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

详细信息    查看全文

• 作者：Sung Kee Ryu MD ; PhD^a ; Barbara A. Hutten PhD^b ; Maud N. Vissers PhD^c ; Albert Wiegman MD ; PhD^d ; John J.P. Kastelein MD ; PhD^c ; Sotirios Tsimikas MD^e ; ^{stsimikas@ucsd.edu}
• 关键词：Familial hypercholesterolemia ; Lipoproteins ; Phospholipases ; Statins
• 刊名：Journal of Clinical Lipidology
• 出版年：2011
• 出版时间：January-February 2011
• 年：2011
• 卷：5
• 期：1
• 页码：50-56
• 全文大小：194 K

文摘

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.