Objective:To assess causes for insufficient cholesterol-lowering response to pravastatin and plant stanol esters in children with heterozygous familial hype rcholesterolemia(HeFH)-.Study design:Nine of 16 children wit...Objective:To assess causes for insufficient cholesterol-lowering response to pravastatin and plant stanol esters in children with heterozygous familial hype rcholesterolemia(HeFH)-.Study design:Nine of 16 children with HeFH who had n ot reached normocholesterolemia(≤194 mg/dL [≤5 mmol/L])-by 1 year after trea tment(40 mg pravastatin and plant stanol ester)were called nonresponders.The 7 remaining children were responders.Serum noncholesterol sterol ratios(102 × mmol/mol of cholesterol),surrogate estimates of cholesterol absorption(cholest anol,campesterol,sitosterol)and synthesis(desmosterol and lathosterol),were studied at study baseline(on plant stanol esters)and during combination therap y with pravastatin and plant stanol esters.Results:Pravastatin decreased the s erum levels of cholesterol and cholesterol synthesis markers,and increased the ratios of cholesterol absorption markers.Compared with the responders,the nonr esponders had higher study baseline(on plant stanol esters)serum cholesterol c oncentrations(299±39 vs 251 ±35 mg/dL [7.7 ±1.0 vs 6.5 ±0.9 mmol/L];P <.0 01)and higher respective ratios of campesterol(371 ±99 vs 277 ±67 102 ×mmol /mol of cholesterol;P =.049)and sitosterol(176 ±37 vs 126 ±24 102 ×mmol/m ol of cholesterol;P =.008).The higher the ratio of cholestanol at study basel ine,the smaller the 1-year percent reduction in cholesterol(r =.556;P =.02 5).Conclusions:Pravastatin treatment increases the markers of cholesterol abso rption and decreases those of cholesterol synthesis in HeFH during simultaneous inhibition of cholesterol absorption.Combined inhibition of cholesterol absorpt ion and synthesis may not normalize serum lipids in those patients with the high est cholesterol levels,especially if signs of enhanced cholesterol absorption a re detectable.展开更多
文摘Objective:To assess causes for insufficient cholesterol-lowering response to pravastatin and plant stanol esters in children with heterozygous familial hype rcholesterolemia(HeFH)-.Study design:Nine of 16 children with HeFH who had n ot reached normocholesterolemia(≤194 mg/dL [≤5 mmol/L])-by 1 year after trea tment(40 mg pravastatin and plant stanol ester)were called nonresponders.The 7 remaining children were responders.Serum noncholesterol sterol ratios(102 × mmol/mol of cholesterol),surrogate estimates of cholesterol absorption(cholest anol,campesterol,sitosterol)and synthesis(desmosterol and lathosterol),were studied at study baseline(on plant stanol esters)and during combination therap y with pravastatin and plant stanol esters.Results:Pravastatin decreased the s erum levels of cholesterol and cholesterol synthesis markers,and increased the ratios of cholesterol absorption markers.Compared with the responders,the nonr esponders had higher study baseline(on plant stanol esters)serum cholesterol c oncentrations(299±39 vs 251 ±35 mg/dL [7.7 ±1.0 vs 6.5 ±0.9 mmol/L];P <.0 01)and higher respective ratios of campesterol(371 ±99 vs 277 ±67 102 ×mmol /mol of cholesterol;P =.049)and sitosterol(176 ±37 vs 126 ±24 102 ×mmol/m ol of cholesterol;P =.008).The higher the ratio of cholestanol at study basel ine,the smaller the 1-year percent reduction in cholesterol(r =.556;P =.02 5).Conclusions:Pravastatin treatment increases the markers of cholesterol abso rption and decreases those of cholesterol synthesis in HeFH during simultaneous inhibition of cholesterol absorption.Combined inhibition of cholesterol absorpt ion and synthesis may not normalize serum lipids in those patients with the high est cholesterol levels,especially if signs of enhanced cholesterol absorption a re detectable.
