HEART FAILURE & Co.
9-10 April 2010, Milan
Genders and Heart Failure:
Differences and Analogies
Heart Failure and Sleep Disorders:
Different Dreams in Genders?
Maria Teresa La Rovere, MD, FESC
Fondazione Salvatore Maugeri, IRCCS,
Istituto Scientifico di Montescano, Pavia, ITALY
Divisione di Cardiologia
Sleep
=
Biological
function
necessary
for optimal
day-time
functioning
Istituto Scientifico di Montescano
Insufficient / Poor Quality Sleep
• Personal or Societal Influences
• Secondary Effects of Other
Health Problems
• Severe Primary Sleep Disorders
Istituto Scientifico di Montescano
Sleep
Disordered
Breathing
an increasingly
recognised
public health burden
Istituto Scientifico di Montescano
Polysomnography
-Frequent Awakenings
- Arousals
- Little Slow Wave
(delta or stage 3-4)
Sleep
=
Light- Nonrestorative
Sleep
Day-time sleepiness
and impaired day-time
function
Istituto Scientifico di Montescano
Personal or Societal Influences
Role of……….
Wife
Mother
Caregiver for parents
Worker
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Sex Differences in Sleep
Variables
• Sleep variables analyzed in the
absence and presence of a catheter
for blood sampling in order to
examine possible sex differences in
vulnerability to this disturbance
Istituto Scientifico di Montescano
F Latta et al, Sleep 2005
Total Sleep Time (min)
Age and sleep in woman
Sleep Efficiency (%)
Stage 1 (min)
Stage 2 (min)
450
400
350
300
250
200
150
100
50
0
Stage 3-4 (min)
REM (min)
*
* p <0.01
*
*
20-44 yrs
45-54 yrs
*
*
*
55-70 yrs
Total Sleep Time (min)
Hormone replacement therapy (HRT)
and sleep in woman older than 55
Sleep Efficiency (%)
Stage 1 (min)
Stage 2 (min)
400
p =0.06
Stage 3-4 (min)
350
REM (min)
300
250
200
* p < 0.01
150
*
100
*
50
0
Without HRT
*
*
With HRT
C Sahlin et al, Sleep Medicine 2009
Sleep in Women
Istituto Scientifico di Montescano
C Sahlin et al, Sleep Medicine 2009
Poor Quality Sleep and Health
Problems
%
90
Symptom Burden on QoL in HF
80
70
60
50
40
30
20
10
0
Istituto Scientifico di Montescano
CH Zambroski et al, Eur J Card Nur 2005
Severe/
very
severe
Moderate
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CH Zambroski et al, Eur J Card Nur 2005
Stressful Sleeping in HF
Istituto Scientifico di Montescano
NS Redeker et al, Heart and Lung 2006
Severe Primary Sleep Disorders
Sleep Related Breathing Disorders
•2% to 4% of middle- aged adults
•25% of older populations
• Male /female prevalence ratio 2:1 – 3:1
Istituto Scientifico di Montescano
Gender Differences in Sleep
Disordered Breathing
• Definitions
• Prevalence
• Pathogenesis
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Sleep Disordered Breathing
Recurrent Bouts of Ventilatory Overshoots and Undershoots
hyperventilation
hyperventilation
hyperventilation
hyperventilation
hyperventilation
Lung volume
hypopnea
apnea
hypopnea
apnea
hypopnea
desaturation
desaturation
desaturation
SaO2
desaturation
desaturation
Apnea: cessation of airflow for more than 10 sec
Periodic Breathing
Hypopnea: reduction of airflow to more than 50% of normal,
usually in association with a reduction in SaO2
Istituto Scientifico di Montescano
Types of Periodic Breathing:
Obstructive
•Recurrent episodes of apnea and/or hypopnea due to
complete or partial collapse of the pharinx during sleep
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Obstructive Apnea/Hypopnea
Airway opens
Airway obstructs
Oronasal
flow
Chest
movement
Abdom.
movement
Paradoxing
SaO2
Blood oxygen decreases
Istituto Scientifico di Montescano
Types of Periodic Breathing:
Central (CS Respiration)
• Recurrent episodes of apnea or
hypopnea due to complete or partial
withdrawal of central respiratory drive
to the muscles of respiration
Respiratory
motoneurons
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Central Apnea/Hypopnea
Oronasal
flow
Chest
movement
Abdom.
