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  • Title: Serum noncholesterol sterols in children with heterozygous familial hypercholesterolemia undergoing pravastatin therapy.
    Author: Hedman M, Miettinen TA, Gylling H, Ketomäki A, Antikainen M.
    Journal: J Pediatr; 2006 Feb; 148(2):241-6. PubMed ID: 16492436.
    Abstract:
    OBJECTIVE: To assess causes for insufficient cholesterol-lowering response to pravastatin and plant stanol esters in children with heterozygous familial hypercholesterolemia (HeFH). STUDY DESIGN: Nine of 16 children with HeFH who had not reached normocholesterolemia (< or =194 mg/dL [< or =5 mmol/L]) by 1 year after treatment (40 mg pravastatin and plant stanol ester) were called nonresponders. The 7 remaining children were responders. Serum noncholesterol sterol ratios (10(2) x mmol/mol of cholesterol), surrogate estimates of cholesterol absorption (cholestanol, campesterol, sitosterol) and synthesis (desmosterol and lathosterol), were studied at study baseline (on plant stanol esters) and during combination therapy with pravastatin and plant stanol esters. RESULTS: Pravastatin decreased the serum levels of cholesterol and cholesterol synthesis markers, and increased the ratios of cholesterol absorption markers. Compared with the responders, the nonresponders had higher study baseline (on plant stanol esters) serum cholesterol concentrations (299 +/- 39 vs 251 +/- 35 mg/dL [7.7 +/- 1.0 vs 6.5 +/- 0.9 mmol/L]; P <.001) and higher respective ratios of campesterol (371 +/- 99 vs 277 +/- 67 10(2) x mmol/mol of cholesterol; P = .049) and sitosterol (176 +/- 37 vs 126 +/- 24 10(2) x mmol/mol of cholesterol; P = .008). The higher the ratio of cholestanol at study baseline, the smaller the 1-year percent reduction in cholesterol (r = .556; P = .025). CONCLUSIONS: Pravastatin treatment increases the markers of cholesterol absorption and decreases those of cholesterol synthesis in HeFH during simultaneous inhibition of cholesterol absorption. Combined inhibition of cholesterol absorption and synthesis may not normalize serum lipids in those patients with the highest cholesterol levels, especially if signs of enhanced cholesterol absorption are detectable.
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