Adult Heart Diseases Now Seen in Childhood

Adult Heart Diseases Now Seen in Childhood

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Description: Atherosclerosis is a degenerative disease of the vasculature. Multiple etiologies, slowly progressive, and Silent until effects of vascular occlusion or embolization manifests. Mortality from coronary artery disease due to atherosclerosis has decreased in recent decades.

But coronary artery disease is still a leading cause of death and disability in the US, Economic costs and may further increase due to the childhood obesity epidemic.

 
Author: Geetha Raghuveer MD, MPH (Fellow) | Visits: 1592 | Page Views: 1594
Domain:  Medicine Category: Therapy Subcategory: Obesity 
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Short URL: http://medical.wesrch.com/pdfME1LYY66LEFXR

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Contents:
Adult Diseases Now Seen in Childhood
Geetha Raghuveer MD, MPH Cardiologist, Children's Mercy Hospital Associate Professor of Pediatrics University of Missouri, Kansas City 5-1-2010 Conflicts of Interest / Disclosures � None

Atherosclerosis
Degenerative disease of the vasculature. Multiple etiologies. Slowly progressive. Silent until effects of vascular occlusion or embolization manifests �
myocardial infarction, stroke, sudden death, peripheral arterial disease.

Burden of Atherosclerosis
Mortality from coronary artery disease due to atherosclerosis has decreased in recent decades.

Better treatments � Better control of risk factors �

1

Better Treatments

Better control of risk factors Dyslipidemia � statins. statins. Tobacco smoke � Legislation, education. Diabetes treatments. Hypertension treatments.

Burden of Atherosclerosis But coronary artery disease is still a leading cause of death and disability in the US. Economic costs. May further increase due to the childhood obesity epidemic.

2

Childhood Origins � Autopsy Studies Coronary artery stenoses common in United States Korean and Vietnam war victims � healthy youth in their 20s.
Enos et al; JAMA, 1953. McNamara JJ. et al; JAMA, 1971.

Childhood Origins � Autopsy Studies United States teenagers killed in motor vehicle accidents had evidence of atherosclerosis in the coronary arteries on autopsy.
Stary HC. Arteriosclerosis 1989: 9(1 suppl):119suppl):119132.

Pathobiological Determinants of Atherosclerosis in Youth study � Autopsy Studies 15-34 year accidental death 15victims. 3000 cases � 14 centers � Prevalence of gross and microscopic lesions in the coronary arteries.

3

Relationship of atherosclerosis in young men to serum lipoprotein cholesterol concentrations and smoking. A preliminary report from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. JAMA. 1990;264:3018-3024.

Atherosclerosis in Children
Although the atherogenic process begins in the first decade of life there is a long preclinical phase. Intervention beginning in childhood is expected to have the maximum potential for preventing and reversing atherosclerosis.

Pathogenesis and Pathology of Atherosclerosis

4

Arterial Wall
NERVES ADVENTITIAL CELLS

VASCULAR SMOOTH MUSCLE

ENDOTHELIUM

Vascular tone Coagulation Platelet adhesion and aggregation Macrophage migration Lipid transport Vascular growth

Endothelins Nitric oxide Prostacyclin Heparans vWf
VESSEL LUMEN

Arterial Endothelium

Vasoconstrictor-Proliferative. VasoconstrictorVasodilator-Antiproliferative. Vasodilator- Antiproliferative.

Pathology

5

Pathology
Netter

Atherosclerosis Natural History
With permission from Dr. H. McGill

Reduction of Coronary Artery Disease

Cannot be achieved if adults only are targeted for prevention as the disease is end stage by then.

6

Atherosclerosis

DEADLY QUARTET is likely to expedite the disease process.

Lifetime Risk of Childhood Obesity Evidence
In a large cohort of children born in Denmark and followed for over 5 million person-years, a higher BMI during personchildhood was associated with increased risk of coronary artery disease in adulthood.
Baker JL, Olsen LW, Serenson TIA. Childhood Body-Mass BodyIndex and the Risk of Coronary Heart Disease in Adulthood. N Engl J Med. 2007;357:2329-2337. 2007;357:2329-

7

Lifetime Risk of Childhood Obesity Evidence
A follow up of the Harvard Growth Study of 1922 to 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. followMust A. Jacques PF. Dallal GE. Bajema CJ. Dietz WH. Long-term morbidity and mortality of overweight Longadolescents. A follow-up of the Harvard Growth Study of follow1922 to 1935. N Engl J Med. 1992;327:1350-1355. 1992;327:1350-

