Lipoprotein Apheresis for Lipoprotein(a)-Associated Cardiovascular Disease: Prospective 5 Years of Follow-Up and Apolipoprotein(a) Characterization

Eberhard Roeseler, Ulrich Julius, Franz Heigl, Ralf Spitthoever, Dennis Heutling, Paul Breitenberger, Josef Leebmann, Walter Lehmacher, Pia R Kamstrup, Børge G Nordestgaard, Winfried Maerz, Asma Noureen, Konrad Schmidt, Florian Kronenberg, Andreas Heibges, Reinhard Klingel, Pro(a)LiFe-Study Group

88 Citations (Scopus)

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 longterm 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.

Original languageEnglish
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume36
Issue number9
Pages (from-to)2019-2027
Number of pages9
ISSN1079-5642
DOIs
Publication statusPublished - 1 Sept 2016

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