Medicina del sonno e
malattie cardiovascolari
Nicola Montano
Medicina Interna II, Dipartimento di Scienze Cliniche Universita’ di Milano, Ospedale L. Sacco
Key points:
• 1‐ Sleep affects cardiovascular system
• 2‐ Autonomic Nervous System: “the link”
• 3‐ Sleep as a new therapeutic intervention?
Function(s) of Sleep
• Role in learning – “sleeping on it”
improves learning
• Neural effects - role in maintaining
neural plasticity
• Improves quality of wakefulness
– Better alertness, mood, cognition
• Metabolic, immunity, inflammation
regulation
Sleep Deprivation
‰Media ore di sonno:
1910 → 9 hours
2000 → 7.5 hours
‰Ridotta produttivita’ lavorativa
‰Incremento degli incidenti stradali
‰Aumento di morbidita’ e mortalita’ totali
‰ forte associazione con malattie cardiovascolari, metaboliche
ed infiammatorie croniche
Sleep Deprivation
‰Sleep fragmentation
‰Aging, Obstructive Sleep Apnea (OSA), PLM
‰Shift work, (snoring)….(newborn babies’parents)
‰Chronic sleep restriction
‰High pressure work schedules
‰Lifestyle choice
‰Insomnia
‰Total sleep deprivation
‰Intense military missions
‰Health care workers going on call
‰Lifestyle choices e.g. video game, gambling addiction
Circadian system
?
Autonomic
nervous
system
?
Neuroendocrine
system
SLEEP
?
?
Immune system
Cardiovascular System
(Adapted from Bryant, Trinder & Curtis, Nat Rev Immunol, 2004)
Cardiovascular
and sympathetic
changes
during sleep
(Somers V. K. et al. N Engl J Med 1993;328:303-307
Sleep and Autonomic Nervous System
(Somers V. K. et al. NEJM 1993;328:303-307)
Circadian variation in the frequency of
sudden cardiac death
(Mueller et al, Circulation 1987;75:131-138)
Circadian variation in the stroke onset
(Stergiou et al. Stroke 2002;33:1480-1486)
Circadian variation in paroxysmal SVT
(Huang-Lee et al. Chest 1999;115:674-678)
Autonomic circadian rythmicity
(Furlan et al, Circulation 1990;81:537-547)
The case of the
Obstructive Sleep-Apnea (OSA)
‰ Association with car/work accidents
‰ Association with cardiovascular diseases
OSA is a cardiovascular risk factor!
Obstructive Sleep-Apnea
Obstructive Sleep-Apnea (OSA)
Episodi intermittenti di interruzione del
respiro durante il sonno
↓
alterazione della struttura del sonno
e della ventilazione
↓
russamento e sonnolenza diurna
OSA - Epidemiology
‰3-4% of population
‰Middle-age
‰Men 4%, Female 2%
25 million
1.6 million
80.000
‰1/5 adults has at least mild-OSA
OSA - Diagnosis
Indagini diagnostiche
PSG completa
Monitoraggio cardiorespiratorio
Classificazione:
AHI (apnea-hyponea index): 5-15 lieve
15-30 moderata
>30 grave
Apnea: cessazione del flusso aereo >10 s
Ipopnea: riduzione del flusso aereo >70% per almeno 10 s associata ad
una riduzione della saturazione di O2 >3%
SLEEP APNEA
•Makes you sleepy
•Makes you slow
•Makes you crash car
(Royal Automobile Club)
“OSA as first of identifiable causes
of hypertension”
Report of the Joint National Committee on Prevention, Detection, Evaluation and
Treatment of Hight Blood Pressure
(Chobanian AV. JAMA 2003, 289:2560)
Resistant Hypertension
prevalence
%
AHI
mean ± SE
All (n=41)
82.9
24.7 ± 3.2
M (n=24)
95.8
32.2 ± 4.5
F (n=17)
64.7
14.0 ± 3.1
(Logan et al. J Hypertens 2001;19:2271-7)
Cardiovascular Diseases & OSA
‰ Hypertension
‰ Congestive Heart Failure
‰Diastolic dysfunction
‰Systolic dysfunction
‰ Cardiac Arrhythmia
‰Bradycardia
‰A-V block
‰Atrial Fibrillation
‰ Cardiac Ischemia
‰Coronary Artery Disease
‰Nocturnal S-T Segment Depression
‰Nocturnal Angina
‰ Cerebrovascular Disease
OSA - Arrhythmias
OSA - Arrhythmias
OSA - Arrhythmias
(Circulation. 2004;110:364-367.)
