect of Breath Hold Duration:   
      
       
transformation was performed on Area and Systole in supine
posture prior to regression analysis. Slope of regression line
         

and MAP in sitting posture.
Sleep Apnea Study
       

     
         
        

breathing (p<0.001).
Figure 2
         




Behbehani et al. (2016)
Email:
J Sleep Med Disord 3(3): 1050 (2016) 4/6
Central
Table 1: 
Posture Effect Systolic Diastolic Area Pulse MAP Systole Dias lope
Protocol 0.010.010.08 0.010.91 

Duration x Protocol 0.010.09 0.01 0.71
Protocol 0.01  0.08 0.07

Duration x Protocol       
    
considered.
Table 2: 
(a) Sitting Posture
Features β0
(Intercept)
β1
(Slope) p-value
Systolic  0.77 0.001
Diastolic   
Pulse   0.09
MAP   0.0008
Area   0.09
SysSlope  0.01 
DiaSlope   
(b) Supine Posture
Features β0
(Intercept)
β1
(Slope) p-value
Systolic   
Diastolic   
Pulse  0.09 
MAP  0.09 
Area(log)   0.89
SysSlope(log)  0.0008 
DiaSlope   

        
        
     

       

DISCUSSION
        
characterization of BP variations during apnea by examining
measures derived from continuous BP waveform as well as single
point measures. Effects of apnea severity and posture were also
     

        
         
breathing cessation. All BP features exhibited sensitivity to

         
due to temporary increase in arterial stiffness resulting from
sympathetically mediated vasoconstriction, or increased cardiac
stroke volume driven by isotropic effects of sympatho excitation,
or both. Moreover, central arterial stiffness increases with aging
- an OSA hallmark – can result in more prominent rise in systolic
than in diastolic pressure resulting in increased baseline pulse
pressure [8]. The combined effect may lead to elevated pulse
        
          
hypertension and OSA exhibited a higher pulse pressure than
those without OSA.
Our results showed an increase in Area under beat to beat
BP waveform. This can be attributed to the increase in either
pressure amplitude or temporal length of pressure pulse. During
initial stages of breathing cessation, heart rate slows down due
to increased vagal tone thereby increasing duration of pressure

       
and heart rate (i.e. lower duration). An overall increase in Area
suggests that, shorter pulse (i.e., increased heart rate) is offset by
the degree of rise in pressure amplitude.
Absence of ventilation reduces arterial O and elevates CO,
      
occluded airway leads to negative intra-thoracic pressure
thereby removing sympathetic inhibition from pulmonary
        
      
       
of Systole and Dias lope during apnea – are in agreement with
   et al [7] and Morgan et al   
shown that repetitive hypoxias – induced by breath-hold – can
cause periodic hypertensive episodes. Similar swings in BP have



     
   
and MAP in both sitting and supine postures (i.e., irrespective of
subject’s posture); Diastolic pressure and Area in sitting posture;
and Pulse pressure in supine position. Possible explanation is

 

Behbehani et al. (2016)
Email:
J Sleep Med Disord 3(3): 1050 (2016) 5/6
Central
Table 3: Average Blood Pressure Features During Simulated and Sleep Study.
Systolic Diastolic MAP Pulse Area SysSlope DiaSlope
Experimental Protocols Pressure

Pressure
  Pressure
   
Simulated
Sitting A
xx

xx 
Sitting B xx

x
xx

x
Study Supine A xx

x
xx 
Sleep
Supine B
xx

x
xx

x
Study
OSA
      

          
pressures was insensitive to these temporal separations.
Postural effect on apnea induced BP variations was examined
since it has been shown that supine posture worsens OSA severity
        
        
proved to be insensitive to postural changes except Area. Area
is the only parameter which depends on both heart rate and BP.

why Area is sensitive to posture. This illustrates that multi-
parameter characterization of BP may reveal differences which
are not discernable through use of single-point parameters.
Magnitude of BP rise indicated by Systolic, Diastolic and MAP
         
This hints that while longer duration apneas result in higher level
of BP, the rate of BP rise may not vary based on duration. All BP
features proposed in this study, were responsive to OSA events as
   
        
simulated apnea might be useful in estimating OSA induced rate
           
           
         
         

         


        
conditions and responses of subjects recruited for simulated
apnea study may be different from OSA subjects, due to age
       
  
         
completely mimic OSA, due to absence of negative intra-thoracic

stimulation to be more dominant in generating apnea induced
neuro circulatory response than intra-thoracic pressure since it

cause similar chemoreceptor stimulation and sympathetic
activation. Moreover, our results indicate that, BP features

to OSA events in older sleep apnea patients.
CONCLUSIONS
This study showed that apnea-induced rapid and spontaneous
   
single-point BP features are complemented with features derived
   
that rate of systolic rise is similar for awake subjects voluntarily
holding breath and OSA events. Apnea severity, subject’s posture
          
    

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          
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useful in predicting risk for coronary heart Disease? The Framingham

9. 
stiffness and pulse pressure in hypertension and cardiovascular

10. Murray WB, Foster PA. The peripheral pulse wave: information

11.           
   
Sleep Apnea: Pathogenesis, Diagnosis and Treatment. Second edn.



Behbehani et al. (2016)
Email:
J Sleep Med Disord 3(3): 1050 (2016) 6/6
Central
         

        
          
     


    


     
pressure responses to voluntary apnea are augmented by hypoxemia.

        

17.         

18. Maxwell SE; O’ 
        

19. 


           
breath-hold, valsalva and Mueller maneuvers in obstructive sleep

Kasai T, Floras JS, Bradley TD. Sleep apnea and cardiovascular disease:

Kario K. Obstructive sleep apnea syndrome and hypertension:
        

        
negative intrathoracic pressure vs. asphyxia during voluntary apnea. J

          
     

       
et al. Positional therapy for obstructive sleep apnea: an objective
         

          

          

Alex RM, Chun HW, Sun-Mitchell S, Watenpaugh DE, Behbehani K (2016) Quantitative Assessment of Apnea-Induced Dynamic Blood Pressure Variations. J
Sleep Med Disord 3(3): 1050.
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