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Brief Report

Increased Carotid Intima-Media Thickness and Stiffness in Obese Children

  1. Arcangelo Iannuzzi, MD1,
  2. Maria Rosaria Licenziati, MD2,
  3. Ciro Acampora, MD3,
  4. Vittorio Salvatore, MD1,
  5. Lucia Auriemma2,
  6. Maria Luigia Romano, MD3,
  7. Salvatore Panico, MD4,
  8. Paolo Rubba, MD4 and
  9. Maurizio Trevisan, MD5
  1. 1Department of Medicine, Cava de’ Tirreni Hospital, Salerno, Italy
  2. 2Department of Pediatrics, A. Cardarelli Hospital, Naples, Italy
  3. 3Department of Radiology, A. Cardarelli Hospital, Naples, Italy
  4. 4Department of Clinical and Experimental Medicine, School of Medicine, Federico II University, Naples, Italy
  5. 5Department of Social and Preventive Medicine, School of Public Health and Health Professions, State University of New York, Buffalo, New York
  1. Address correspondence and reprint requests to Dr. Arcangelo Iannuzzi, MD, Cava de’ Tirreni Hospital, Department of Medicine, Via de Marinis, SS18, 84013 Cava de’ Tirreni, Salerno, Italy. E-mail: lelliann{at}libero.it
Diabetes Care 2004 Oct; 27(10): 2506-2508. https://doi.org/10.2337/diacare.27.10.2506
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  • HOMA, homeostasis model assessment
  • IMT, intima-media thickness

Obesity in childhood increases the risk of atherosclerotic disease and death in adulthood (1). A dramatic increase in overweight among children and adolescents during the past 2 decades has been documented (2). Moreover, overweight children and adolescents have an increased risk of adult obesity (3). A clustering of factors typical of the insulin resistance syndrome has been identified in 5- to 10-year-old overweight/obese African-American children (4) and in preadolescent obese children (5). The pediatric obesity epidemic accounts for most new diagnoses of type 2 diabetes, a disease once virtually confined to adulthood, in adolescence (6).

High-resolution B-mode ultrasound measurements of carotid intima-media thickness (IMT) and stiffness are markers of early, preclinical atherosclerosis. Previous observations show significantly increased IMT in familial hypercholesterolemic children (7,8) and in children with type 1 diabetes (9) and hypertension (10). Recent evidence suggests an increased arterial stiffness in familial hypercholesterolemic children (11) and in children with severe obesity (12).

However, in the study by Tounian et al. (12) there was no evidence of statistically significant differences in carotid IMT between severely obese children and control subjects; moreover, there was no subgroup analyses for boys versus girls. The present study aimed to verify whether obesity in childhood may cause premature vascular alterations in both sexes.

RESEARCH DESIGN AND METHODS

We studied 100 children with obesity consecutively recruited from the outpatient clinic of the Department of Pediatrics, A. Cardarelli Hospital, Naples, Italy, among patients evaluated for overweight or obesity and 47 healthy age-matched control subjects. The inclusion criteria for both obese children and control subjects were age 6–14 years; no personal history of diabetes or impaired fasting glucose, hypercholesterolemia, or hypertension; absence of any pharmacological therapy; and absence of cardiovascular disease in their parents. Obesity was defined as BMI >95th percentile of the reference values stated in the Centers for Disease Control and Prevention growth chart (13).

All of the children had measurements of fasting serum total cholesterol, triglycerides, apolipoproteins A and B, HDL cholesterol, plasma glucose and insulin, C-reactive protein, and glycated HbA1c. An oral glucose tolerance test was performed in the obese children. The estimate of insulin resistance was calculated by a homeostasis model assessment (HOMA) score, as described by Matthews et al. (14). Quantitative B-mode ultrasound measurements of common carotid IMT and stiffness were calculated for all children following a standardized protocol. Carotid stiffness was calculated using the following formula: β = (natural logarithm systolic blood pressure − natural logarithm diastolic blood pressure)/(systolic diameter − diastolic diameter)/diastolic diameter.

Statistical analysis

Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS 11). Univariate, unadjusted analyses between obese and control subjects were performed with the independent samples t test. Stiffness measures were not normally distributed, and a Kruskal-Wallis test was used. ANCOVA was used to evaluate the presence of confounding variables in the relationship between obesity status and vascular parameters. Models were adjusted for several confounding variables, including age, sex, systolic blood pressure, total cholesterol, HDL cholesterol, and triglycerides. Adjusted means and CIs were estimated with the use of the Bonferroni method. The coefficient of variation for each pair of IMT and diameter measurements was 3.9% for IMT measurements, 1.8% for lumen systolic diameters, and 2.5% for lumen diastolic diameters.

RESULTS

Table 1 shows anthropometrical, biochemical, and ultrasonic parameters of the arterial carotid wall in obese and nonobese children. Obese children had significantly higher blood pressure and plasma concentrations of triglycerides, cholesterol, glucose, insulin, HOMA, and C-reactive protein than control subjects. Carotid thickness and stiffness were significantly different between obese and nonobese children and in both boys and girls.

For carotid IMT, when we added traditional cardiovascular risk factors (except for blood pressure and HOMA) in addition to age and sex as covariates, we still found evidence of statistically significant differences between obese children and control subjects. IMT in obese children was 0.55 mm (95% CI 0.54–0.57) and in healthy control subjects was 0.48 mm (0.46–0.51, P = 0.001). The further addition of C-reactive protein did not materially modify the outcome of our analyses. Adding systolic blood pressure as a covariate reduced the P value, but the statistical significance was retained. However, when glucose level was substituted by HOMA, the statistical significance was further reduced to a level that did not reach the formal level of statistical significance. IMT in obese children was 0.54 mm (0.52–0.56), and IMT in healthy control subjects was 0.51 mm (0.48–0.54, P = 0.099).