Lifetime Risk of Childhood Obesity Evidence
A British study involving a 57 year follow up of a cohort also confirmed that allallcause and cardiovascular mortality were associated with childhood BMI when even >75th percentile.
Gunnell DJ, Frankel SJ, Nanchahal K, Peters TJ, Davey Smith G. Childhood obesity and adult cardiovascular mortality: a 57-y follow-up study based on the Boyd Orr 57- followcohort. Am J Clin Nutr. 1998;67:1111-1118. Nutr. 1998;67:1111-

Need for Medical Involvement In Coronary Heart Disease As a Function of Era and Patient Life Stage
Permission from author - Dr. T. Kimball, Cincinnati Children's Hospital
Em br Fe yo tus Ne wb orn Ad ol es ce nt

1950's 1960's-1970's 1970's-1980's 1980's-1990's 1990's-2000's 2010

M ad iddle ult

Y Ad oun ul g t

Eld ad erly ult

8

Immutable Risk Factors for Atherosclerosis Age. Male sex. Family History.

Mutable Risk Factors for Atherosclerosis Modifiable Risk Factors
Source � National Geographic, February 2007

Cholesterol Levels in Various Species
Eur J Clin Nutr 2002;56:S42-52

9

Dyslipidemia
High Total or LDL Cholesterol. Low HDL Cholesterol. High Triglycerides. High VLDL Cholesterol.

Optimal Cholesterol Levels
Total Cholesterol � < 170 mg/dl. LDL - atherogenic. Makes up majority of TC � < 110 atherogenic. mg/dl. HDL - non atherogenic. Made in liver and small atherogenic. intestine. Makes up 25% of TC. Transports surplus cholesterol back to liver and out of body � 45 mg/dl. VLDL - formed in liver, helps transport triglyceride from liver to fat cells. Triglycerides are the main storage form of fatty acids < 100 mg/dl.

10

Dyslipidemia Causes
Inherited Disorders of Lipid Metabolism

Familial Dyslipidemia � 1 in 400. TC > 300 mg%, LDL >240 mg%. Premature onset of coronary artery disease.

Dyslipidemia - Diet and Lifestyle AKA Obesity - Childhood obesity and overweight � 1 in 3. - Premature onset of coronary artery disease likely - ? more likely.

Dyslipidemia - Diet and Lifestyle AKA Obesity
High fat, low fiber foods. Fast foods. Sugar consumption � pop, orange juice. Portion sizes. Sedentary life style. Behavioral, psychological, cultural aspects of eating. Hunger and eating.

11

Dyslipidemia Causes � Diseases
Diabetes. Hypothyroidism. Nephrotic syndrome. Renal failure. Storage diseases. Liver disease � cirrhosis, biliary atresia. atresia.

Dyslipidemia Causes � Drugs
Steroids. Retinoic acid. Thiazides. Thiazides. Anticonvulsants. Beta blockers. Contraceptives. Alcohol. Psychotropics. Psychotropics.

12

Risk Stratification beyond risk factors? Conventional cardiovascular risk factors explain only up to 50% incidence of heart disease and strokes. Unknown risks ??

Risk Stratification beyond risk factors? Risk factor assessment alone may not be entirely sound in predicting atherosclerosis as at every risk factor level there is variation in amount of atherosclerosis due to Genetic factors. Risk factor interaction. Duration of exposure.

A tool that assesses "end organ damage" may be useful.

13

Risk Stratification beyond risk factors?

- Children do not have symptoms of
coronary artery disease. - Sub clinical Markers of Atherosclerosis � (surrogate markers). - Increased carotid artery intima-media intimathickness.

Atherosclerosis in Children Summary
1. Atherosclerosis is a progressive, degenerative disease beginning in childhood BUT SILENT UNTIL ADVANCED. Assessing sub clinical markers should aid in evaluating "end organ damage" as these damage" markers represent the end result of all risk factor exposures. Atherosclerosis may be more prevalent and clinical effects may be manifesting earlier due to the prevailing obesity epidemic.

2.

3.

14

"A man is as old as his arteries." arteries."
Dr. Thomas Sydenham

Carotid Artery Intima Media Thickness

15

Carotid Artery Intima Media Thickness
Non invasive. Easy to perform. No radiation. Can be repeated. Inexpensive.

