1. Lomitapide affects HDL composition and function
- Author
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J.E. Roeters van Lennep, Monique T. Mulder, Maria Pia Adorni, Laura Calabresi, Angelo B. Cefalù, Franco Bernini, R. Yahya, Eric J.G. Sijbrands, Elda Favari, Monica Gomaraschi, Maurizio Averna, Adrie J.M. Verhoeven, Francesca Zimetti, Yahya, R., Favari, E., Calabresi, L., Verhoeven, A., Zimetti, F., Adorni, M., Gomaraschi, M., Averna, M., Cefalù, A., Bernini, F., Sijbrands, E., Mulder, M., Roeters van Lennep, J., and Internal Medicine
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Settore MED/09 - Medicina Interna ,HDL ,Homozygous familial hypercholesterolemia ,Familial hypercholesterolemia ,030204 cardiovascular system & hematology ,Hyperlipoproteinemia Type II ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,In patient ,Clinical efficacy ,Cholesterol ,business.industry ,Cholesterol, HDL ,Homozygote ,nutritional and metabolic diseases ,Cholesterol, LDL ,Cholesterol efflux capacity ,Atherosclerosis ,medicine.disease ,Cholesterol lowering drugs ,Lomitapide ,Phenotype ,Treatment Outcome ,030104 developmental biology ,Endocrinology ,chemistry ,Benzimidazoles ,Female ,lipids (amino acids, peptides, and proteins) ,Composition (visual arts) ,Cholesterol lowering drug ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Lipoproteins, HDL ,Cardiology and Cardiovascular Medicine ,business ,ATP Binding Cassette Transporter 1 - Abstract
Background Lomitapide reduces low-density lipoprotein-cholesterol (LDL-C) but also high-density lipoprotein-cholesterol (HDL-C) levels. The latter may reduce the clinical efficacy of lomitapide. We investigated the effect of lomitapide on HDL-C levels and on cholesterol efflux capacity (CEC) of HDL in patients with homozygous familial hypercholesterolemia (HoFH). Methods and results Four HoFH patients were treated with increasing dosages of lomitapide. Lomitapide decreased LDL-C (range −34 to −89%). Total HDL-C levels decreased (range −16 to −34%) with a shift to buoyant HDL. ABCA1-mediated CEC decreased in all patients (range −39 to −99%). The changes of total, ABCG1- and SR-BI-mediated CEC were less consistent. Conclusion Lomitapide decreased LDL-C and HDL-C levels. Our report raises the hypothesis that the anti-atherogenic potential of HDL seems to be unaffected as total CEC did not seem to change consistently. Combined with the reduction of atherogenic lipoproteins, the net effect of lomitapide appears to be beneficial in HoFH patients.
- Published
- 2016