Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study

doi:10.1016/S0140-6736(01)06525-4

The Lancet

Volume 358, Issue 9291, 27 October 2001, Pages 1400-1404

https://doi.org/10.1016/S0140-6736(01)06525-4 Get rights and content

Summary

Background

Epidemiological studies suggest that obesity-induced atherosclerosis may start in childhood, but this process has never been demonstrated. We looked for arterial changes and investigated their relation to cardiovascular risk factors in obese children.

Methods

Non-invasive ultrasonographic measurements were made in 48 severely obese children and 27 controls to investigate arterial mechanics and endothelial function. Plasma lipid concentrations, indices of insulin resistance, and body composition were assessed in the obese children.

Findings

The obese children had significantly lower arterial compliance than the healthy controls (median 0·132 [0·022–0·273] vs 0·143 [0·112–0·237] mm².mm Hg; p=0·02) and lower distensibility (0·60 [0·10–1·00] vs 0·70 [0·50–1·10] mm Hg⁻¹.10⁻²; p=0·0001). Conversely, the obese children had higher values than the controls for wall stress (3·36 [2·00–5·01] vs 2·65 [2·13–3·54] mm Hg.10²; p=0·0001) and incremental elastic modulus (1·68 [0·72–10·8] vs 0·96 [0·64–1·47]; p=0·0001). Endothelium-dependent and independent function were also lower in the obese than in the control children. An androld fat distribution was positively correlated with indices of insulin resistance and plasma triglyceride concentrations and was negatively correlated with plasma HDL-cholesterol concentration and arterial compliance. Endothelial dysfunction was correlated with low plasma apolipoprotein A-l and with insulin resistance indices.

Interpretation

Severe obesity in children is associated with arterial wall stiffness and endothelial dysfunction. Low plasma apolipoprotein A-l, insulin resistance, and android fat distribution may be the main risk factors for these arterial changes, which are of considerable concern as possible early events in the genesis of atheroma.

Introduction

Obesity in adults is strongly linked to cardiovascular disease mainly through an increased risk of insulin resistance and other abnormalities including dyslipidaemia and high blood pressure.¹ There is substantial evidence that obesity in childhood lays the metabolic groundwork for adult cardiovascular disease.² Furthermore, a 55-year follow-up study showed that adults who were overweight in adolescence had an increased risk of morbidity and mortality from cardiovascular diseases, independently of adult weight.³ These findings were confirmed in a 57-year follow-up study.⁴ Although these studies have shown that childhood obesity is a risk factor for coronary heart disease, there is no available information on the course of vascular changes in obese children and adolescents. The increasing prevalence of childhood obesity in more developed countries brings with it a pressing need to find out whether obesity-associated atherogenesis begins in childhood.

New echotracking techniques can be used to investigate the mechanical properties of the common carotid artery and the endothelial function of the brachial artery;5, 6, 7 changes in these functions are established markers for coronary-artery atherosclerosis.⁷ We used these techniques to investigate whether severely overweight children show early abnormalities of the arterial wall and endothelial dysfunction. In addition, we investigated the relation between these arterial features and metabolic cardiovascular risk factors.

Section snippets

Study population

48 children with severe obesity were consecutively recruited at our Outpatient Department of Paediatric Nutrition among patients evaluated for obesity. Severe obesity was defined as a body-mass-index Z score three or more SDs above the means specific for age and sex in normal French children.⁸ All the obese children were normotensive. Duration of obesity ranged from 2·7 to 15·2 years (median 9·1). Results in the obese patients were compared with those in 27 normotensive control children with

Results

The physical characteristics and lipid concentrations of the children are shown in table 1. Obese children had significantly higher concentrations of total cholesterol and triglycerides than controls, significantly lower HDL-cholesterol concentrations, and non-significantly higher LDL-cholesterol concentrations (table 1). Plasma apolipoproteins B (0·76 g/L [0·39–1·13]) and A-I (1·13 g/L [0·64–1·69]) were measured only in the obese children. The numbers of obese children with values above the