Carotid Artery Intima-Media Thickness
Carotid artery intima-media thickness is intimaan independent predictor of future cardiovascular events, heart attacks, strokes and death. Progression in carotid artery intimaintimamedia thickness predicted events better than risk factor measurements. "Window to the coronary arteries". arteries"

Population based prospective studies affirming prognostic value of carotid artery intima media thickness assessment
ARIC Atherosclerosis Risk in Communities - 12,841 subjects. CHS Cardiovascular Health Study - 4476 subjects. Increased carotid artery intima media thickness was associated with increased risk of myocardial infarction, stroke or death even after adjusting for other risk factors.

16

Carotid Artery Intima-Media Thickness in Childhood
Epidemiological Studies Bogalusa study and Muscatine study � High childhood body mass index and high childhood cholesterol levels resulted in increased carotid artery intima media thickness in young adulthood.

Carotid artery intima-media thickness in Childhood
Clinical Observational and Case Control Studies

Hypercholesterolemia. Hypertension. Diabetes. Obesity. Tobacco smoke exposure.

17

High Risk Child Population
Familial Dyslipidemia. Dyslipidemia. Obese children with atherosclerosis promoting risk factors. Obese and Familial Dyslipidemia � Increasing.

Multiple risk factors � Deadly Quartet Effect
Berenson et al

Cumulative burden of childhood obesity
Berenson et al

18

"Vascular age" vs. "Chronological age"

Le J, Zhang D, Menees S, Chen J, Raghuveer G. "Vascular Age" is advanced in children with atherosclerosis promoting risk factors. Circ Cardiovasc Imaging. 2010;3:8-14.

Aim
To delineate if children with obesity and atherosclerosis promoting risk factors and children with familial dyslipidemia had premature aging of their arteries.

Methods
"Vascular age" was evaluated by age" comparing the child's CIMT against child' percentile data for a race and sex matched 45 year old.

19

Carotid Artery Ultrasound
(12 yo white male)

CIMT 0.54 mm in a12 year old white male
Howard G, Sharrett AR, Heiss G, et al. Carotid artery intimal-media thickness distribution in general populations as evaluated by B-mode ultrasound. Stroke. 1993; 24: 1297�1304.

Percentile P05 P10 P25 P50 P75 P90 P95

45 yo 0.40 0.44 0.50 0.57 0.66 0.75 0.83

White Men 55 yo 0.45 0.49 0.57 0.66 0.77 0.88 0.96

65 yo 0.50 0.56 0.65 0.76 0.90 1.07 1.25

Results
Obese n=40 Familial dyslipidemic n=30

Age (years) 13.2 � 2.9 White n (%) 35 (88) Male n (%) 23 (58)

12.7 � 3.8 27 (90) 11 (37)

20

Results
Obese n=40 Familial dyslipidemic n=30 Familial

Family History n (%) 29 (73%) Tobacco smoke n (%) 18 (45%) 30 � 4 BMI (kg/m2) Systolic BP 124 � 14
(mmHg)

29 (97%) 7 (23%) 20 � 3* 114 � 13* 64 � 8

Diastolic BP
(mmHg)

66 � 7

*p 3 Risk Factors.

23

CIMT vs. # of Atherosclerosis Promoting Risk Factors

Risk Factor # >3 3

# of patients CIMT(mm) SD (mm) CIMT(mm) 30 0.54 0.06 10 0.53 0.03

P 0.07

Conclusions
"Vascular age" is similarly advanced in children age" with obesity and atherosclerosis promoting risk factors and in children with familial dyslipidemia. dyslipidemia. Estimation of "vascular age" may help further age" stratify children who are at high risk for developing premature atherosclerosis. These children may need intensive management including pharmacotherapy for risk factor modification.

Do Clinic Based Interventions Help?
Valerie Emuakhagbon and Heather Florence* Ashley Sherman MS MS Hongying Dai PhD PhD Dr. Geetha Raghuveer, MD MPH* MPH Children's Mercy Hospital � Dept of Cardiology Children' *University of Missouri-Kansas City School of Medicine Missouri-

BMI and BMI Z Scores. Risk Factor Measures. Vascular Measures.

24

Non Obese Dyslipidemic Children
Visit 1: 18pts Visit 2: 18pts Visit 3: 5pts

Visit 1 - Visit 2 Visit 1-Visit 3

0

2

4

6

8

10

12

14

16

Time in months

BMI Z Score
1.2 1 0.8 0.6 0.4 0.2 0 BMI Zscore V1 BMI Zscore V2 BMI Zscore V3

P = NS

Total Cholesterol (mg/dL)
Visit 1 Visit 2 Visit 3 273 248 231 Optimal level
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