Early Detection of

Cardiovascular Risk Factors in

Infant and Children
Sukman T. Putra,MD,FACC,FESC
Dept.of Cild Health University of Indonesia,
Dr.Cipto Mangunkusumo, Jakarta, INDONESIA
 Cardiovascular
Congenital HD,
Burden of Disease
0.40%
The leading
cause of death
RF / RHD, 0.40%
Other, 13%

Diseases of the globally in 2020

arteries, 4% (WHO)
High blood
pressure, 5%

Congestive heart
failure, 6%

Coronary heart
Stroke, 18% disease, 54%,
 The FACTS

Cardiovascular Disease : now is a Global

Health Problem
 a leading cause of death in 2020
(in 1999 the 6th rank)
 CVD 59% of global death rate
(31.7 millions /year)
 85% of catdiovascular disease
in low-middle income country
WHO, 1999
Outline
 Atherosclerosis in the young age
 Risk factors & pathogenesis
cardiovascular disease
 Non invasive assessment of preclinical
Atherosclerosis
 Primary prevention of Atherosclerotic
Disease in Childhood
 Conclusion
The Aims
To review the early detection of
the cardiovascular risk factors in
childhood, and
how to prevent the process of
atherosclerosis in later life
A time for Action !

Berenson G. Am J. Prev Med 2009;37(S)

Evidence of Atherosclerosis in the
theYoung age
 US soldier killed in Vietnam,
45% had gross atherosclerosis and 5%
severe coronary atherosclerosis
 Young American children killed
in accident , 50% had early sign
of atherosclerosis
 Nation wide autopsy based study
(Japan) : 29% fatty streaks in aorta aged
< 1 year and 3.1% in coronary arteries
aged
1-9 years
JAMA 1971;216: 1185-7
Atherosclerosis 1988; 72:143-76
 Prevalence of Fibrous-plaque
lesion (204 autopsy)

Aorta Coronary artery

60 70

60
50

50
40
40
30
30

20
20

10 10

0
0
2-15 16-20 21-25 26-39
2-15 16-20 21-25 26-39
age(yrs)
Age (yrs)

Berenson GS et al. NEJM. 1998;338:1650-6

 Atherosclerosis
Cardiovascular Risk Factors

Infant Adult

Asymptomatic High mortality rate

 TRADITIONAL RISK INTRINSIC RISK EMERGING RISK
FACTORS FACTORS FACTORS
Hyperlipidemia
Obesiyi/ Inactiviy Genetic predisposition Inflammation /iSystemic
Diabetes Environment Infection .Cytokines, CRP
Smoking , Hypertension Susceptibility Homocysteine

VASCULAR ENDOTHEL STRESS AND DYSFUNCTION

Increasing of Decreasing Increasing Hyperplasia intima

leucocyte bioaviabilty Endothel inflamm. Smooth muscle
adhesion NO response Migrasi/proliferation

Formation of atherosclerotic Plaque

Plaque activation ,Trombosis/vasospasm
Decreasing “blood flow”
Pediatrics. 2007;
119:1683-90 CARDIOVASCULAR EVENTS & DISEASE DEVELOPMENT
 Atherosclerosis
is a complex pathological
condition that begin in early
childhood

Clinical manifestation of the disease

appear in the late adulthood to
old age
 Identification
of children who are at risk for
Atherosclerosis

Early intervention to decrease the

Atherosclerotic process
preventing or delaying
cardiovascular disease
 Pathological Determinants
Atherosclerosis in the Youth
Bogalusa Heart Study

Necropsy evaluation
Atherosclerotic lesions begins in individuals
from
2-39 years old
Evidence : classic vascular risk factors are
relevant to these initial stages
of vessel pathology
PDAY research group :
Atherosclerosis. 2002;160: 441-448
Arterioscler.Thromb Vasc Biol.2000;20:1998-2004
Stages of Atherosclerosis
 ATHEROSCLEROSIS:
Pathology, Pathogenesis, Complications, Natural History
Leeson P. Pediatrics 2007;6: 1203-06
Natural history of Atherosclerosis
 Transition from risk factors to atherosclerosis mediated
by endothelial dysfunction
Pharmacological Report 2006;58:Suppl 33-40
 Impaired FMD(%) in Famalial
Hypercholesterolemia

