ASSOCIATION OF CIRCULATING ENDOTHELIAL CELLS AND ENDOTHELIAL PROGENITOR CELLS IN DYSLIPIDEMIC CHILDREN AND ADOLESCENTS

Abstract

Circulating endothelial progenitor cells (CEPCs) and endothelial cells (CECs) have been hypothesized to be an important etiologic and surrogate biologic marker for vascular dysfunction/damage and cumulative cardiovascular risk, but the direction of association may differ for children versus adults. For adults, lower CEPCs is felt to be a biomarker of increased CV risk and higher CECs a biomarker of vascular damage. n=134 children (52% males; mean age 11.7+3.3 years; mean LDL-C 4.29+1.79 mmol/L) were enrolled from a pediatric lipid disorders clinic, and had medical, lifestyle behavior (food records, accelerometry) and family history review, anthropometry, and assessment of blood pressure and fasting blood work. Flow cytometry separately identified and enumerated CD45 negative/CD31 positive/CD146 positive/VEGFR2 positive cells that were CD133 positive (CECs) and negative (CEPCs). Factors associated with CECs and with CEPCs were sought in linear regression models. Higher CECs was significantly associated with higher systolic blood pressure z-score (p=0.03), paternal hypertension (p=0.01), older age (p=0.02), higher weight (p=0.03), higher total (p=0.05), non-HDL (p=0.05) and LDL cholesterol (p=0.04), as well as higher hepatic transaminases (AST, p=0.04; ALT, p<0.001). Higher CEPCs was significantly associated with better nutritional score (p<0.001), higher waist circumference percentile (p=0.04) and systolic hypertension (p=0.03). n=23 patients were treated with rosuvastatin. The proportion of patients with CECs >0.10 cells/uL was 65% at baseline, and 91% after 12 and 89% after 24 months of statin (p=0.04). The proportion of patients with CEPCs >0 cells/uL was 35% at baseline, and 35% after 12 and 37% after 24 months of statin (p=NS). For children with dyslipidemia, higher CECs more so than CEPCs was associated with increased CV risk, and were paradoxically increased with treatment with statin. The relationship between CECs and CEPCs and CV risk may be more complex in pediatric patients.