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Lipoprotein-associated phospholipase A(2) mass and activity in children with heterozygous familial hypercholesterolemia and unaffected siblings: Effect of pravastatin

By Sung Kee Ryu, Barbara A. Hutten, Maud N. Vissers, Albert Wiegman, John J. P. Kastelein and Sotirios Tsimikas

Abstract

BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an independent risk factor of cardiovascular disease and a target of treatment. Lp-PLA(2) levels in children have not been previously reported. The effect of statin therapy on Lp-PLA(2) mass and activity in children with familial hypercholesterolemia (FH) is also not known. METHODS: Lp-PLA(2) mass and activity levels were measured at baseline and after 2 years in 178 children with FH randomized to pravastatin or placebo and in 78 unaffected and untreated siblings. At the end of the randomized period, all FH children were then placed on pravastatin for an additional 2 years, and Lp-PLA(2) mass and activity levels were correlated with changes in carotid intima-media thickness during 4 years of follow-up. RESULTS: Baseline levels of Lp-PLA(2) mass and activity were significantly greater in children with FH compared with unaffected siblings (mass: 240.3 +/- 41.6 vs 222.1 +/- 36.5 ng/mL, P = .002; activity: 205.7 +/- 41.6 vs 124.3 +/- 23.0 nmol/min/mL, P <.0001). In the randomized FH cohort, after 2 years treatment, Lp-PLA(2) mass (217.8 +/- 35.0 vs 231.5 +/- 34.8 ng/mL, P = .001) and activity (178.8 +/- 37.3 vs 206.2 +/- 33.5 nmol/min/mL, P <.0001) were significantly reduced by pravastatin compared with placebo. Change in Lp-PLA(2) activity was related to change in low-density lipoprotein cholesterol (pravastatin: r = 0.53, P <.0001, placebo: r = 0.23, P <.001) but change in Lp-PLA(2) mass was not related to change in low-density lipoprotein cholesterol. Baseline levels of Lp-PLA(2) mass and activity were not significantly associated with carotid intima-media thickness at baseline or at 4 years. CONCLUSION: Lp-PLA(2) mass and activity are significantly elevated in children with heterozygous FH compared with unaffected siblings and are significantly reduced by pravastatin therapy. (C) 2011 National Lipid Association. All rights reserve

Year: 2011
DOI identifier: 10.1016/j.jacl.2010.11.001
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Provided by: NARCIS
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