Discussion

Obesity in adolescence predicts a broad range of later health problems including an increased risk of cardiovascular morbidity and mortality.² Some of these late consequences, including cardiovascular disease, are independent of adult weight.³ Thus, permanent obesity-related abnormalities that increase the risk of coronary heart disease may occur in childhood. Consistent with this possibility, our study provided evidence that severe childhood obesity is associated with early endothelial

References (30)

WB Kannel
Metabolic risk factors for coronary heart disease in women: perspective from the Framingham study
Am Heart J
(1987)
SR Srinivasan et al.
Adolescent overweight is associated with adult overweight and related multiple cardiovascular risk factors: the Bogalusa Heart Study
Metabolism
(1996)
DJ Gunnell et al.
Childhood obesity and adult cardiovascular mortality: a 57-year follow-up study based on the Boyd Orr cohort
Am J Clin Nutr
(1998)
DS Celermajer et al.
Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis
Lancet
(1992)
PO Kwiterovich
Diagnosis and management of familial dyslipoproteinemia in children and adolescents
Pediatr Clin North Am
(1990)
JO Toikka et al.
Constantly low HDL-cholesterol concentration relates to endothelial dysfunction and increased in vivo LDL-oxidation in healthy young men
Atherosclerosis
(1999)
G Lebuffe et al.
Endothelial derived vasorelaxation is impaired in human apo A-I transgenic rabbits
Biochem Biophys Res Commun
(1997)
RA Markus et al.
Influence of lifestyle modification on atherosclerotic progression determined by ultrasonographic change in the common carotid intima-media thickness
Am J Clin Nutr
(1997)
S Owens et al.
Visceral adipose tissue and cardiovascular risk factors in obese children
J Pediatr
(1998)
M Mietus-Snyder et al.
Endothelial dysfunction occurs in children with two genetic hyperlipidemias: improvement with antioxidant vitamin therapy
J Pediatr
(1998)

A Must et al.

Long term morbidity and mortality of overweight adolescents: a follow-up of the Harvard Growth Study of 1922 to 1935

N Engl J Med

(1992)

Y Aggoun et al.

Arterial mechanical changes in children with familial hypercholesterolemia

Arteriosler Thromb Vasc Biol

(2000)

Y Aggoun et al.

Mechanical properties of the common carotid artery in Williams syndrome

Heart

(2000)

MF Rolland-Cachera et al.

Body mass index variations: centiles from birth to 87 years

Am J Clin Nutr

(1991)

SR Daniels et al.

Association of body fat distribution and cardiovascular risk factors in children and adolescents

Circulation

(1999)

Cited by (706)