Celermejer DS. Heart 2006;92:1701-1706

 Obesity/
Overweight
 Now increasing globally
The obese children more likely to be
obese in adulthood
 Metabolic syndrome
increased CV risk factors
(OR: 14.6, 95% CI:2.8-45.3 at 25 yrs
follow up compared to gen.population
Pediatrics.2007;120:340-5
 Obesity/
Overweight
BMI has (+) correlation with more
extensive atherosclerosis in the
aorta and coronary arteries
Pediatrics.2007;120:340-5
 Lifetime Risk of Childhood
Obesity Evidence
In a large cohort of children born in
Denmark & follow over 5 million person
– years a higher BMI during
childhood was associated with
increased risk of coronary
artery disease in adulthood
Baker et al. N.Eng J.Med 2007;357:2329-2337
Lifetime Risk of Childhood
Obesity Evidence
A follow up of the Harvard Growth Study of
1922 t0 1935 showed that being
overweight in adolescence
resulted in a relative risk of coronary
artery disease mortality of 2.3,
independent of adult weight after 55 years of
follow up
Must et al. N.Engl J.Med 1992;327:1350-55
The prevalence of obesity in school age children
in Indonesia
Investigators Province of Indonesia Characteristics of Prevalence (%)
children

Satoto’98 National Urban’89

Boys 4.6
Girl
5.9
Urban’92
Boys
Girls 6.3
1995 8.9
4.6

Kamelia’95 North Sumatra Public elementary school 9

Private elementary school
20
Ismail’95 Central Java Elementary school 8.5

Djer’98 Jakarta Elementary school

Boys 12.3
Girls
6.3

Meilany’02 Jakarta Private elementary school 27.5

7/16/2011 30
 Dyslipidemia
NCEP : Values > 95th percentile
Disorders of lipoprotein metabolism

 increased total cholesterol (TC)

 high- LDL
 low- HDL
 high triglyseride
 The mean total cholesterol level and the prevalence of
hypercholesterolemia in school-age children in Indonesia

Investigators Boys/ Mean cholesterol Prevalence of

Girls (mg/dl) hypercholesterolemia (%)
Pelupessy Boys 161.30
Girls 160.08
Djer 180.3 25

Munir 195.7 31

Meilany 226.6 33.1

Andriastuti 166.7 16

Gerung 166.2

Wulur & Boys 179.46 28.4

Pieter Girls 180.95
7/16/2011 32
Dyslipidemia
Definition of pediatric dyslipidemia as one or
more of the following serum lipoprotein profile
findings
•Total cholesterol (TC) >200 mg/dL
(5.18 mmol/L)
•Low-density lipoprotein cholesterol (LDL-C)
>130 mg/dL (3.36 mmol/L)
•High-density lipoprotein cholesterol (HDL-C)
<40 to 45 mg/dL (1.0 mmol/L)
•Triglycerides >150 mg/dL (1.7 mmol/L) in
adolescents and >130 mg/dL (1.47 mmol/L) in
younger children
 Epidemiology
• Bogalusa Heart Study 80
– Risk factors increased 70
fatty streaks and
fibrous plaques 60
– RF evaluated BMI, SBP, 50
serum TG and LDL
40 Aorta
– 3-4 RF = 8 x risk of
fatty streaks in 30
coronary arteries and Coronary
20
12 x risk of fibrous Arteries
plaques 10
• PDAY (autopsies 15- 0
19)- 10% CA & 30%

rs

rs
s

21 s
Yr

r
5Y

9Y
0y
aortas
15

-2

-2

-3
2-

16

26
Berenson GS, Srinivasan SR, Weihang B, Newman WP, etal. Association between multiple cardiovascular risk
factors and atherosclerosis in children and young adults. N Engl J Med 1998;338:1650-6.
 Effect of Multiple risk factors on the extent
of atherosclerosis

