Cardiovascular Risk Factors Evaluation in Children

RISK FACTORS FOR SUBCLINICAL ATHEROSCLEROSIS IN

ASYMPTOMATIC BRAZILIAN CHILDREN.

REFERENCES

1. Beauloye V, Zech F, Mong HTT, Clapuyt P, Maes M, Brichard SM (2007) Determinants

of early atherosclerosis in obese children and adolescents. J Clin Endocrin Metab 92:

3025-3032

2. Berenson GS, Srinivasan SR, Bao W, Newman WP 3rd, Tracy RE, Wattigney WA

(1998) Association between multiple cardiovascular risk factors and atherosclerosis in

children and young adults. The Bogalusa Heart Study. N Engl J Med 338: 1650-1656

3. Berenson GS (2002) Childhood risk factors predict adult risk associated with subclinical

cardiovascular disease. The Bogalusa Heart Study. Am J Cardiol 90 (suppl.): 3L-7L

4. Cole TJ, Bellizi MC, Flegal KM, Dietz WH (2000) Establishing a standard definition for

child overweight and obesity worldwide: international survey. BMJ 320: 1240-1243

5. Conde WL, Monteiro CA (2006) Body mass index cutoff points for evaluation of

nutritional status in Brazilian children and adolescents. J Pediatr (Rio J) 82: 266-272

6. Cuomo S, Guarini P, Gaeta G, De Michele M, Boeri F, Dorn J, Bond M, Trevisan M

(2002) Increased carotid intima-media thickness in children-adolescents, and young

adults with a parental history of premature myocardial infarction. Eur Heart J 23: 1345-

1350 2

7. Executive Summary of the Third Report of the National Cholesterol Education Program

(NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood

Cholesterol in Adults (Adult Treatment Panel III) (2001) JAMA 285: 2486-2508

8. Fox CS, Polak JF, Chazaro I, Cupples A, Wolf PA, D'Agostino RA, O'Donnell CJ (2003)

Genetic and environmental contributions to atherosclerosis phenotypes in men and

women: heritability of carotid intima-media thickness in the Framingham Heart Study.

Stroke 34: 397-401

9. Freedman DS, Dietz WH, Tang R, Mensah GA, Bond MG, Urbina EM, Srinivasan S,

Berenson GS (2004) The relation of obesity throughout life to carotid intima-media

thickness in adulthood: The Bogalusa Heart Study. Int J Obes Metab Disord 28: 159-166

10. Freedman DS, Patel DA, Srinivasan SR, Chen W, Tang R, Bond MG, Berenson GS

(2008) The contribution of childhood obesity to adult carotid intima-media thickness: the

Bogalusa Heart Study. Int J Obes 32: 749-756

11. Ishizu T, Ishimitsu T, Yanagi H, Obara K, Moriyama N, Watanabe S, Yamaguchi I.

(2004) Effect of age on carotid arterial intima-media thickness in childhood. Heart

Vessels 19: 189-195

12. Juonala M, Raitakari M, Viikari JSA, Raitakari OT (2006) Obesity in youth is not an

independent predictor of carotid IMT in adulthood. The Cardiovascular Risk in Young

Finns Study. Atherosclerosis 185: 388-393

13. Juonala M, Viikari JSA, Räsänen L, Helenius H, Pietikäinen M, Raitakari OT (2006)

Young adults with family history of coronary heart disease have increased arterial

vulnerability to metabolic risk factors. The Cardiovascular Risk in Young Finns Study.

Arterioscler Thromb Vasc Biol 26: 1376-1382 3

14. Kavey RE, Alada V, Daniels SR, Hayman LL, McCrindle BW, Newburger JW, Parekh

RS, Steinberger J (2006) Cardiovascular risk reduction in high-risk pediatric patients: a

scientific statement from the American Heart Association Expert Panel on Population and

Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology

and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure

Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the

Interdisciplinary Working Group on Quality of Care and Outcomes Research. Circulation

114: 2710-2738

15. Li S, Chen W, Srinivasan SR, Tang R, Urbina EM, Berenson GS (2003) Childhood

cardiovascular risk factors and carotid vascular changes in adulthood. The Bogalusa Heart

Study. JAMA 290: 2271-2276

16. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M (2007) Prediction of clinical

cardiovascular events with carotid intima-media thickness. A systematic review and

meta-analysis. Circulation 115: 459-467

17. Lusis AJ (. 2000) Atherosclerosis. Nature 407: 233-241

18. Must A, Jacques PJ, Dallal GE, Bajema CJ, Dietz WH (1992) 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

19. O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr (1999)

Carotid-artery intima and media thickness as a risk factor for myocardial infarction and

stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N

Engl J Med 340: 14-22 4

20. 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 (1990) JAMA 264: 3018-3024

21. Stary HC (1989) Evolution and progression of atherosclerotic lesions in coronary arteries

of children and young adults. Arteriosclerosis 9 (Suppl 1): I19-I32

22. Tonstad S, Joakimsen O, Stensland-Bugge E, Leren TP, Ose L, Russell D, Bønaa KH

(1996) 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

23. Update on the 1987 Task Force Report on High Blood Pressure in Children and

Adolescents: a working group report from the National High Blood Pressure Education

Program. National High Blood Pressure Education Program Working Group on

Hypertension Control in Children and Adolescents (1996) Pediatrics 98: 649-658

24. Vicenzini E, Ricciardi MC, Puccinelli F, Guidetti G, Delfini R, Lenzi GL (2007)

Common carotid artery intima-media thickness determinants in a population study. J

