Effect of PCSK9 inhibition with evolocumab on lipoprotein subfractions in familial dysbetalipoproteinemia (type III hyperlipidemia).
<h4>Background and aims</h4>Familial dysbetalipoproteinemia (FDBL) is a rare inborn lipid disorder characterized by the formation of abnormal triglyceride- and cholesterol-rich lipoproteins (remnant particles). Patients with FDBL have a high risk for atherosclerotic disease. The effect o...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0265838 |
| _version_ | 1811306092452380672 |
|---|---|
| author | Elisa Waldmann Liya Wu Kristina Busygina Julia Altenhofer Kerstin Henze Alexander Folwaczny Klaus G Parhofer |
| author_facet | Elisa Waldmann Liya Wu Kristina Busygina Julia Altenhofer Kerstin Henze Alexander Folwaczny Klaus G Parhofer |
| author_sort | Elisa Waldmann |
| collection | DOAJ |
| description | <h4>Background and aims</h4>Familial dysbetalipoproteinemia (FDBL) is a rare inborn lipid disorder characterized by the formation of abnormal triglyceride- and cholesterol-rich lipoproteins (remnant particles). Patients with FDBL have a high risk for atherosclerotic disease. The effect of PCSK9 inhibition on lipoproteins and its subfractions has not been evaluated in FDBL.<h4>Methods</h4>Three patients (65±7 years, 23±3 kg/m2, 2 females) with FDBL (diagnosed by isoelectrofocusing) and atherosclerosis (coronary and/or cerebro-vascular and/or peripheral arterial disease) resistant or intolerant to statin and fibrate therapy received evolocumab (140mg every 14 days). In addition to a fasting lipid profile (preparative ultracentrifugation), apoB and cholesterol concentrations were determined in 15 lipoprotein-subfractions (density gradient ultracentrifugation; d 1.006-1.21g/ml) before and after 12 weeks of evolocumab treatment. Patients with LDL-hypercholesterolemia (n = 8, 56±8 years, 31±7 kg/m2) and mixed hyperlipidemia (n = 5, 68±12 years, 30±1 kg/m2) also receiving evolocumab for 12 weeks were used for comparison.<h4>Results</h4>All patients tolerated PCSK9 inhibition well. PCSK9 inhibitors reduced cholesterol (29-37%), non-HDL-cholesterol (36-50%) and apoB (40-52%) in all patient groups including FDBL. In FDBL, PCSK9 inhibition reduced VLDL-cholesterol and the concentration of apoB containing lipoproteins throughout the whole density spectrum (VLDL, IDL, remnants, LDL). Lipoprotein(a) was decreased in all patient groups to a similar extent.<h4>Conclusions</h4>This indicates that the dominant fraction of apoB-containing lipoproteins is reduced with PCSK9 inhibition, i.e. LDL in hypercholesterolemia and mixed hyperlipidemia, and cholesterol-rich VLDL, remnants and LDL in FDBL. PCSK9 inhibition may be a treatment option in patients with FDBL resistant or intolerant to statin and/or fibrate therapy. |
| first_indexed | 2024-04-13T08:38:13Z |
| format | Article |
| id | doaj.art-bfb3beb0cd004814b3bea74e507b11df |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T08:38:13Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-bfb3beb0cd004814b3bea74e507b11df2022-12-22T02:54:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01173e026583810.1371/journal.pone.0265838Effect of PCSK9 inhibition with evolocumab on lipoprotein subfractions in familial dysbetalipoproteinemia (type III hyperlipidemia).Elisa WaldmannLiya WuKristina BusyginaJulia AltenhoferKerstin HenzeAlexander FolwacznyKlaus G Parhofer<h4>Background and aims</h4>Familial dysbetalipoproteinemia (FDBL) is a rare inborn lipid disorder characterized by the formation of abnormal triglyceride- and cholesterol-rich lipoproteins (remnant particles). Patients with FDBL have a high risk for atherosclerotic disease. The effect of PCSK9 inhibition on lipoproteins and its subfractions has not been evaluated in FDBL.