title: Statin therapy and secretory phospholipase A₂ in children with heterozygous familial hypercholesterolemia.
abstract: OBJECTIVE
  Secretory phospholipase A2 (sPLA2) enzymes are thought to contribute to atherosclerosis. In this study we assessed levels of sPLA2 mass and activity, and their relationship to baseline characteristics of children with familial hypercholesterolemia (FH). Furthermore, we evaluated the effect of two years of pravastatin therapy on sPLA2 levels.
  
  
  RESULTS
  sPLA2-IIA mass and sPLA2 activity were measured at baseline and after two years in 187 children with FH (aged 8-18 years) randomized to pravastatin or placebo. At baseline, median [IQR] sPLA2-IIA mass and sPLA2 activity levels were 7.2 [5.8-13.2] ng/ml and 36.4 [29.8-47.1] U/ml, respectively. Both sPLA2-IIA mass and sPLA2 activity were significantly correlated with high-sensitivity C-reactive protein (r = 0.33, p < 0.001 and r = 0.386, p < 0 .001, respectively), but not with other cardiovascular risk factors. Baseline levels of sPLA2-IIA mass and sPLA2 activity were not significantly associated with carotid intima-media thickness (cIMT) at baseline or at the end of follow-up. After two years, sPLA2-IIA mass and sPLA2 activity levels were not significantly reduced in the pravastatin group (p = 0.20 and p = 0.63, respectively), nor in the placebo group (p = 0.17 and p = 0.11, respectively). Changes from baseline did not differ between the treatment groups for sPLA2-IIA mass (p = 0.48) and sPLA2 activity (p = 0.88).
  
  
  CONCLUSIONS
  sPLA2-IIA mass and sPLA2 activity were not significantly associated with cIMT in our pediatric FH cohort. This could indicate that the potential predictive role of sPLA2 as a biomarker of cardiovascular disease in children with FH is limited. Treatment with pravastatin did not reduce sPLA2-IIA mass or sPLA2 activity levels, as compared to placebo. Further studies with larger samples are required to address these issues.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Marjet J A M
authors.initials: MJ
authors.lastname: Braamskamp
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tsimikas
authors.forename: Albert
authors.initials: A
authors.lastname: Wiegman
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Hutten
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D059168:Carotid Intima-Media Thickness; D002648:Child; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D054497:Phospholipases A2, Secretory / Q000097:blood*; D017035:Pravastatin / Q000008:administration & dosage*; D011237:Predictive Value of Tests
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein; D054497:Phospholipases A2, Secretory; D017035:Pravastatin
keywords: Familial hypercholesterolemia; Lipoproteins; Secretory phospholipase A(2); Statins