Ultrsound Med 26: 427-432

25. World Health Organization. BMI-for-age (5-19 years).

http://www.who.int/growthref/who2007_bmi_for_age/en/print.html. Assessed May 2,

26. Wunsch R, de Souza G, Toschke AM, Reinehr T (2006) Intima-media thickness in obese

children before and after weight loss. Pediatrics 118: 2334-2340 5

TABLES

Table 1: Anthropometric, clinical and laboratory characteristics of the study population. Normal weight Overweight and Variable Total (n=93) (n=52) obese (n=41) Age (months): mean (±SD) 106 (±29) 104 (±28) 109 (±30) Caucasian: n (%) 78 (84) 43 (83) 35 (85) Male: n (%) 49 (53) 27 (52) 22 (54) BMI (kg/m2): mean (±SD) 18.9 (±5.1) 15.6 (±1.7)* 22.7 (±5.1)* Family history of CHD: n (%) 55 (60) 29 (56) 26 (63) DBP (mm Hg): mean (±SD) 68 (±10) 66 (±10) 70 (±10) SBP (mm Hg): mean (±SD) 109 (±14) 107 (±15) 109 (±12) Composite cIMT (mm): mean (±SD) 0.44 (±0.07) 0.43 (±0.06)** 0.46 (±0.08)** Fibrinogen (mol/l): mean (±SD) 8.40 (±2.06) 7.97 (±2.03) 8.76 (±2.03) Glucose (mmol/l): mean (±SD) 4.61 (±0.40) 4.60 (±0.37) 4.62 (±0.45) HDL (mmol/l): mean (±SD) 1.37 (±0.40) 1.42 (±0.34) 1.29 (±0.26) LDL (mmol/l): mean (±SD) 2.32 (±0.74) 2.28 (±0.83) 2.56 (±0.67) T-CHOL (mmol/l): mean (±SD) 4.11 (±1.16) 4.09 (±1.14) 4.22 (±0.78) Triglycerides (mmol/l): median (IQR) 0.76 (0.55–1.03) 0.67 (0.47-0.87)# 0.89 (0.80-1.02)# SD: standard deviation; BMI: body mass index; CHD: cardiovascular heart disease; DBP: diastolic blood pressure; SBP: systolic blood pressure; HDL: high-density lipoprotein cholesterol;

LDL: low-density lipoprotein cholesterol; T-CHOL: total cholesterol; IQR: interquartile range; cIMT: carotid intima-media thickness; * and **: Student’s t test - P<0.001 and P=0.023, respectively; #: Mann-Whitney test; P=0.010. 6

Table 2: Pearson’s correlation coefficients for normally distributed variables (P value); n=93. Age Glucose Fibrinogen DBP SBP BMI z-score Composite cIMT Age 1.0 0.200 - 0.102 - 0.020 - 0.014 0.001 0.132 (0.054) (0.331) (0.850) (0.895) (0.995) (0.206)

Glucose 0.200 1.0 0.051 0.001 0.126 0.151 0.113 (0.054) (0.150) (0.999) (0.227) (0.150) (0.279)

Fibrinogen - 0.102 0.051 1.0 0.008 0.092 0.254 0.082 (0.331) (0.150) (0.938) (0.383) (0.014) (0.433)

DBP - 0.020 0.001 0.008 1.0 0.772 0.301 0.107 (0.850) (0.999) (0.938) (<0.001) (0.003) (0.307)

SBP - 0.014 0.126 0.092 0.772 1.0 0.296 0.256 (0.895) (0.227) (0.383) (<0.001) (0.004) (0.013)

BMI z-score 0.001 0.151 0.254 0.301 0.296 1.0 0.259 (0.995) (0.150) (0.014) (0.003) (0.004) (0.012) 0.259 Composite cIMT 0.132 0.113 0.082 0.107 0.256 1.0 (0.206) (0.279) (0.433 (0.307 (0.013) (0.012) DBP: diastolic blood pressure; SBP: systolic blood pressure. 7

Table 3: Spearman’s correlation coefficients for categorical of skewed variables (P value); n=93. Gender CHD CRP T-CHOL HDL TGL Overweight Composite Obesity cIMT 0.045 - 0.062 -0.129 -0.129 - 0.059 Gender 1.0 0.047 0.193 (0.670) (0.554) (0.226) (0.219) (0.572) (0.655) (0.063) 0.045 0.231 - 0.135 - 0.068 - 0.141 0.082 - 0.043 CHD 1.0 (0.670) (0.026) (0.206) (0.521) (0.178) (0.435) (0.681) - 0.062 0.231 0.098 - 0.094 - 0.068 0.027 0.113 CRP 1.0 (0.554) (0.023) (0.360) (0.371) (0.519) (0.800) (0.280) -0.129 - 0.135 0.098 0.251 0.468 0.087 0.060 T-CHOL* 1.0 (0.226) (0.206)) (0.360) (0.018) (<0.001) (0.414) (0.573) -0.129 - 0.068 - 0.094 0.251 - 0.010 - 0.249 - 0.029 HDL* 1.0 (0.219) (0.521)) (0.371) (0.018) (0.927) (0.017) (0.784) - 0.059 - 0.141 - 0.068 0.468 - 0.010 0.297 0.043 TGL 1.0 (0.572) (0.178) (0.519) (<0.001) (0.927) (0.004) (0.682) Overweight/ 0.047 0.082 0.027 0.087 - 0.249 0.297 0.230 1.0 obesity (0.655) (0.435)) (0.800) (0.414) (0.017) (0.004) (0.027) Composite 0.193 - 0.043 0.113 0.060 - 0.029 0.043 0.230 1.0 cIMT (0.063) (0.681)) (0.280) (0.573) (0.784) (0.682) (0.027)

CHD: coronary heart disease; CRP: C-reactive protein; T-CHOL: total cholesterol;

HDL: high-density lipoprotein cholesterol; TGL: triglycerides.