<h4>Methods</h4>Three patients (65±7 years, 23±3 kg/m2, 2 females) with FDBL (diagnosed by isoelectrofocusing) and atherosclerosis (coronary and/or cerebro-vascular and/or peripheral arterial disease) resistant or intolerant to statin and fibrate therapy received evolocumab (140mg every 14 days). In addition to a fasting lipid profile (preparative ultracentrifugation), apoB and cholesterol concentrations were determined in 15 lipoprotein-subfractions (density gradient ultracentrifugation; d 1.006-1.21g/ml) before and after 12 weeks of evolocumab treatment. Patients with LDL-hypercholesterolemia (n = 8, 56±8 years, 31±7 kg/m2) and mixed hyperlipidemia (n = 5, 68±12 years, 30±1 kg/m2) also receiving evolocumab for 12 weeks were used for comparison.<h4>Results</h4>All patients tolerated PCSK9 inhibition well. PCSK9 inhibitors reduced cholesterol (29-37%), non-HDL-cholesterol (36-50%) and apoB (40-52%) in all patient groups including FDBL. In FDBL, PCSK9 inhibition reduced VLDL-cholesterol and the concentration of apoB containing lipoproteins throughout the whole density spectrum (VLDL, IDL, remnants, LDL). Lipoprotein(a) was decreased in all patient groups to a similar extent.<h4>Conclusions</h4>This indicates that the dominant fraction of apoB-containing lipoproteins is reduced with PCSK9 inhibition, i.e. LDL in hypercholesterolemia and mixed hyperlipidemia, and cholesterol-rich VLDL, remnants and LDL in FDBL. PCSK9 inhibition may be a treatment option in patients with FDBL resistant or intolerant to statin and/or fibrate therapy.https://doi.org/10.1371/journal.pone.0265838 |
| spellingShingle | Elisa Waldmann Liya Wu Kristina Busygina Julia Altenhofer Kerstin Henze Alexander Folwaczny Klaus G Parhofer Effect of PCSK9 inhibition with evolocumab on lipoprotein subfractions in familial dysbetalipoproteinemia (type III hyperlipidemia). PLoS ONE |
| title | Effect of PCSK9 inhibition with evolocumab on lipoprotein subfractions in familial dysbetalipoproteinemia (type III hyperlipidemia). |
| title_full | Effect of PCSK9 inhibition with evolocumab on lipoprotein subfractions in familial dysbetalipoproteinemia (type III hyperlipidemia). |
| title_fullStr | Effect of PCSK9 inhibition with evolocumab on lipoprotein subfractions in familial dysbetalipoproteinemia (type III hyperlipidemia). |
| title_full_unstemmed | Effect of PCSK9 inhibition with evolocumab on lipoprotein subfractions in familial dysbetalipoproteinemia (type III hyperlipidemia). |
| title_short | Effect of PCSK9 inhibition with evolocumab on lipoprotein subfractions in familial dysbetalipoproteinemia (type III hyperlipidemia). |
| title_sort | effect of pcsk9 inhibition with evolocumab on lipoprotein subfractions in familial dysbetalipoproteinemia type iii hyperlipidemia |
| url | https://doi.org/10.1371/journal.pone.0265838 |
| work_keys_str_mv | AT elisawaldmann effectofpcsk9inhibitionwithevolocumabonlipoproteinsubfractionsinfamilialdysbetalipoproteinemiatypeiiihyperlipidemia AT liyawu effectofpcsk9inhibitionwithevolocumabonlipoproteinsubfractionsinfamilialdysbetalipoproteinemiatypeiiihyperlipidemia AT kristinabusygina effectofpcsk9inhibitionwithevolocumabonlipoproteinsubfractionsinfamilialdysbetalipoproteinemiatypeiiihyperlipidemia AT juliaaltenhofer effectofpcsk9inhibitionwithevolocumabonlipoproteinsubfractionsinfamilialdysbetalipoproteinemiatypeiiihyperlipidemia AT kerstinhenze effectofpcsk9inhibitionwithevolocumabonlipoproteinsubfractionsinfamilialdysbetalipoproteinemiatypeiiihyperlipidemia AT alexanderfolwaczny effectofpcsk9inhibitionwithevolocumabonlipoproteinsubfractionsinfamilialdysbetalipoproteinemiatypeiiihyperlipidemia AT klausgparhofer effectofpcsk9inhibitionwithevolocumabonlipoproteinsubfractionsinfamilialdysbetalipoproteinemiatypeiiihyperlipidemia |