Effects of atorvastatin on electrophoretic characteristics of LDL particles among subjects with heterozygous familial hypercholesterolemia.

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Lariviere M, Lamarche B, Pirro M, Hogue JC, Bergeron J, Gagne C, Couture P

Effects of atorvastatin on electrophoretic characteristics of LDL particles among subjects with heterozygous familial hypercholesterolemia.

Atherosclerosis. 2003 Mar;167(1):97-104.

PubMed ID

12618273 [ View in PubMed

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Abstract

The effects of the HMG CoA reductase inhibitor atorvastatin on electrophoretic characteristics of LDL particles were evaluated in 46 patients (28 males and 18 females) with heterozygous familial hypercholesterolemia (FH) aged 20-61 carrying either a negative or a defective LDL receptor gene mutation. Following a 6 week drug-free baseline period, FH heterozygotes were treated with atorvastatin (median dose: 20 mg/day, range 10-80 mg/day)) for 6 months to maintain their plasma LDL-cholesterol concentrations between 4.0 and 5.0 mmol/l. Atorvastatin treatment significantly reduced plasma total cholesterol, LDL-cholesterol and triglyceride levels and increased plasma HDL-cholesterol. Furthermore, atorvastatin treatment significantly increased LDL peak particle diameter (LDL-PPD) by 0.5% (from 255.0+/-6.2 to 256.4+/-5.5 A, P=0.004) and reduced the absolute concentration of cholesterol among small (<255 A) and large (>260 A) LDL particles by 35% (P<0.001). Changes in LDL-PPD and plasma triglyceride levels were inversely correlated (R=-0.34; P=0.02). Stepwise multiple linear regression analyses showed that 41.6% of the variation in the LDL-PPD response to atorvastatin was attributable to the initial LDL-PPD (14.4%, P=0.003), the apo E polymorphism (12.4%, P=0.02), the nature of the LDL receptor gene mutation (9.6%, P=0.01) and change in triglyceride levels (5.2%, P=0.04). Moreover, the reduction in the cholesterol content of LDL <255 A was directly correlated with the daily dosage of atorvastatin (P=0.05). Results of the present study showed that atorvastatin alters significantly LDL heterogeneity in patients at high risk of coronary heart disease (CHD) such as FH heterozygotes. These results also suggest that genetic and metabolic factors may be important determinants of atorvastatin-induced changes of LDL particle size and distribution among FH heterozygotes.

DrugBank Data that Cites this Article

Pharmaco-metabolomics

Drug	Drug Groups	Metabolite	Change	Description
Atorvastatin	Approved	Cholesterol	decreased	Atorvastatin decreases the level of Cholesterol in the blood
Atorvastatin	Approved	LDL cholesterol	decreased	Atorvastatin decreases the level of LDL cholesterol in the blood
Atorvastatin	Approved	HDL cholesterol	increased	Atorvastatin increases the level of HDL cholesterol in the blood