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

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dc.contributor.authorMarais, A David
dc.contributor.authorNaoumova, R P
dc.contributor.authorFirth, J C
dc.contributor.authorPenny, C
dc.contributor.authorNeuwirth, C K Y
dc.contributor.authorThompson, G R
dc.date.accessioned2021-10-08T07:22:53Z
dc.date.available2021-10-08T07:22:53Z
dc.date.issued1997
dc.description.abstractApheresis 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 <0.02) but changes in mean fractional clearance rates were not statistically significant. We conclude that atorvastatin enhances the efficacy of plasma exchange and low density lipoprotein apheresis in patients who lack low density lipoprotein receptors. This effect appears to be due to marked inhibition of cholesterol synthesis which results in a decreased rate of production of low density lipoprotein.
dc.identifier.apacitationMarais, A. D., Naoumova, R. P., Firth, J. C., Penny, C., Neuwirth, C. K. Y., & Thompson, G. R. (1997). Decreased production of low density lipoprotein by atorvastatin after apheresis in homozygous familial hypercholesterolemia. <i>The Journal of Lipid Research</i>, 38(10), 2071 - 208. http://hdl.handle.net/11427/35017en_ZA
dc.identifier.chicagocitationMarais, A David, R P Naoumova, J C Firth, C Penny, C K Y Neuwirth, and G R Thompson "Decreased production of low density lipoprotein by atorvastatin after apheresis in homozygous familial hypercholesterolemia." <i>The Journal of Lipid Research</i> 38, 10. (1997): 2071 - 208. http://hdl.handle.net/11427/35017en_ZA
dc.identifier.citationMarais, A.D., Naoumova, R.P., Firth, J.C., Penny, C., Neuwirth, C.K.Y. & Thompson, G.R. 1997. Decreased production of low density lipoprotein by atorvastatin after apheresis in homozygous familial hypercholesterolemia. <i>The Journal of Lipid Research.</i> 38(10):2071 - 208. http://hdl.handle.net/11427/35017en_ZA
dc.identifier.issn0022-2275
dc.identifier.issn1539-7262
dc.identifier.ris TY - Journal Article AU - Marais, A David AU - Naoumova, R P AU - Firth, J C AU - Penny, C AU - Neuwirth, C K Y AU - Thompson, G R AB - 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 <0.02) but changes in mean fractional clearance rates were not statistically significant. We conclude that atorvastatin enhances the efficacy of plasma exchange and low density lipoprotein apheresis in patients who lack low density lipoprotein receptors. This effect appears to be due to marked inhibition of cholesterol synthesis which results in a decreased rate of production of low density lipoprotein. DA - 1997 DB - OpenUCT DP - University of Cape Town IS - 10 J1 - The Journal of Lipid Research LK - https://open.uct.ac.za PY - 1997 SM - 0022-2275 SM - 1539-7262 T1 - Decreased production of low density lipoprotein by atorvastatin after apheresis in homozygous familial hypercholesterolemia TI - Decreased production of low density lipoprotein by atorvastatin after apheresis in homozygous familial hypercholesterolemia UR - http://hdl.handle.net/11427/35017 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/35017
dc.identifier.vancouvercitationMarais AD, Naoumova RP, Firth JC, Penny C, Neuwirth CKY, Thompson GR. Decreased production of low density lipoprotein by atorvastatin after apheresis in homozygous familial hypercholesterolemia. The Journal of Lipid Research. 1997;38(10):2071 - 208. http://hdl.handle.net/11427/35017.en_ZA
dc.language.isoeng
dc.publisher.departmentDepartment of Medicine
dc.publisher.facultyFaculty of Health Sciences
dc.sourceThe Journal of Lipid Research
dc.source.journalissue10
dc.source.journalvolume38
dc.source.pagination2071 - 208
dc.source.urihttps://dx.doi.org/10.7196/sajs.718
dc.subject.otherAdolescent
dc.subject.otherAdult
dc.subject.otherAnticholesteremic Agents
dc.subject.otherApolipoproteins B
dc.subject.otherAtorvastatin Calcium
dc.subject.otherBlood Component Removal
dc.subject.otherCholesterol, LDL
dc.subject.otherCombined Modality Therapy
dc.subject.otherEnzyme Inhibitors
dc.subject.otherFemale
dc.subject.otherHeptanoic Acids
dc.subject.otherHomozygote
dc.subject.otherHumans
dc.subject.otherHyperlipoproteinemia Type II
dc.subject.otherKinetics
dc.subject.otherLipids
dc.titleDecreased production of low density lipoprotein by atorvastatin after apheresis in homozygous familial hypercholesterolemia
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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