TY - JOUR
T1 - Lipoprotein-associated phospholipase A(2) mass and activity in children with heterozygous familial hypercholesterolemia and unaffected siblings: Effect of pravastatin
AU - Ryu, Sung Kee
AU - Hutten, Barbara A.
AU - Vissers, Maud N.
AU - Wiegman, Albert
AU - Kastelein, John J. P.
AU - Tsimikas, Sotirios
PY - 2011
Y1 - 2011
N2 - 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 reserved
AB - 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 reserved
U2 - https://doi.org/10.1016/j.jacl.2010.11.001
DO - https://doi.org/10.1016/j.jacl.2010.11.001
M3 - Article
C2 - 21262507
SN - 1933-2874
VL - 5
SP - 50
EP - 56
JO - Journal of clinical lipidology
JF - Journal of clinical lipidology
IS - 1
ER -