Effects of childhood obesity on heart failure and its associated risk factors in the European population: A Mendelian randomization study
2024, Nutrition, Metabolism and Cardiovascular Diseases
Observational studies have shown that obesity considerably affects the cardiovascular system. Thus we conducted this Mendelian randomization (MR) analysis to evaluate the causal effect of childhood obesity on heart failure (HF) and its risk factors.
We obtained genetic instruments from genome-wide association studies (GWAS) that investigated childhood obesity, HF, type 2 diabetes mellitus (T2DM), atrial fibrillation (AF), coronary artery disease (CAD), myocardial infarction (MI), chronic kidney disease (CKD), valvular heart disease, myocarditis, hypertrophic cardiomyopathy, and hyperthyroidism. Inverse variance weighting (IVW), weighted median analysis, MR-Egger, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were employed for MR analyses. In addition, the leave-one-out sensitivity test, MR-PRESSO global test, and Cochran’s Q test were used for sensitivity analyses. Genetic evaluations showed that childhood obesity increases the risk of HF (odds ratio [OR] = 1.11, 95%CI: 1.05–1.17, p = 1.26 × 10⁻⁴), T2DM (OR = 1.17, 95%CI: 1.12–1.23, p = 8.80 × 10⁻¹²), AF (OR = 1.08, 95%CI: 1.05–1.12, p = 2.66 × 10⁻⁷), MI (OR = 1.08, 95%CI: 1.04–1.13, p = 3.35 × 10⁻⁴), and CAD (OR = 1.08, 95%CI: 1.03–1.13, p = 1.48 × 10⁻³). We found no association between childhood obesity and CKD, valvular heart disease, myocarditis, hypertrophic cardiomyopathy, or hyperthyroidism. Sensitivity analysis and Bonferroni’s correction showed consistent results.
Our study provides new evidence for the relationship between childhood obesity and HF and its risk factors. The results indicate that individuals with a history of childhood obesity require more clinical attention to prevent the development of HF.
The impact of lipopolysaccharide on cerebrovascular function and cognition resulting from obesity-induced gut dysbiosis
2024, Life Sciences
Obesity is a worldwide epidemic coinciding with a concomitant increase in the incidence of neurodegenerative diseases, particularly dementia. Obesity is characterised by increased adiposity, chronic low-grade systemic inflammation, and oxidative stress, which promote endothelial dysfunction. Endothelial dysfunction reduces cerebrovascular function leading to reduced cerebral blood flow and, eventually, cognitive decline, thus predisposing to a neurodegenerative disease. Obesity is also characterised by gut dysbiosis and a subsequent increase in the lipopolysaccharide which increasingly activates toll-like receptor 4 (TLR4) and further promotes chronic low-grade systemic inflammation. This also disrupts the crosstalk within the gut-brain axis, thus influencing the functions of the central nervous system, including cognition. However, the mechanisms by which obesity-related increases in oxidative stress, inflammation and endothelial dysfunction are driven by, or associated with, increased systemic lipopolysaccharide leading to reduced cerebrovascular function and cognition, beyond normal ageing, have not been elucidated. Hence, this review examines how increased concentrations of lipopolysaccharide and the subsequent increased TLR4 activation observed in obesity exacerbate the development of obesity-induced reductions in cerebrovascular function and cognition.
The effects of high-intensity interval training and moderate-intensity continuous training on visceral fat and carotid hemodynamics parameters in obese adults
2022, Journal of Exercise Science and Fitness
The present study aimed to examine the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on visceral fat and hemodynamic parameters in obese adults.
Fifty-two males were included in this study and divided into three groups: HIIT group (n = 21, age = 20.86 ± 1.62 years, BF (%) = 30.10 ± 5.02), MICT group (n = 22, age = 20.76 ± 1.14 years, BF (%) = 30.19 ± 5.76), and control group (CON) (n = 9, age = 21.38 ± 1.77 years, BF (%) = 30.40 ± 5.10). The HIIT and MICT groups received the exercise intervention three to four times per week for eight weeks (HIIT: exercise intensity 80–95% HRmax, circuit; MICT: exercise intensity 60–70% HRmax, running), and the control (CON) group received health education and guidance without exercise intervention. The body compositions and serum lipid indexes were tested to calculated LAP and VAI. The color doppler ultrasound diagnostic technology was used to test the artery diameter and blood velocity before and after the intervention. Based on the test data, MATLAB software and Womersley theory were used to calculate the hemodynamic parameters of the common carotid artery, including wall shear stress, flow rate, blood pressure, oscillatory shear index, elasticity modulus, dynamic resistance, artery diameter, arterial stiffness, circumferential strain and pulsatility index.