Conclusions —………..a strong association exists between OSA and AF, such
that OSA is strikingly more prevalent in patients with AF than in high-risk
patients with multiple other cardiovascular diseases.
Sleep events in OSA
‰ Hypoxemia
‰ Hypercapnia
‰ Intrathoracic Pressure Changes
(Muller maneuver)
‰ Arousals
(Somers et al, J Clin Invest 1995;96:1897–1904)
(Somers et al, J Clin Invest 1995;96:1897–1904)
OSA - Mechanisms
‰Endothelial Dysfunction
Intermittent
hypoxia
‰Vascular Oxidative Stress
‰Inflammation
‰Increased Coagulation
Sympathetic
activation
‰Metabolic Dysregulation
‰Obesity
‰Insulin resistance
‰Leptin resistance
Sleep
Deprivation
Circadian variation in the frequency of
sudden cardiac death
(Mueller et al, Circulation 1987;75:131-138)
Sudden cardiac death in OSA
Why should we put such an effort in
diagnosing OSA?
Because we can successfully treat it!
Effects of nocturnal CPAP on sleep
sympathetic traffic in OSA
(Somers et al, J Clin Invest 1995;96:1897–1904)
572 pts from 12 RCTs
“…Since hypertension has a multifarious origin, vascular
remodeling is likely to represent the last, and maybe definitive factor
that contributes to the maintenance of hypertension despite the
reduction of all neurohumoral, inflammatory, endothelial, metabolic,
and other promoting factors”…
“To this regard, we should have to wonder whether a different effect
on BP could be obtained starting the CPAP treatment as soon as
hypertension is diagnosed in patients with concomitant OSA”
Effects of CPAP and APAP on cardiovascular
risk factors in OSA patients
165
CPAP
APAP
*
ns
SAP (mmHg)
155
145
135
125
115
105
B
3 mo.
B
3 mo.
(Patruno et al, Chest 2007)
Effects of CPAP and APAP on cardiovascular
risk factors in OSA patients
CPAP
APAP
*
100
ns
95
DAP (mmHg)
90
85
80
75
70
65
B
3 mo.
B
3 mo.
(Patruno et al, Chest, 2007)
ESH/ISH Recommendations
….It is important to consider sleep apnoea in
the characterization of obese patients,
especially those with hypertension resistant
to conventional drug therapy [736–739]…..
Furthermore, hypertensive patients, who are
classified as ‘‘non-dippers’’ on ambulatory
pressure measurements, should be
investigated for obstructive sleep
apnoea……
Sleep deprivation:
a new cardiovascular
risk factor !
Sleep & Diseases
Sleep & Diseases
Total Sleep Deprivation
Partial Sleep Deprivation
(Meier-Ewert K et al, JACC 2004, 43:681-88)
Sleep & Diseases
Longitudinal study, n=4810
Hypertension incidence: n=647
Follow up of 10 years
- Sleep duration ≤5 hrs/night was associated with a significant increased risk
of hypertension (HR 2.10; 95% CI, 1.58 to 2.79) in subjects 32-59 years.
- The increased risk continued to be significant after controlling for obesity
and diabetes.
