Obstructive Sleep Apnea in Childhood and its Cardiovascular Effects A. Kaditis, MD

Obstructive Sleep Apnea in Childhood and its Cardiovascular Effects

A. Kaditis, MD

University of Thessaly School of Medicine and Larissa University Hospital

Department of Pediatrics and

Sleep Disorders Laboratory

Clinical Presentation and Etiology

Obstructive Sleep Apnea in Childhood

Obstructive Sleep Apnea in Childhood Clinical Presentation

Snoring Apnea Mouth breathing Restless sleep Frequent arousals

Obstructive Sleep Apnea in Childhood Adenoidal-Tonsillar Hypertrophy

Pathogenesis

Obstructive Sleep Apnea in Childhood

Inspiration: The Thoracic Pump

0 cmH2O

-5

-10

Airway Diameter and Respiratory Phase

EXPIRATION INSPIRATION

OSA: Airway-Adenoids-Tonsils (Arens R, et al. AJRCCM 2001;164:698)

Obstructive Sleep Apnea in Childhood-Pathogenesis Model

Pathophysiology

Obstructive Sleep Apnea in Childhood

Intermittent Upper Airway Obstruction and Gas Exchange Abnormalities

Hypercapnia Hypoxia

Cardio-Respiratory Interactions

Respiratory Dysfunction

↕

Cardıac Dysfunction

Upper Airway Obstruction and Cardiac Function

OSA

Defense of the Central Nervous System to Upper Airway Obstruction

Arousal from Sleep

And

Increase in Tone of Pharyngeal Muscles

OSA and Cardiovascular System

Obstructive Sleep Apnea in Childhood

AHI Odds ratio

0-1.3 1.0

1.4-4.4 0.98

4.4-11 1.28

> 11 1.42

Shahar et al. Sleep-Disordered Breathing and Cardiovascular Disease.

AJRCCM 2001;163:19-25

OSA-CV disease-Pathogenesis Quan and Gersh. Circulation 2004;109:951

Obstructive Apnea-Hypopnea

Hypoxia Arousals ↓ Intrathoracic Pressure

Oxidative stress↑ Sympathetic

tone

Endothelial dysfunction-

↓arterial distensibility

Inflammation- metabolic

disturbances

BP abnormalities

Δ in cardiac structure-function

OSA and Inflammation

Obstructive Sleep Apnea in Childhood

Obstructive SDB and CRP Levels in Children

CRP

AHIAHI

Tauman et al. Pediatrics 2004;113:e564

Kaditis et al. AJRCCM 2005;171:282

Log

CRP

AHIAHI

Larkin et al. CRP and AHI: Threshold EffectsCirculation 2005;111:1978

Kaditis et al. Fibrinogen in Children with Sleep-Disordered Breathing. Eur Respir J 2004; 24:790

AHI>5AHI<5Controls

Fib

rin

og

en

(m

g/d

L)

600

400

200

0Kruskal-Wallis

P = 0.002

114 children

3-10 yo

OSA and Insulin Resistance

Obstructive Sleep Apnea in Childhood

de la Eva R, et al. Metabolic Correlates with OSA in Obese Subjects. J Pediatr 2002; 140: 654-9

AHI ≥ 5 AHI < 5

-0.5

0

0.5

1

1.5

2

50 100 150

Relative BMI (%)

Log

insu

lin

Kaditis A, et al. Obstructive SDB and Fasting Insulin Levels in non-Obese Children. Pediatr Pulmonol 2005;40:515

110 children

2-13 yo

Tauman R, et al. Obesity determines Insulin Resistance in Snoring Children. Pediatrics 2005; 116: e66

135 children

8.9 ± 3.5 yo

OSA and Blood Pressure

Obstructive Sleep Apnea in Childhood

BP in Children with OSA

Marcus et al. AJRCCM 1998;157:1098

Kaditis et al. Morning BP in Children referred for Polysomnography.American Thoracic Society Meeting 2006

164 children

2.9-15 yo p < 0.01

Diastolic BP Index

(%)

p < 0.01

AHI≥5 1≤AHI<5 AHI<1

p < 0.01

Elevated Diast BP

For AHI>5 OR 6.9

For 1<AHI<5 OR 3.3

Kaditis et al. BP and Habitual SnoringPediatr Pulmonol 2005;39:408

760 children

4-14 yo

OSA and Cardiac Function

Obstructive Sleep Apnea in Childhood

A. Tal, et al. Ventricular Dysfunction in Children with OSA. Pediatr Pulmonol 1988; 4: 139

Amin et al. Left Ventricular Hypertrophy in Children with OSAAJRCCM 2002; 165:1395

28 subjects with OSA 19 subjects with Primary Snoring Left Ventricular Mass Index higher in OSA AHI significant predictor of

Left Ventricular Mass Index

Amin et al. Left Ventricular Function in Children with SDBAm J Cardiol 2005; 95:801

25 children with AHI>5 23 children with AHI=1-5 15 children with AHI<1 Left Ventricular Mass Index higher in OSA AHI significant (negative) predictor of

Left Ventricular Diastolic Function

Kaditis et al. Nocturnal Cardiac Strain in Children with Obstructive SDB. American Thoracic Society Meeting 2006

-0.6

-0.4

-0.2

0

0.2

0.4

0.6

0 10 20 30

AHI (episodes/hour)

log

BN

P r

atio

AHI ≥ 5 AHI < 5 Controls

R =0.29; p < 0.05

Conclusions-Research Questions

Pediatric SDB is related with mechanisms predisposing to CV morbidity in adulthood

Unknown threshold of SDB severity above which associated morbidity