Eberhard Roeseler1, Ulrich Julius1, Franz Heigl1, Ralf Spitthoever1, Dennis Heutling1, Paul Breitenberger1, Josef Leebmann1, Walter Lehmacher1, Pia R Kamstrup1, Børge G Nordestgaard1, Winfried Maerz1, Asma Noureen1, Konrad Schmidt1, Florian Kronenberg1, Andreas Heibges1, Reinhard Klingel2. 1. From the Center for Nephrology, Hypertension, and Metabolic Diseases, Hannover, Germany (E.R.); 3rd Medical Clinic, University Hospital at the Technische Universität, Dresden, Germany (U.J.); Medical Health and Care Center Kempten-Allgäu, Kempten, Germany (F.H.); Dialysis and Lipid Center North Rhine, Essen, Germany (R.S.); Clinic for Nephrology and Dialysis, Tangermuende, Germany (D.H.); KfH-Kidney Center, Germering, Germany (P.B.); 1st Medical Clinic, General Hospital, Passau, Germany (J.L.); Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany (W.L.); Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark (P.R.K., B.G.N.); Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany (W.M.); Synlab Academy, Mannheim, and Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria (W.M.); Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria (A.N., K.S., F.K.); and Apheresis Research Institute, Cologne, Germany (A.H., R.K.). 2. From the Center for Nephrology, Hypertension, and Metabolic Diseases, Hannover, Germany (E.R.); 3rd Medical Clinic, University Hospital at the Technische Universität, Dresden, Germany (U.J.); Medical Health and Care Center Kempten-Allgäu, Kempten, Germany (F.H.); Dialysis and Lipid Center North Rhine, Essen, Germany (R.S.); Clinic for Nephrology and Dialysis, Tangermuende, Germany (D.H.); KfH-Kidney Center, Germering, Germany (P.B.); 1st Medical Clinic, General Hospital, Passau, Germany (J.L.); Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany (W.L.); Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark (P.R.K., B.G.N.); Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany (W.M.); Synlab Academy, Mannheim, and Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria (W.M.); Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria (A.N., K.S., F.K.); and Apheresis Research Institute, Cologne, Germany (A.H., R.K.). klingel@apheresis-research.org.
Abstract
OBJECTIVE: Lipoprotein(a)-hyperlipoproteinemia (Lp(a)-HLP) along with progressive cardiovascular disease has been approved as indication for regular lipoprotein apheresis (LA) in Germany since 2008. We aimed to study the long-term preventive effect of LA and to assess hypothetical clinical correlations of apolipoprotein(a) (apo(a)) by analyzing genotypes and phenotypes. APPROACH AND RESULTS: This prospective observational multicenter study included 170 patients with Lp(a)-HLP and progressive cardiovascular disease (48.9 years median age at diagnosis) despite other cardiovascular risk factors, including low-density lipoprotein cholesterol had maximally been treated (mean baseline low-density lipoprotein cholesterol: measured, 2.56 mmol/L [98.9 mg/dL] and corrected, 1.72 mmol/L [66.3 mg/dL]). Patients were prospectively investigated during a 5-year period about annual incidence rates of cardiovascular events. In addition, apo(a) isoforms and polymorphisms at the apo(a) gene (LPA) were characterized. One hundred fifty-four patients (90.6%) completed 5 years of follow-up. Mean Lp(a) concentration before commencing regular LA was 108.1 mg/dL. This was reduced by a single LA treatment by 68.1% on average. Significant decline of the mean annual cardiovascular event rate was observed from 0.58±0.53 2 years before regular LA to 0.11±0.15 thereafter (P<0.0001); 95.3% of patients expressed at least 1 small apo(a) isoform. Small apo(a) isoform (35.2%) carrying phenotypes were not tagged by single-nucleotide polymorphisms rs10455872 or rs3798220. CONCLUSIONS: Results of 5 years of prospective follow-up confirm that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP. Patients clinically selected by progressive cardiovascular disease were characterized by a highly frequent expression of small apo(a) isoforms. Only Lp(a) concentration seemed to comprehensively reflect Lp(a)-associated cardiovascular risk, however.
OBJECTIVE: Lipoprotein(a)-hyperlipoproteinemia (Lp(a)-HLP) along with progressive cardiovascular disease has been approved as indication for regular lipoprotein apheresis (LA) in Germany since 2008. We aimed to study the long-term preventive effect of LA and to assess hypothetical clinical correlations of apolipoprotein(a) (apo(a)) by analyzing genotypes and phenotypes. APPROACH AND RESULTS: This prospective observational multicenter study included 170 patients with Lp(a)-HLP and progressive cardiovascular disease (48.9 years median age at diagnosis) despite other cardiovascular risk factors, including low-density lipoprotein cholesterol had maximally been treated (mean baseline low-density lipoprotein cholesterol: measured, 2.56 mmol/L [98.9 mg/dL] and corrected, 1.72 mmol/L [66.3 mg/dL]). Patients were prospectively investigated during a 5-year period about annual incidence rates of cardiovascular events. In addition, apo(a) isoforms and polymorphisms at the apo(a) gene (LPA) were characterized. One hundred fifty-four patients (90.6%) completed 5 years of follow-up. Mean Lp(a) concentration before commencing regular LA was 108.1 mg/dL. This was reduced by a single LA treatment by 68.1% on average. Significant decline of the mean annual cardiovascular event rate was observed from 0.58±0.53 2 years before regular LA to 0.11±0.15 thereafter (P<0.0001); 95.3% of patients expressed at least 1 small apo(a) isoform. Small apo(a) isoform (35.2%) carrying phenotypes were not tagged by single-nucleotide polymorphisms rs10455872 or rs3798220. CONCLUSIONS: Results of 5 years of prospective follow-up confirm that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP. Patients clinically selected by progressive cardiovascular disease were characterized by a highly frequent expression of small apo(a) isoforms. Only Lp(a) concentration seemed to comprehensively reflect Lp(a)-associated cardiovascular risk, however.
Authors: Jenny Sandmark; Anna Tigerström; Tomas Akerud; Magnus Althage; Thomas Antonsson; Stefan Blaho; Cristian Bodin; Jonas Boström; Yantao Chen; Anders Dahlén; Per-Olof Eriksson; Emma Evertsson; Tomas Fex; Ola Fjellström; David Gustafsson; Margareta Herslöf; Ryan Hicks; Emelie Jarkvist; Carina Johansson; Inge Kalies; Birgitta Karlsson Svalstedt; Fredrik Kartberg; Anne Legnehed; Sofia Martinsson; Andreas Moberg; Marianne Ridderström; Birgitta Rosengren; Alan Sabirsh; Anders Thelin; Johanna Vinblad; Annika U Wellner; Bingze Xu; Ann-Margret Östlund-Lindqvist; Wolfgang Knecht Journal: J Biol Chem Date: 2020-03-04 Impact factor: 5.157