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