To determine lipoprotein particle concentrations and size in children with familial hypercholesterolemia (FH) and investigate the effect of pravastatin therapy on these measures.Study design
Lipoprotein particle concentrations and sizes were examined by nuclear magnetic resonance (NMR) spectroscopy in 144 children with FH and 45 unaffected siblings. The effect of pravastatin therapy (20 to 40 mg) on lipoprotein particle concentration and size were compared with placebo after 1 year of treatment, using analysis of covariance.Results
Compared with the unaffected siblings, the children with FH had significantly higher concentrations of very-low-density lipoprotein (VLDL) particles (115.6 nmol/L vs 51.2 nmol/L;P< .001) and low-density lipoprotein (LDL) particles (1726.8 nmol/L vs 955.3 nmol/L;P< .001), and lower concentrations of high-density lipoprotein (HDL) particles (23.2 μmol/L vs 26.9 μmol/L;P< .001). Compared with placebo, pravastatin therapy decreased the concentration of VLDL particles by 35.9 nmol/L (P< .001), of total LDL particles by 342.7 nmol/L (P< .001), of large LDL particles by 189.5 nmol/L (P< .001), and of small LDL particles by 156.2 nmol/L (P= .152), but increased the concentration of total HDL particles by 2.2 μmol/L (P< .001), of large HDL particles by 1.0 μmol/L (P= .006), and of medium HDL particles by 1.1 μmol/L (P= .003). VLDL particle size increased by 1.0 nm (P= .032).Conclusions
Compared with their healthy siblings, children with FH have an atherogenic lipoprotein profile based on their lipoprotein distribution and lipoprotein particle diameter. Pravastatin therapy can improve, but not fully restore, these lipoprotein abnormalities toward normal levels in these children.