Abstract 14013: Lipoprotein-Associated Phospholipase A2 Mass and Activity in Children with Heterozygous Familial Hypercholesterolemia: Effect of Pravastatin and Relationship to Carotid Intima Media Thickness
Background: Lipoprotein associated phospholipase A2 (Lp-PLA2) is an independent risk factor of cardiovascular disease and a target of treatment. The effect of statin therapy on Lp-PLA2 mass and activity in children with familial hypercholesterolemia (FH) is not known.
Methods: In a prior randomized trial, pravastatin was shown to significantly lower LDL cholesterol (LDL-C) and reduce the progression of carotid intima-media thickness (cIMT) in children aged 8–18 years with heterozygous FH. In this substudy, Lp-PLA2 mass and activity levels were measured at baseline and after 2 years in 179 children with FH randomized to pravastatin or placebo and in 78 unaffected and untreated siblings and correlated with changes in cIMT over 4 years of follow-up.
Results: Baseline levels of Lp-PLA2 mass and activity were significantly higher in children with FH compared to unaffected siblings. (Mass: 239.5±39.9, 241.3±43.4, and 221.1±36.5 ng/dl, p=0.002, activity: 204.5±36.5, 207.0±41.7, and 124.3±23.0 nmol/min/ml, p<0.0001 in each FH pravastatin, placebo, and unaffected siblings) After 2 years treatment, Lp-PLA2 mass (217.8±35.0 versus 231.5±34.6 ng/mL, mean difference between two groups: −12.2 ng/mL, P=0.001) and activity (178.8±37.3 versus 206.0±33.4 nmol/min/mL, mean difference between two groups: −26.5 nmol/min/mL, P<0.0001) were significantly lower in the pravastatin group compared to placebo. Change of Lp-PLA2 activity was related to change of LDL-C, (pravastatin: correlation coefficienct(r)=0.53, p<0.0001, placebo :r= 0.23,p<0.05) but not in change of Lp-PLA2 mass. (pravastatin: r=0.11, p=0.32, placebo :r= 0.05, p=0.65) In FH children, baseline Lp-PLA2 mass was an independent predictor of cIMT at a minimal follow-up of 4 years after statin treatment (p=0.036) after adjustment for duration of statin therapy, age and gender.
Conclusions: Lp-PLA2 mass and activity are significantly elevated in children with heterozygous FH compared to unaffected siblings and are significantly reduced by pravastatin. Change of Lp-PLA2 mass was not related to change of LDL-C. Baseline Lp-PLA2 mass is an independent predictor of the 4-year change in cIMT.
- © 2010 by American Heart Association, Inc.