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 A (Lp-PLA), 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-PLA 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-PLA 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-PLA and total cholesterol ( r = 0.41, P = 0.001), Lp-PLA and LDL-C ( r = 0.36, P = 0.004), Lp-PLA 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-PLA 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-PLA concentrations are significantly elevated in hypercholesterolaemic dyslipidaemic children. Given the association of Lp-PLA with markers of atherosclerosis (total cholesterol, LDL-C, CIMT and flow-mediated dilatation), the finding of increased concentrations of Lp-PLA could be used to identify early atherosclerotic changes in hypercholesterolaemic dyslipidaemic children and may inform their clinical management.

Macrophages and Phospholipases at the Intersection between Inflammation and the Pathogenesis of HIV-1 Infection

“…This enzyme hydrolyzes the sn-2 acyl-chain of the phospholipid substrate on LDL surface releasing LPC and oxidized FFA, which concentrate in the sub-intimal space contributing to the development of foam cells and plaque lipid core [ 59 ]. In virtue of the important pro-atherogenic features of these metabolites, the measurement of Lp-PLA 2 activity was included among the biomarkers used in clinical practice for the stratification of adult asymptomatic patients at intermediate or high cardiovascular risk [ 54 ], and was recently proposed as a new marker to identify early atherosclerotic changes in hypercholesterolemic dyslipidemic children [ 60 ].…”

Endothelial Dysfunction in Children With Obstructive Sleep Apnea Is Associated With Elevated Lipoprotein‐Associated Phospholipase A2 Plasma Activity Levels

“…Lipoprotein‐associated phospholipase A2 (Lp‐PLA2) is a calcium‐independent lipase primarily produced by monocytes and macrophages that catalyzes the hydrolysis of the sn‐2 acyl chain of the phospholipid substrates on the surface of low‐density lipoproteins, releasing lysophosphatidylcholine and oxidized fatty acids . Lp‐PLA2 is recognized as an independent risk factor for cardiovascular disease (CVD) and atheromatous plaque activity in the general population, and elevations of Lp‐PLA2 have also been reported in children at significant CVD risk, including obese children . However, the impact of OSA on Lp‐PLA2 activity has not been examined to date and could constitute a potential indicator for CVD risk in this patient population.…”