CONCLUSIONS

Obese children have significantly increased carotid IMT and stiffness compared with healthy control children. A previous study demonstrated an increased stiffness of the carotid artery in obese children (12) (a finding confirmed in the present study) but concluded that no significant difference was present in IMT between obese and nonobese children. The apparent discrepancy with the present observation could be due to the limited statistical power available for the study by Tounian et al. (12), which focuses on much smaller sample sizes (48 obese children and 27 control subjects). Increased carotid IMT and stiffness in obese boys and girls could reflect structural changes of large arteries that occur very early in atherosclerosis. The increased vascular IMT and stiffness in obese children compared with healthy control subjects suggests that obesity in children represents a powerful determinant of early manifestations of atherosclerosis and affects structural and mechanical properties of major vessels. The effect on structural changes appears to be mediated, at least in part, by the risk factors considered, especially systolic blood pressure and, most importantly, insulin resistance. Based on these findings, children affected by the insulin resistance syndrome are at particularly higher risk of developing premature cardiovascular complications. Our observation confirms that obesity and its associated comorbidities, particularly hypertension and insulin resistance, even in this young age should be regarded as a disease with vascular implications. We emphasize that weight reduction and risk-factor control in obese children for the long-term prevention of atherosclerosis and its sequelae should begin in childhood.

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Table 1—

Physical characteristics and biochemical and ultrasonographic parameters

Footnotes

  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    • Accepted June 30, 2004.
    • Received May 15, 2004.
  • DIABETES CARE

References

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    Must A, Jacques PF, Dallal GE, Bajema CJ, Dietz WH: Long-term morbidity and mortality of overweight adolescents: a follow-up of the Harvard Growth Study of 1922 to 1935. N Engl J Med 327:1350–1355, 1992
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    Freedman DS, Srinivasan SR, Valdez RA, Williamson DF, Berenson GS: Secular increases in relative weight and adiposity among children over two decades: the Bogalusa Heart Study. Pediatrics 99:420–426, 1997
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    Serdula MK, Ivery D, Coates RJ, Freedman DS, Williamson DF, Byers T: Do obese children become obese adults? A review of literature. Prev Med 22:167–177, 1993
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    Young-Hyman D, Schlundt DG, Herman L, De Luca F, Counts D: Evaluation of the insulin resistance syndrome in 5- to 10-year-old overweight/obese African-American children. Diabetes Care 24:1359–1364, 2001
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    Caprio S, Bronson M, Sherwin RS, Rife F, Tamborlane WV: Coexistence of severe insulin resistance and hyperinsulinaemia in pre-adolescent obese children. Diabetologia 39:1489–1497, 1996
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    Ludwig DS, Ebbeling CB: Type 2 diabetes mellitus in children: primary care and public health considerations. JAMA 286:1427–1430, 2001
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    Pauciullo P, Iannuzzi A, Sartorio R, Irace C, Covetti G, Di Costanzo A, Rubba P: Increased intima-media thickness of the common carotid artery in hypercholesterolemic children. Arterioscler Thromb 14:1075–1079, 1994
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    Tonstad S, Joakimsen O, Stensland-Bugge E, Leren TP, Ose L, Russell D, Bonaa KH: Risk factors related to carotid intima-media thickness and plaque in children with familial hypercholesterolemia and control subjects. Arterioscler Thromb Vasc Biol 16:984–991, 1996
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    Jarvisalo MJ, Jartti L, Nanto-Salonen K, Irjala K, Ronnemaa T, Hartiala JJ, Celermajer DS, Raitakari OT: Increased aortic intima-media thickness: a marker of preclinical atherosclerosis in high-risk children. Circulation 104:2943–2947, 2001
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    Sorof JM, Alexandrov AV, Cardwell G, Portman RJ: Carotid artery IMT and LVH in children with elevated blood pressure. Pediatrics 111:61–66, 2003
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    Aggoun Y, Bonnet D, Sidi D, Girardet JP, Brucker E, Polak M, Safar ME, Levy BI: Arterial mechanical changes in children with familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 20:2070–2075, 2000
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    Tounian P, Aggoun Y, Dubem B, Varille V, Guy-Grand B, Sidi D, Girardet JP, Bonnet D: Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study. Lancet 358:1400–1404, 2001
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    Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, Wei R, Curtin LR, Roche AF, Johnson CL: 2000 CDC growth charts for the United States: methods and development. Vital Health Stat 11:1–190, 2002
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Increased Carotid Intima-Media Thickness and Stiffness in Obese Children
Arcangelo Iannuzzi, Maria Rosaria Licenziati, Ciro Acampora, Vittorio Salvatore, Lucia Auriemma, Maria Luigia Romano, Salvatore Panico, Paolo Rubba, Maurizio Trevisan
Diabetes Care Oct 2004, 27 (10) 2506-2508; DOI: 10.2337/diacare.27.10.2506

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Increased Carotid Intima-Media Thickness and Stiffness in Obese Children
Arcangelo Iannuzzi, Maria Rosaria Licenziati, Ciro Acampora, Vittorio Salvatore, Lucia Auriemma, Maria Luigia Romano, Salvatore Panico, Paolo Rubba, Maurizio Trevisan
Diabetes Care Oct 2004, 27 (10) 2506-2508; DOI: 10.2337/diacare.27.10.2506
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