We found that lipid accumulation product (LAP) was significantly decreased in both the HIIT group (p < 0.01) and MICT (p < 0.05) group but not in the CON group (p > 0.05). In contrast, visceral adiposity index (VAI) decreased in both the HIIT and MICT groups and increased in the CON group, although the difference among groups was not significant (p > 0.05). After 8 weeks of intervention, the blood velocity and wall shear stress were greater after HIIT and MICT intervention (p < 0.01). Artery diameter, oscillatory shear index, arterial stiffness, and pulsatility index decreased significantly, and circumferential strain increased significantly in the HIIT group (all, p < 0.01, p < 0.05) but not in the MICT group (p > 0.05). Dynamic resistance was significantly decreased in the MICT group. There was no difference in the CON group after the period of intervention (all, p > 0.05). LAP was positively related to artery diameter (r = 0.48, p = 0.011), blood pressure (r = 0.46, p = 0.002), flow rate (r = 0.31, p = 0.04), oscillatory shear index (r = 0.44, p = 0.03), and elasticity modulus (r = 0.33, p = 0.029) but inversely related to circumferential strain (r = −0.36, p = 0.028). The VAI was also positively associated with artery diameter (r = 0.33, p = 0.03), elasticity modulus (r = 0.38, p = 0.009), and arterial stiffness (r = 0.39, p = 0.012). In addition, the VAI was negatively correlated with the circumferential strain (r = −0.33, p = 0.04).
The present study demonstrated that both HIIT and MICT exercises for 8 weeks could effectively enhance visceral fat indices and partial hemodynamic parameters. Therefore, HIIT and MICT exert important effects on reducing fat content and improving hemodynamic environment. But HIIT on oscillatory shear index, arterial stiffness, circumferential strain, and pulsatility index was superior to MICT. In addition, there are close correlations between visceral fat and partial hemodynamic parameters of the common carotid artery.
The 100 top-cited articles on childhood obesity: a bibliometric analysis
2022, Global Health Journal
Childhood obesity (CHO) is a serious global health challenge affecting both developed and developing nations. The feats attained in addressing this global health challenge can be reflected through the top-cited studies. The study's aim was to analyze the features of the 100 top-cited articles concerning CHO.
We used a bibliometric analysis, and searched for relevant articles from the Web of Science (December 1, 2021), using an appropriate keyword search-strategy ((child OR childhood OR children OR adolescent) AND (obese OR obesity OR overweight)). The retrieved documents were analysed based on the citation number, publication year, authorship, institution, journal and country. The analyses were performed mainly by the Bibliometrix application (using R-studio cloud) and HistCite.
The 100 top-cited articles were published between 1976 and 2018, their citations ranged from 365 to 10 789, with a mean citation of 1 146.2 and 31 studies had more than 1 000 citations. The articles were published in 31 journals, with the “Pediatrics” journal having the most publications (n = 18). The studies were from 12 countries, with the most-productive being the USA (n = 68), followed by the United Kingdom (n = 12) and France (n = 3). The leading institution was the University of Bristol (n = 8), while Dietz WH (n = 12), and Flegal KM (n = 8) were the most productive authors. The most common research fields covered by these articles were; “General Internal Medicine” (n = 34), “Pediatrics” (n = 29), and “Nutrition Dietetics” (n = 18). The study noted significant correlations between the total article citation and the number of authors (R = 0.203), countries involved (R = 0.407), institutions (R = 0.407), and the publication year (R = 0.847), all with P < 0.001.
Through these top-cited articles, this analysis provides discernment into the historical advancements, including the prime roles performed by various stakeholders in addressing the issue of CHO. However, Asian countries’ contribution is not adequately reflected in these articles, and thus more focus and funding for CHO research are needed for effectual prevention and control.
Arterial Stiffness and Carotid Intima-Media Thickness in Children Exposed to Smokeless Tobacco in Fetal Life
2024, Journal of the American Heart Association
Factors related to adolescent obesity and changes: a cross-sectional study based on the Korea Youth Risk Behavior Survey
2023, Korean Journal of Community Nutrition

View all citing articles on Scopus

View full text

ArticlesPresence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Study population

Results

Discussion

Am Heart J

Metabolism

Am J Clin Nutr

Lancet

Pediatr Clin North Am

Atherosclerosis

Biochem Biophys Res Commun

Am J Clin Nutr

J Pediatr

J Pediatr

Long term morbidity and mortality of overweight adolescents: a follow-up of the Harvard Growth Study of 1922 to 1935

N Engl J Med

Arterial mechanical changes in children with familial hypercholesterolemia

Arteriosler Thromb Vasc Biol

Mechanical properties of the common carotid artery in Williams syndrome

Heart

Body mass index variations: centiles from birth to 87 years

Am J Clin Nutr

Association of body fat distribution and cardiovascular risk factors in children and adolescents

Circulation

Articles
Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study