Short sleep duration could be a significant
risk factor for hypertension
Sleep & Diseases
Sleep & Diseases
⇑SNA
⇑SNA
(Spiegel K et al, J Appl Physiol 2005, 99:2008-18)
Autonomic nervous system, cardiovascular risk
factors and sleep quality
Hypothesis: Poor sleep quality is associated with an increased
prevalence of hypertension and metabolic disturbances
through an increased sympathetic activation
Population: 149 non-obese subjects enrolled from the population
referring to an outpatient clinic for metabolic diseases
screening
Protocol:
Nocturnal cardiorespiratory monitoring
Pittsburgh Sleep Quality Index (PSQI)
Blood pressure and oral glucose tolerance test (OGTT)
24-h ECG Holter recording (spectral analysis of HRV)
(Perciaccante et al, submitted)
NGR
“poor sleepers”
“good sleepers”
8\6
36\20
Age (years)
49.48 ± 6.12
47.16 ± 5.89
NS
BMI (kg/m²)
27.18 ± 4.20
26.77 ± 5.03
NS
Glycemia '0 (mmol/l)
4.63 ± 0.50
4.72 ± 0.44
NS
Glycemia '120 (mmol/l)
5.68 ± 0.87
5.79 ± 0.75
NS
HOMA-Index
4.02 ± 1.56
1.92 ± 1.04
0.001
Fasting plasma insulin (µU/ml)
18.52 ± 7.32
8.62 ± 4.12
0.001
SBP
135.71 ± 3.85
126.47 ± 9.22
0.001
DBP
80.04 ± 3.92
75.47 ± 5.01
0.005
HR (bpm)
70.04 ± 9.78
68.89 ± 11.09
NS
Sex (M/F)
p value*
Pre DM
“poor sleepers”
“good sleepers”
7\3
8\2
Age (years)
53.00 ± 4.97
51.28 ± 6.07
NS
BMI (kg/m²)
28.02 ± 2.56
27.22 ± 3.17
NS
Glycemia '0 (mmol/l)
5.45 ± 0.57
5.41 ± 0.69
NS
Glycemia '120 (mmol/l)
8.63 ± 1.82
8.48 ± 2.39
NS
HOMA-Index
4.12 ± 0.43
3.12 ± 0.45
0.001
Fasting plasma insulin (µU/ml)
17.74 ± 5.10
13.10 ± 1.55
0.03
SBP
135.02 ± 4.07
123.33 ± 8.76
0.02
DBP
79.29 ± 1.89
71.67 ± 5.16
0.004
HR (bpm)
74.75 ± 10.02
72.82 ± 12.74
NS
Sex (M/F)
p value*
Night-time sympathetic modulation
(Perciaccante et al, submitted)
“The chicken and the egg”
question
Sleep
ANS
Statements
‰ ANS plays a crucial
cardiovascular disease
role
in
triggering
‰ ANS is modulated by sleep and a proper
circadian rhythm
‰ Sleep disturbances are associated with ANS
alteration and with an increased morbidity
‰ Sleep might reduces cardiovascular
normalizing the sympathovagal balance
risk
Questions
‰Could we suggest sleep as a
“therapeutical
intervention”
to
normalize the sympathovagal balance,
thus reducing the cardiovascular risk ?
‰Or should we target the sympathovagal
balance to improve sleep ?
EPWORTH SLEEPINESS SCALE
Che probabilità ha di appisolarsi o di addormentarsi nelle seguenti situazioni, indipendentemente
dalla sensazione di stanchezza?
La domanda si riferisce alle usuali abitudini di vita nell’ultimo periodo.
0 = non mi addormento mai
1 = ho qualche probabilità di addormentarmi
2 = ho una discreta probabilità di addormentarmi
3 = ho un’alta probabilità di addormentarmi
1. Seduto mentre leggo
………..
2. Guardando la TV
………..
3. Seduto, inattivo in un luogo pubblico (a teatro, ad una conferenza)
………...
4. Passeggero in automobile, per un’ora senza soste
………..
5. Sdraiato per riposare nel pomeriggio, quando ne ho l’occasione
………..
6. Seduto mentre parlo con qualcuno
………..
7. Seduto tranquillamente dopo pranzo, senza aver bevuto alcolici
………..
8. In automobile, fermo per pochi minuti nel traffico
………..
Somma ………..
•…..se il vostro ESS score:
< 10: non sonnolenza significativa
> 10:
sonnolenza significativa!!!!!!!!
“Il segreto della
creatività sta nel
dormire bene e aprire
la mente alle
possibilità infinite.
Cos’è un uomo senza
sogni?”
A.Einstein