movement
SaO2
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Mixed Apnea/Hypopnea
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Gender and OSAS Syndrome
• Although there is a higher prevalence of
OSAS in males, OSAS in not rare in women
Istituto Scientifico di Montescano
F Kapsimalis et al, Sleep 2002
Clinical Underrecognition of OSAS
in Women
• Different Symptoms
• Different Severity of Symptoms
• Underreport of Symptoms
SDB: the Role of Age, Gender and BMI
(Cleveland Family Study)
30
35
40
45 50
55
60
65
70
Baseline Age (yrs)
PV Tishler et al. JAMA 2003;289:2230-7
Sleep Breathing Disorders in the US
Female Population
• Data from the 2007 Sleep in America Poll
of the National Sleep Foundation
• 1254 women
• Questionnaire including self-reported
snoring, witnessed apneas, daytime
sleepiness hypertension, obesity
• 25% of the female population found to be
at high risk for OSAS
F Kapsimalis et al, J Women’s Health 2009
Hormonal Status and SDB
T Young et al, Am J Resp Crit Care Med 2003
Hormone Replacement Therapy and
SDB
E Shahar et al, Am J Resp Crit Care Med 2003
Prevalence of SDB in HF and Frequency
of the Obstructive and Central Type
N
Criteria
Prevalence
Central
Obstructive
Javaheri et al., 2006
100
AHI  15/h
49 %
76 %
24%
Oldenburg et al., 2007
700
AHI >15/h
53 %
63 %
37 %
Wang et al., 2007
218
AHI > 15/h
46 %
45 %
55 %
Montescano, 2007
139
AHI > 15/h
58 %
89 %
11 %
Vazir et al, 2007
55
AHI > 15/h
53 %
72 %
28 %
Macdonald et al., 2008
108
AHI > 15/h
61 %
51 %
49%
Yumino et al., 2009
218
AHI > 15/h
46 %
45 %
55 %
52 %
Istituto Scientifico di Montescano
63 %
37 %
Istituto Scientifico di Montescano
90
80
70
60
50
40
30
20
10
0
139
Females
561
Males
%
SDB
OSA
CSA
O Oldenburg et al, Eur J Heart Fail 2007
Disordered Breathing and Mortality in HF
1.00
Proportion surviving
PB duration < 120 min
0.95
N=397
0.90
N=88
PB duration  120 min
0.85
Log-rank Chi-square=12.2
p= 0.0005
0.80
0
1
2
3
4
5
6
7
8
9
10
11
12
Time (months)
Javaheri S et al, JACC 2007
Pinna GD et al, Eur J Heart Fail 2009
1.0
Normal
NormalBreathing
Breathing(n=235)
(n=235)
Proportion Surviving
0.9
0.8
N=380
0.7
Periodic
PeriodicBreathing
Breathing(n=145)
(n=145)
N=164
0.6
Log
LogRank
Rank9.25
9.25
PP==0.0023
0.0023
0.5
0.4
0
10
20
30
40
50
60
Time (months)
La Rovere MT et al, Eur J Heart Failure 2007
Istituto Scientifico di Montescano
Wang H et al, JACC 2007
Pathogenesis of SDB
ANATOMICAL PREDISPOSITION TO AIRWAY CLOSURE
EFFECTS OF SLEEP ON VENTILATORY CONTROL AND THE
MECHANISMS UNDERLYING APNEAS
Controlled Variables
CNS
Respiratory Control
Centers
Respiratory
Muscles
Lungs
PaO2
PaCO2
Chemoreceptors
Negative feedback system
Istituto Scientifico di Montescano
PaCO2 (mmHg)
Unmasking a sensitive
apnea threshold
Sleep
45
40
Apnea threshold
VT
t
Istituto Scientifico di Montescano
Upper Airway Muscle Activity in Normal
Woman: Influence of Hormonal Status
Peak phasic activity
Istituto Scientifico di Montescano
Expiratory tonic activity
RM Popovic et al, J Appl Physiol 1998
Upper Airway Muscle Activity in Normal
Woman: Influence of Hormonal Status
Peak phasic
activity
Istituto Scientifico di Montescano
RM Popovic et al, J Appl Physiol 1998
Gender Contribution to Mechanical
Instability of the Upper Airway During Sleep
Istituto Scientifico di Montescano
JP Kirkness et al, J Appl Physiol 2009
Effect of Testosterone of the Apneic
Threshold in Women during NREM Sleep
Baseline
Istituto Scientifico di Montescano
On Testosterone
XS Zhou et al, J Appl Physiol 2003
Pathogenetic Factors in Central Sleep Apnea
in Patients with Heart Failure
1. Hemodynamic Factors: decreased CO, increased PCP
2. Chemoreflex Hypersensitivity
15
3.Hyperventilation
Chua et al,
Eur Heart J 1997
Minute Ventilation
PaCO2 (mmHg)
p=.00002
14
13
P=0.04
40
30
12
Fanfulla et al,
20
Chest 1998
11
10
10
N
CS
0
N
CS