Sotirios Tsimikas1, Sergio Fazio2, Nicholas J Viney3, Shuting Xia3, Joseph L Witztum4, Santica M Marcovina5. 1. Sulpizio Cardiovascular Center, Vascular Medicine Program, University of California San Diego, La Jolla, CA, USA; Ionis Pharmaceuticals, Carlsbad, CA, USA. Electronic address: stsimikas@ucsd.edu. 2. Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA. 3. Ionis Pharmaceuticals, Carlsbad, CA, USA. 4. Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, CA, USA. 5. Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle, WA, USA.
Abstract
BACKGROUND: Lipoprotein(a) [Lp(a)] is reported as Lp(a) particle mass (mg/dL) or molar concentration of apolipoprotein(a) [apo(a)] (nmol/L), which is considered the gold standard. Values are often converted from one measurement to the other but the validity of this is unknown. OBJECTIVES: To quantify the relationship between Lp(a) molar concentration and Lp(a) mass in the context of various Lp(a) level thresholds and apo(a) isoform size. METHODS: In all samples, Lp(a) levels in molar concentration and apo(a) isoform size were determined at the Northwest Lipid Metabolism and Diabetes Research Laboratories (NLMDRL). Lp(a) mass levels were determined at the University of California, San Diego (UCSD) (1635 samples), by 5 commercially available assays: Denka 1 and Denka 2 (each 80 samples), 2 turbidimetric assays (2545 and 2673 samples, respectively), and an enzyme-linked immunosorbent assay (2605 samples). The ratios between Lp(a) molar concentration and mass (eg, nmol/L/mg/dL) were calculated and related to apo(a) isoform size. RESULTS: The mean (SD) ratios for NLMDRL/UCSD, NLMDRL/Denka1, and NLMDRL/Denka2 were 2.42 (1.25), 1.64 (0.18), and 2.02 (0.22), respectively. The ratios for NLMDRL/UCSD, NLMDRL/Denka1, and NLMDRL/Denka2 increased by Lp(a) cutoffs, with ratios of 1.82, 1.52, and 1.87, respectively, for Lp(a) < 75 nmol/L and 2.80, 1.89, and 2.24, respectively, for Lp(a) > 125 nmol/L. For the commercial turbidimetric assays and enzyme-linked immunosorbent assay, the ratios ranged from <1 to >5. CONCLUSIONS: Lp(a) molar/mass ratios are threshold, method, and isoform dependent. A single conversion factor between assays is not appropriate. These data support the transition of Lp(a) mass assays to molar concentration to improve diagnostic and clinical interpretation of Lp(a)-mediated risk.
BACKGROUND: Lipoprotein(a) [Lp(a)] is reported as Lp(a) particle mass (mg/dL) or molar concentration of apolipoprotein(a) [apo(a)] (nmol/L), which is considered the gold standard. Values are often converted from one measurement to the other but the validity of this is unknown. OBJECTIVES: To quantify the relationship between Lp(a) molar concentration and Lp(a) mass in the context of various Lp(a) level thresholds and apo(a) isoform size. METHODS: In all samples, Lp(a) levels in molar concentration and apo(a) isoform size were determined at the Northwest Lipid Metabolism and Diabetes Research Laboratories (NLMDRL). Lp(a) mass levels were determined at the University of California, San Diego (UCSD) (1635 samples), by 5 commercially available assays: Denka 1 and Denka 2 (each 80 samples), 2 turbidimetric assays (2545 and 2673 samples, respectively), and an enzyme-linked immunosorbent assay (2605 samples). The ratios between Lp(a) molar concentration and mass (eg, nmol/L/mg/dL) were calculated and related to apo(a) isoform size. RESULTS: The mean (SD) ratios for NLMDRL/UCSD, NLMDRL/Denka1, and NLMDRL/Denka2 were 2.42 (1.25), 1.64 (0.18), and 2.02 (0.22), respectively. The ratios for NLMDRL/UCSD, NLMDRL/Denka1, and NLMDRL/Denka2 increased by Lp(a) cutoffs, with ratios of 1.82, 1.52, and 1.87, respectively, for Lp(a) < 75 nmol/L and 2.80, 1.89, and 2.24, respectively, for Lp(a) > 125 nmol/L. For the commercial turbidimetric assays and enzyme-linked immunosorbent assay, the ratios ranged from <1 to >5. CONCLUSIONS:Lp(a) molar/mass ratios are threshold, method, and isoform dependent. A single conversion factor between assays is not appropriate. These data support the transition of Lp(a) mass assays to molar concentration to improve diagnostic and clinical interpretation of Lp(a)-mediated risk.
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