Berenson GS, et al N Engl J Med.1998;338:1650-6

Smoking
A modifiable risk factors of
atherosclerosis
teenagers who smoke

Are likely to continue smoking

in adulthood
increasing risk of
Early cardiovascular disese
The influence of Smoking on prevalnece of Atheroslerosis in
the aorta and coronary arteries in chldren & young adults
Family history
 Independent risk factors of CVD
 Children whose parents/grandparents
had CHD or stroke at early age

Twice the risk of cardiovascular

diseasein the middle-aged adults

JAMA 2004;291:2204-11
Non-invasive methods to
assess precelinical
Atherosclerosis

1. Functional measures
Flow mediated dilation (FMD)

2. Structural measures
Intima media thickness (IMT)
Distensibility
Pulse wave velocity
 Flow Mediated
Dilation(FMD)
Brachial
artery

To measure the
vasodilator response
showing the realease
NO (nitrix oxide)

Decreased FMD :
ENDOTHELIAL DYSFUNCTION “shear stress “
which is a RISK FACTOR ofCVD
phenomen induced
in later life
vasorelaxation
 Intima Media Thickness

 Measurement of anatomic changes of the

arterial wall (thickening intima &media)
 Carotid intima media thickness (cIMT)
marker of atherosclerosis in
children & young adults
 Measuring the increased arterial wall
in neonates LBW, IUGR and familial
hypercholesterolemia
YANG Xiae-zheng et al. Cin Med J 2007:120(5):359- 362
Relationship FMD(%) to risk factors in asymptomatic
subjects (n=500) : Cited from Celermejer 2002
Relationship between
Childhood risk factors &
Carotid IMT
 Therapaeutics Strategies for
Vascular restoration in early life

1.Lifestyle modification- exercise

training
Regular physical exercise for 6 weeks
improved endothelial function and reduced
central adiposity and overweight

2.Nutrient supplements-dietary
modification
L- arginine supplementation
improved endothelial function
 Therapaeutics Strategies for
Vascular restoration in early life
3. Pharmacological risk factor
modification
Lipid lowering therapy improves endothelial
function (Statin treatment)
4. Gen and cell based therapies for
atherosclerosis
Promising tools for both protection and
restoration of myocardium
Target : antioxidant enzymes &
anti-inflammatory cytokines

Inter. J Cardiology 2006;109: 152-159

 Primary Prevention of
Atherosclerotic Disease in Childhood

PDAY :
Atheroscleosis begins in childhood

It would be effective to start

to control the risk factors in
early life
 Primary Prevention of
Atherosclerotic Disease in Childhood

It is NOT recommended to screen

everychild to look for atherosclerosis
risk factors

GUIDELINES for cardiovascular risk

reduction in children & adolescence
(AHA recommendation)
 Primary Prevention of
Atherosclerotic Disease in Childhood
Recommendation to screen children & adolescents to
look for atherosclerosis risk factors :
who have one or more the following risk :
 Family history of early cardiovascular events
( < 55 yrs for men, < 65 yrs for women),
high cholesterol, high lipis or diabetes
 Overweight/obesity, hypertension, dyslipidemia
insulin resistance
 High risk diseases (familial hypercholesterolemia
DM, chronic kidney disease,Kawasaki disease,
CHD, survivor childhood cancer
(start after 2 yrs -10 yrs :BMI,lipid profile,blood sugar)
 Conclusion
 Based on the existing evidence that the
process of atherosclerosis begins in childhood
and clinical manifestation in the adult and
old age.
 Early identification of CV risk factors play an
important role for prevention or intervention
to prevent the clinical manifestation in later
life
 Non-invasive assessment of vascular function
is enable to detect the pre-clinical stages of
atherosclerosis