Decreased production of low density lipoprotein by atorvastatin after apheresis in homozygous familial hypercholesterolemia

Autor: A D Marais, R P Naoumova, J C Firth, C Penny, C K Neuwirth, G R Thompson
Jazyk: angličtina
Rok vydání: 1997
Předmět:
Zdroj: Journal of Lipid Research, Vol 38, Iss 10, Pp 2071-2078 (1997)
Druh dokumentu: article
ISSN: 0022-2275
DOI: 10.1016/S0022-2275(20)37137-6
Popis: Apheresis only partially controls raised low density lipoprotein cholesterol levels in patients with homozygous familial hypercholesterolemia, who usually respond poorly to lipid-lowering drugs. The efficacy and mechanism of action of a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, atorvastatin, was therefore investigated in seven homozygotes undergoing apheresis. One receptor-negative and six receptor-defective homozygotes undergoing plasma exchange or LDL apheresis every 2 weeks were studied during 2 months each on placebo and on atorvastatin 80 mg daily. Changes in plasma lipids and mevalonic acid, an index of cholesterol synthesis, were measured and the kinetics of the rebound of low density lipoprotein cholesterol and apolipoprotein B after apheresis were analyzed. All subjects had significant improvements on atorvastatin. Mean decreases in low density lipoprotein cholesterol were 31% greater both pre- and post-apheresis on atorvastatin compared with placebo, accompanied by a 63% decrease in mevalonic acid. Percentage changes in low density lipoprotein cholesterol and mevalonic acid were closely correlated (r = 0.89, P = 0.007). The mean production rates of low density lipoprotein cholesterol and apolipoprotein B were 21% and 25% lower, respectively, on atorvastatin than on placebo (P < 0.005 and
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