Nontraditional cardiovascular risk factors in pediatric metabolic syndrome

doi:10.1016/j.jpeds.2005.08.025

The Journal of Pediatrics

Volume 148, Issue 2, February 2006, Pages 176-182

https://doi.org/10.1016/j.jpeds.2005.08.025 Get rights and content

Objective

To study the relationships between nontraditional cardiovascular (CV) risk factors and components of the metabolic syndrome in Native Canadian children, a population at risk of future CV disease.

Study design

CV risk factors were evaluated in a population-based study of a Canadian Oji-Cree community, involving 236 children aged 10 to 19 years.

Results

Using an age- and sex-specific case definition, 18.6% of the children met criteria for pediatric metabolic syndrome. As the number of metabolic syndrome component criteria increased, C-reactive protein, leptin, and ratio of apolipoprotein B to apolipoprotein A1 levels rose (all P < .0001) and adiponectin concentration decreased (P = .0006). Principal factor analysis using both traditional and nontraditional CV risk factors revealed 5 underlying core traits, defined as follows: adiposity, lipids/adiponectin, inflammation, blood pressure, and glucose.

Conclusions

Nontraditional CV risk factors accompany the accrual of traditional risk factors early in the progression to pediatric metabolic syndrome. Furthermore, inclusion of these factors in factor analysis suggests that 5 core traits underlie the early development of an enhanced CV risk factor profile in Native children.

Section snippets

Methods

The methodology of the Sandy Lake Health and Diabetes Project has previously been described in detail.7, 8, 11 In brief, 728 of 1018 eligible residents of Sandy Lake, an Oji-Cree community in northwestern Ontario, participated in a population-based cross-sectional survey to determine the prevalence of type 2 diabetes and associated risk factors. There were 236 participants aged 10 to 19 years, representing participation of 72.6 % of the eligible population in this age range. Signed, informed

Results

Demographic, clinical, and metabolic characteristics of the 236 study participants are shown in Table I. Mean age was 14.9 years (range 10-19), and 61% of participants were female. The vast majority (92.9%) of the children had normal glucose tolerance, whereas 11 participants exhibited impaired glucose tolerance and 5 had diabetes. Fifty-six percent reported a history of smoking cigarettes. Overall, 18.6% of the children met criteria for diagnosis of the metabolic syndrome, and 66.5% exhibited

Discussion

In a comprehensive evaluation of CV risk factors in this high-risk population, the nontraditional factors CRP, adiponectin, leptin, and apoB:A1 are found to accompany pediatric metabolic syndrome and correlate with traditional CV risk factors. Furthermore, inclusion of these emerging metabolic parameters in factor analysis suggests that an expanded set of 5 core traits underlies the early development of an enhanced CV risk factor profile in Native children at risk of future CVD.

This study

References (29)

S. Yusuf et al.
Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries
Lancet
(2004)
A.J. Hanley et al.
Overweight among children and adolescents in a Native Canadian community
Am J Clin Nutr
(2000)
J. Fernandez et al.
Waist circumference percentiles in nationally-representative samples of African-American, European-American and Mexican-American children and adolescents
J Pediatr
(2004)
J.S. Yudkin et al.
Low-grade inflammation may play a role in the etiology of the metabolic syndrome in patients with coronary heart disease
Metabolism
(2004)
B. Isomaa et al.
Cardiovascular morbidity and mortality associated with the metabolic syndrome
Diabetes Care
(2001)
P. Libby et al.
Inflammation and atherosclerosis
Circulation
(2002)
T. Pischon et al.
Plasma adiponectin levels and risk of myocardial infarction in men
JAMA
(2004)
M.P. Reilly et al.
Plasma leptin levels are associated with coronary atherosclerosis in type 2 diabetes
J Clin Endocrinol Metab
(2004)
J. Meigs
Invited commentary: Insulin resistance syndrome? Syndrome X? Multiple metabolic syndrome? A syndrome at all? Factor analysis reveals patterns in the fabric of correlated metabolic risk factors
Am J Epidemiol
(2000)
S.B. Harris et al.
The prevalence of NIDDM and associated risk factors in Native Canadians
Diabetes Care
(1997)

A.J. Hanley et al.

Adiponectin in a Native Canadian population experiencing rapid epidemiological transition

Diabetes Care

(2003)

B.V. Howard et al.

Rising tide of cardiovascular disease in American Indians

Circulation

(1999)

B. Shah et al.

Increasing rates of ischemic heart disease in the Native population of Ontario, Canada

Arch Intern Med

(2000)

S. Li et al.

Childhood cardiovascular risk factors and carotid vascular changes in adulthood

JAMA

(2003)

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: Supported by grants from the National Institutes of Health (91-DK-01 and 1-R21-DK-44597-01), the Ontario Ministry of Health (no. 04307) and the Canadian Institutes of Health Research (CIHR).

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Original articleNontraditional cardiovascular risk factors in pediatric metabolic syndrome

Objective

Study design

Results

Conclusions

Section snippets

Methods

Results

Discussion

Lancet

Am J Clin Nutr

J Pediatr

Metabolism

Cardiovascular morbidity and mortality associated with the metabolic syndrome

Diabetes Care

Inflammation and atherosclerosis

Circulation

Plasma adiponectin levels and risk of myocardial infarction in men

JAMA

Plasma leptin levels are associated with coronary atherosclerosis in type 2 diabetes

J Clin Endocrinol Metab

Invited commentary: Insulin resistance syndrome? Syndrome X? Multiple metabolic syndrome? A syndrome at all? Factor analysis reveals patterns in the fabric of correlated metabolic risk factors

Am J Epidemiol

The prevalence of NIDDM and associated risk factors in Native Canadians

Diabetes Care

Adiponectin in a Native Canadian population experiencing rapid epidemiological transition

Diabetes Care

Rising tide of cardiovascular disease in American Indians

Circulation

Increasing rates of ischemic heart disease in the Native population of Ontario, Canada

Arch Intern Med

Childhood cardiovascular risk factors and carotid vascular changes in adulthood

JAMA

Original article
Nontraditional cardiovascular risk factors in pediatric metabolic syndrome