Association between arterial stiffness and cardiovascular risk factors in a pediatric population

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+ Association between arterial stiffness and cardiovascular risk factors in a pediatric population Maria Perticone Department of Experimental and Clinical Medicine University Magna Graecia of Catanzaro ITALY

+ Background CVD is a big health problem and one of the leading cause of morbidity and mortality worldwide Most of the clinical manifestations of CVD appears in adulthood, even if risk factors for CVD may appear in childhood and adolescence 1 CV risk factors (obesity, dyslipidemia, high blood pressure, etc) are significantly correlated with adults levels over long term follow-up 2,3 In particular, in the last 30 yrs, the worldwide prevalence of obesity in childhood registered a great increase 4 12 Freedman DS, et al. Pediatrics 1999;103:1175-1182 3 Juhola J, et al. J Pediatr 2011;159:584-590 4 Ebbeling CB, et al. Lancet 2000;360:473-482

+ Definitions and measurement of CV risk factors in children Prediabetes/dia betes Prediabetes: FPG >100 mg/dl and <126 mg/dl Diabetes: FPG>126 mg/dl Pre-hypertension: BP 90 and < 95 Hypertension: BP 95 Arterial hypertension CVD Dyslipidemia Hypercholesterolemia: LDL 160 mg/dl and/or HDL<40 mg/dl Hypertriglyceridemia Triglycerides>200 mg/dl Overweight/ obesity Overweight: body weigth 85 and < 95 Obesity: body weigth 95

+ The endothelium LDL-c Hypertension Diabetes Smoking Oxidative stress Altered vasomotor tone Pro-thrombotic state Endothelial dysfunction Pro-inflammatory state Arterial wall proliferation Atherosclerosis

+ Arterial stiffness Arterial stiffness reflects the structural arterial wall modifications, characterizing vascular aging Abnormal arterial stiffness is an independent predictor for various adverse outcomes, including CVD, stroke, and renal disease. Arterial stiffness is associated with traditional CV risk factors and metabolic alterations including obesity, impaired glucose tolerance, and dyslipidemia It can be easily evaluated through pulse wave velocity (PWV) measurement

+ Aim of the study To evaluate the possible relationship between PWV and different CV risk factors (obesity, arterial hypertension, dyslipidemia, diabetes, hyperuricemia) in a group of pediatric subjects

+ Materials and methods We enrolled 69 subjects (31 M and 38 F; mean age 10+4 yrs) with at least 1 CV risk factor referred to our Department for the study of vascular function The study was approved by the Local Ethic Committee and written informed consent was obtained from parents/legal tutors of the subjects All subjects underwent collection of their medical history, physical examination, routine blood tests, insulinemia and HOMA index to evaluate insulin resistance

+ Vascular assessment Intima-media thickness was evaluated in all subjects through an ultrasound technique using 17MHz probe Pulse wave velocity was evaluated by a validated system employing high-fidelity applanation tonometry

+ Results Anthropometric and biochemical characteristics of the study population Variable Study population (n=69) Sex (M/F) 31/38 Age (yrs) 10.0+4.0 BMI (kg/m 2 ) 26.4+2.7 Total cholesterol (mg/dl) 170.4+39.0 HDL-cholesterol (mg/dl) 53.5+12.0 LDL-cholesterol (mg/dl) 98.7+31.1 Triglyceride 91.0+72.5 FPG (mg/dl) 84.9+8.8 Insulin (mu/l) 12.2+8.4 HOMA 2.62+1.89 hs-crp (mg/l) 0.42+0.21 Uric acid (mg/dl) 4.2+1.2

+ Results Hemodynamic characteristics of the study population Variable Study population (n=69) SBP (mmhg) 112.4+12.8 DBP (mmhg) 68.1+9.5 PP(mmHg) 43.6+9.2 c-sbp (mmhg) 101.1+13.5 c-dbp (mmhg) 70.6+9.6 c-pp (mmhg) 30.5+11.4 PWV (m/s) 4.8+0.8 AIx (%) 5.76+7.54

+ Results Linear regression analysis between PWV and different covariates r P HOMA 0.385 0.001 BMI (kg/m 2 ) 0.338 0.002 SBP (mmhg) 0.338 0.002 Uric acid (mg/dl) 0.241 0.023

PWV, m/sec PWV, m/sec PWV, m/sec PWV, m/sec + 9 R² = 0.1581 9 R² = 0.1224 6 6 3 3 0 0 2 4 6 8 HOMA 0 0.0 10.0 20.0 30.0 40.0 BMI, Kg/m 2 9 R² = 0.0619 9 R² = 0.1286 6 6 3 3 0 0 5 10 0 0 100 200 URIC ACID, mg/dl SBP, mmhg

+ Conclusions In our population PWV, a surrogate marker of arterial stiffness, resulted linearly related to all classical CV risk factors, similarly to what observed in adults In particular, we found a significant relationship between PWV and HOMA, BMI, SBP, and uric acid IR resulted the strongest independent predictor of PWV The early detection of CV risk factors in childhood is mandatory in order to promote corrective strategies