U Julius1, M Milton2, D Stoellner3, D Rader4, B Gordon5, D Polk6, E Waldmann7, K G Parhofer7, P M Moriarty8. 1. Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Germany. Electronic address: ulrich.julius@uniklinikum-dresden.de. 2. Novartis Institutes for BioMedical Research, Inc., Cambridge, MA, USA. 3. Novartis Institutes for BioMedical Research, Inc., Basel, Switzerland. 4. Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA. 5. The Rogosin Institute, New York, USA. 6. Cardiovascular Fellowship Program Brigham and Women's Hospital, Boston, USA. 7. Department of Internal Medicine II, University Hospital Munich, Germany. 8. University of Kansas Medical Center, Kansas City, USA.
Abstract
BACKGROUND: PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) increases LDL cholesterol (LDL-C) levels by stimulating the degradation of Low Density Lipoprotein receptors (LDL-r). This protein is now of high interest because antibodies which inhibit its effect on LDL-r are being developed. A severe hypercholesterolemia and / or an elevation of lipoprotein(a) can be treated with lipoprotein apheresis (LA) in high-risk patients. METHODS: We measured serum PCSK9 levels in patients eligible for the extracorporeal treatment: in 40 patients (Cohort I) who were treated with different systems before and after apheresis sessions and in the intervals between sessions. 10 patients (Cohort II) who were eligible but did not start LA yet served as controls. RESULTS: Patients' baseline serum PCSK9 levels were elevated relative to healthy volunteers and LA sessions acutely reduced the mean PCSK9 concentrations by 51%. Comparison of the effectiveness of the different LA methods demonstrated the DSA and HELP were more effective than the DALI system. After 24 h PCSK9 levels had returned to baseline compared to 8 days for the LDL-C concentrations to return to its pre-apheresis levels. In Cohort II baseline PCSK9 levels were similar to those in Cohort I. CONCLUSION: The acute reductions of PCSK9 by apheresis may be beneficial with respect to increasing the effectiveness of lipid-lowering drugs and with respect to an anti-atherosclerotic effect. In the future, antagonists to PCSK9 will probably be combined with or possibly replace LA in patients with a very high cardiovascular risk.
BACKGROUND:PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) increases LDL cholesterol (LDL-C) levels by stimulating the degradation of Low Density Lipoprotein receptors (LDL-r). This protein is now of high interest because antibodies which inhibit its effect on LDL-r are being developed. A severe hypercholesterolemia and / or an elevation of lipoprotein(a) can be treated with lipoprotein apheresis (LA) in high-risk patients. METHODS: We measured serum PCSK9 levels in patients eligible for the extracorporeal treatment: in 40 patients (Cohort I) who were treated with different systems before and after apheresis sessions and in the intervals between sessions. 10 patients (Cohort II) who were eligible but did not start LA yet served as controls. RESULTS:Patients' baseline serum PCSK9 levels were elevated relative to healthy volunteers and LA sessions acutely reduced the mean PCSK9 concentrations by 51%. Comparison of the effectiveness of the different LA methods demonstrated the DSA and HELP were more effective than the DALI system. After 24 h PCSK9 levels had returned to baseline compared to 8 days for the LDL-C concentrations to return to its pre-apheresis levels. In Cohort II baseline PCSK9 levels were similar to those in Cohort I. CONCLUSION: The acute reductions of PCSK9 by apheresis may be beneficial with respect to increasing the effectiveness of lipid-lowering drugs and with respect to an anti-atherosclerotic effect. In the future, antagonists to PCSK9 will probably be combined with or possibly replace LA in patients with a very high cardiovascular risk.
Authors: Xiao Meng Zhang; Yan Hong Gu; Hao Deng; Zheng Quan Xu; Ze Yuan Zhong; Xia Jie Lyu; Hui Min Jin; Xiu Hong Yang Journal: Front Cardiovasc Med Date: 2021-07-07