Lipoprotein-associated phospholipase A2: a new marker to determine cardiovascular risk in hypercholesterolemic dyslipidaemic children

Abstract

Background Inflammation and hypercholesterolaemia contribute to atherosclerotic changes which can start in childhood. Children with hyperlipidaemias are at high risk for early coronary atherosclerosis. This study evaluates the relationship between lipoprotein-associated phospholipase A₂ (Lp-PLA₂), carotid intima-media thickness (CIMT) and flow-mediated dilatation in hypercholesterolaemic dyslipidaemic children. Methods We performed a case-control study consisting of 43 cases, aged 2 to 17 years, and 24 age-matched controls. Fasting blood samples were obtained from both groups for the measurement of a lipid profile (total cholesterol, LDL-C, HDL-C and triglycerides) and Lp-PLA₂ in mass units. The latter was determined with a turbidimetric immunoassay method (PlacTest, DiaDexus Inc.) applied to an automated analyser. CIMT and flow-mediated dilatation measurements were undertaken by a paediatric cardiologist, using high-resolution B-mode ultrasonography. Results Total cholesterol, LDL-C and Lp-PLA₂ concentrations were significantly higher in the cases than in the controls ( p < 0.001 for all three parameters). While CIMT values were also significantly higher in the patients compared to the controls ( P = 0.001), flow-mediated dilatation values were significantly lower ( P = 0.001). We found positive correlations between Lp-PLA₂ and total cholesterol ( r = 0.41, P = 0.001), Lp-PLA₂ and LDL-C ( r = 0.36, P = 0.004), Lp-PLA₂ and CIMT ( r = 0.44, P = 0.019) and LDL-C and CIMT ( r = 0.41, P = 0.032); there were negative correlations between Lp-PLA₂ and flow-mediated dilatation ( r = -0.15, P = 0.045), total cholesterol and flow-mediated dilatation ( r = -0.45, P = 0.017), LDL-C and flow-mediated dilatation ( r = -0.51, P = 0.006) and CIMT and flow-mediated dilatation ( r = -0.45, P = 0.016). Conclusion Lp-PLA₂ concentrations are significantly elevated in hypercholesterolaemic dyslipidaemic children. Given the association of Lp-PLA₂ with markers of atherosclerosis (total cholesterol, LDL-C, CIMT and flow-mediated dilatation), the finding of increased concentrations of Lp-PLA₂ could be used to identify early atherosclerotic changes in hypercholesterolaemic dyslipidaemic children and may inform their clinical management.

Keywords: Hypercholesterolaemia; atherosclerosis; carotid intima-media thickness; children; flow-mediated dilatation; hyperlipidaemia; lipoprotein-associated phospholipase A2.