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Journal of Clinical Lipidology
Year: 2011  |  Volume: 5  |  Issue: 1  |  Page No.: 50 - 56

Lipoprotein-associated phospholipase A2 mass and activity in children with heterozygous familial hypercholesterolemia and unaffected siblings: Effect of pravastatin

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

Abstract:

Background

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an independent risk factor of cardiovascular disease and a target of treatment. Lp-PLA2 levels in children have not been previously reported. The effect of statin therapy on Lp-PLA2 mass and activity in children with familial hypercholesterolemia (FH) is also not known.

Methods

Lp-PLA2 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-PLA2 mass and activity levels were correlated with changes in carotid intima-media thickness during 4 years of follow-up.

Results

Baseline levels of Lp-PLA2 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-PLA2 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-PLA2 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-PLA2 mass was not related to change in low-density lipoprotein cholesterol. Baseline levels of Lp-PLA2 mass and activity were not significantly associated with carotid intima-media thickness at baseline or at 4 years.

Conclusion

Lp-PLA2 mass and activity are significantly elevated in children with heterozygous FH compared with unaffected siblings and are significantly reduced by pravastatin therapy.

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