Hubert Scharnagl1, Tatjana Stojakovic2, Benjamin Dieplinger3, Hans Dieplinger4, Gertraud Erhart4, Gerhard M Kostner5, Markus Herrmann2, Winfried März6, Tanja B Grammer7. 1. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. Electronic address: hubert.scharnagl@medunigraz.at. 2. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. 3. Department of Laboratory Medicine, Konventhospital Barmherzige Brueder, Linz, Austria. 4. Institute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, Austria. 5. Institute of Molecular Biology and Biochemistry, Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging Medical University of Graz, Austria. 6. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria; Medical Faculty Mannheim, University of Heidelberg, Germany; SYNLAB Academy, SYNLAB Holding Deutschland GmbH, Mannheim and Augsburg, Germany. 7. Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty Mannheim, University of Heidelberg, Germany.
Abstract
BACKGROUND AND AIMS: Lipoprotein (a) [Lp(a)] is an established causal risk factor for cardiovascular disease (CVD), independently of low-density lipoproteins (LDL) and other risk factors. The recognition of Lp(a) as an atherogenic molecule has raised the demand for reliable quantification methods in the clinical laboratory. The aim of this work is to compare commercial immunochemical assays. METHODS: We measured Lp(a) serum concentrations using six different assays, providing Lp(a) in mg/dl (Denka Seiken, Abbott Quantia, Beckman, Diasys 21FS, and Siemens N Latex) or in nmol/l (Roche TinaQuant, Diasys 21 FS) in 144 serum samples covering the clinically relevant range of Lp(a) concentrations. All assays relied on five-point calibrations using calibrators provided by the manufacturers. Apolipoprotein(a) phenotyping was performed by sodium dodecyl sulfate-agarose gel electrophoresis (SDS-agarose) followed by immunoblotting. RESULTS: Most bivariate correlation coefficients were greater than 0.90. Compared to an established IFCC-proposed reference material, the results of the different assays diverged from the target values (43.3 mg/dl or 96.6 nmol/l) by -8% (Siemens N Latex) and +22% (Abbott Quantia). Stratification of the samples into five groups with increasing Lp(a) concentrations and difference plots showed that the differences among assays were concentration-dependent. Some assays overestimated Lp(a) at high concentrations compared to the Denka Seiken assay. CONCLUSIONS: Current commercial immunological assays for measuring Lp(a) concentrations are differently calibrated. Their biases differ significantly across the clinically relevant concentration range in a non-linear manner. This is not conclusively explained by apolipoprotein (a) phenotypes. Further international efforts to harmonize assays for Lp(a) are needed.
BACKGROUND AND AIMS: Lipoprotein (a) [Lp(a)] is an established causal risk factor for cardiovascular disease (CVD), independently of low-density lipoproteins (LDL) and other risk factors. The recognition of Lp(a) as an atherogenic molecule has raised the demand for reliable quantification methods in the clinical laboratory. The aim of this work is to compare commercial immunochemical assays. METHODS: We measured Lp(a) serum concentrations using six different assays, providing Lp(a) in mg/dl (Denka Seiken, Abbott Quantia, Beckman, Diasys 21FS, and Siemens N Latex) or in nmol/l (Roche TinaQuant, Diasys 21 FS) in 144 serum samples covering the clinically relevant range of Lp(a) concentrations. All assays relied on five-point calibrations using calibrators provided by the manufacturers. Apolipoprotein(a) phenotyping was performed by sodium dodecyl sulfate-agarose gel electrophoresis (SDS-agarose) followed by immunoblotting. RESULTS: Most bivariate correlation coefficients were greater than 0.90. Compared to an established IFCC-proposed reference material, the results of the different assays diverged from the target values (43.3 mg/dl or 96.6 nmol/l) by -8% (Siemens N Latex) and +22% (Abbott Quantia). Stratification of the samples into five groups with increasing Lp(a) concentrations and difference plots showed that the differences among assays were concentration-dependent. Some assays overestimated Lp(a) at high concentrations compared to the Denka Seiken assay. CONCLUSIONS: Current commercial immunological assays for measuring Lp(a) concentrations are differently calibrated. Their biases differ significantly across the clinically relevant concentration range in a non-linear manner. This is not conclusively explained by apolipoprotein (a) phenotypes. Further international efforts to harmonize assays for Lp(a) are needed.
Authors: Lisandro D Colantonio; Vera Bittner; Monika M Safford; Santica Marcovina; Todd M Brown; Elizabeth A Jackson; Mei Li; J Antonio G López; Keri L Monda; Timothy B Plante; Shia T Kent; Paul Muntner; Robert S Rosenson Journal: J Am Heart Assoc Date: 2022-05-27 Impact factor: 6.106
Authors: Steven E Nissen; Kathy Wolski; Leslie Cho; Stephen J Nicholls; John Kastelein; Eran Leitersdorf; Ulf Landmesser; Michael Blaha; A Michael Lincoff; Ryuichi Morishita; Sotirios Tsimikas; Junhao Liu; Brian Manning; Plamen Kozlovski; Anastasia Lesogor; Tom Thuren; Taro Shibasaki; Florin Matei; Fábio Serra Silveira; Andreas Meunch; Aysha Bada; Vinod Vijan; Niels Eske Bruun; Borge G Nordestgaard Journal: Open Heart Date: 2022-10
Authors: Weili Zheng; Michael Chilazi; Jihwan Park; Vasanth Sathiyakumar; Leslie J Donato; Jeffrey W Meeusen; Mariana Lazo; Eliseo Guallar; Krishnaji R Kulkarni; Allan S Jaffe; Raul D Santos; Peter P Toth; Steven R Jones; Seth S Martin Journal: J Am Heart Assoc Date: 2022-01-13 Impact factor: 6.106
Authors: Christian Roth; Konstantin A Krychtiuk; Clemens Gangl; Lore Schrutka; Klaus Distelmaier; Johann Wojta; Christian Hengstenberg; Rudolf Berger; Walter S Speidl Journal: PLoS One Date: 2020-01-09 Impact factor: 3.240
Authors: Gregory G Schwartz; Michael Szarek; Vera A Bittner; Deepak L Bhatt; Rafael Diaz; Shaun G Goodman; J Wouter Jukema; Megan Loy; Garen Manvelian; Robert Pordy; Harvey D White; Philippe Gabriel Steg Journal: Diabetes Care Date: 2021-03-15 Impact factor: 19.112