Medicina del sonno e malattie cardiovascolari
Nicola MontanoMedicina 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’ lavorativaIncremento degli incidenti stradaliAumento di morbidita’ e mortalita’ totali
forte associazione con malattie cardiovascolari, metaboliche ed infiammatorie croniche
Sleep Deprivation
Sleep fragmentationAging, Obstructive Sleep Apnea (OSA), PLMShift work, (snoring)….(newborn babies’parents)
Chronic sleep restrictionHigh pressure work schedulesLifestyle choiceInsomnia
Total sleep deprivationIntense military missionsHealth care workers going on callLifestyle choices e.g. video game, gambling addiction
Autonomic nervous system
Circadian system
SLEEP
Immune system
Neuro- endocrine system
?
? ?
?
(Adapted from Bryant, Trinder & Curtis, Nat Rev Immunol, 2004)
Cardiovascular System
(Somers V. K. et al. N Engl J Med 1993;328:303-307
Cardiovascular
and sympathetic
changes
during sleep
(Somers V. K. et al. NEJM 1993;328:303-307)
Sleep and Autonomic Nervous System
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
Episodi intermittenti di interruzione del respiro durante il sonno
↓alterazione della struttura del sonno
e della ventilazione↓
russamento e sonnolenza diurna
Obstructive Sleep-Apnea (OSA)
OSA - Epidemiology
3-4% of population
Middle-age
Men 4%, Female 2%
1/5 adults has at least mild-OSA
25 million
1.6 million
80.000
OSA - DiagnosisIndagini 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)
prevalence%
AHImean ± 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)
Resistant Hypertension
Cardiovascular Diseases & OSA
HypertensionCongestive Heart Failure
Diastolic dysfunctionSystolic dysfunction
Cardiac ArrhythmiaBradycardiaA-V blockAtrial Fibrillation
Cardiac IschemiaCoronary Artery DiseaseNocturnal S-T Segment DepressionNocturnal 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
Vascular Oxidative Stress
Inflammation
Increased Coagulation
Metabolic DysregulationObesity
Insulin resistance
Leptin resistance
Sympathetic activation
Intermittent hypoxia
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!
(Somers et al, J Clin Invest 1995;96:1897–1904)
Effects of nocturnal CPAP on sleep sympathetic traffic in OSA
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”
(Patruno et al, Chest 2007)
CPAP APAP
B 3 mo.
SAP
(mm
Hg)
105
115
125
135
145
155
165
B 3 mo.
* ns
Effects of CPAP and APAP on cardiovascular risk factors in OSA patients
(Patruno et al, Chest, 2007)
CPAP APAP
B 3 mo.
DA
P (m
mH
g)
65
70
75
80
85
90
95
100
B 3 mo.
ns*
Effects of CPAP and APAP on cardiovascular risk factors in OSA patients
ESH/ISH Recommendations….It is important to consider sleep apnoea in
the characterization of obese patients, especially those with hypertension resistantto 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=4810Hypertension incidence: n=647Follow up of 10 years
- Sleep duration ≤5 hrs/night was associated with a significant increased riskof 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 obesityand diabetes.
Short sleep duration could be a significant
risk factor for hypertension
Sleep & Diseases
Sleep & Diseases
(Spiegel K et al, J Appl Physiol 2005, 99:2008-18)
⇑SNA⇑SNA
(Perciaccante et al, submitted)
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 monitoringPittsburgh Sleep Quality Index (PSQI)Blood pressure and oral glucose tolerance test (OGTT) 24-h ECG Holter recording (spectral analysis of HRV)
NGR“poor sleepers” “good sleepers” p value*
Sex (M/F) 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
Pre DM“poor sleepers” “good sleepers” p value*
Sex (M/F) 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
(Perciaccante et al, submitted)
Night-time sympathetic modulation
Sleep
ANS
“The chicken and the egg” question
Statements
ANS plays a crucial role in triggeringcardiovascular disease
ANS is modulated by sleep and a propercircadian rhythm
Sleep disturbances are associated with ANSalteration and with an increased morbidity
Sleep might reduces cardiovascular risknormalizing the sympathovagal balance
Questions
Could we suggest sleep as a“therapeutical intervention” tonormalize the sympathovagal balance,thus reducing the cardiovascular risk ?
Or should we target the sympathovagalbalance to improve sleep ?
EPWORTH SLEEPINESS SCALEChe 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 mai1 = ho qualche probabilità di addormentarmi2 = ho una discreta probabilità di addormentarmi3 = 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 ………..
< 10: non sonnolenza significativa
> 10: sonnolenza significativa!!!!!!!!
•…..se il vostro ESS score:
“Il segreto della creatività sta nel
dormire bene e aprire la mente alle
possibilità infinite. Cos’è un uomo senza
sogni?”
A.Einstein
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