{"entity": "researcher", "timestamp": "2026-07-22T16:58:35.591Z", "family": "Siegbahn", "given": "Agneta", "initials": "A", "orcid": "0000-0003-3955-5671", "affiliations": ["Uppsala Clinical Research Center (UCR), Uppsala University, Uppsala, Sweden.", "Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.", "Science for Life Laboratory, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/b04f7f66e31e4c369c078c4d5d0f2a89.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/b04f7f66e31e4c369c078c4d5d0f2a89"}}, "publications": [{"entity": "publication", "iuid": "9bc062d4029f4ab999ef4edda42b4b09", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9bc062d4029f4ab999ef4edda42b4b09.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9bc062d4029f4ab999ef4edda42b4b09"}}, "title": "Development and validation of a quantitative Proximity Extension Assay instrument with 21 proteins associated with cardiovascular risk (CVD-21).", "authors": [{"family": "Siegbahn", "given": "Agneta", "initials": "A", "orcid": "0000-0003-3955-5671", "researcher": {"href": "https://publications.scilifelab.se/researcher/b04f7f66e31e4c369c078c4d5d0f2a89.json"}}, {"family": "Eriksson", "given": "Niclas", "initials": "N"}, {"family": "Assarsson", "given": "Erika", "initials": "E"}, {"family": "Lundberg", "given": "Martin", "initials": "M"}, {"family": "Ballagi", "given": "Andrea", "initials": "A"}, {"family": "Held", "given": "Claes", "initials": "C"}, {"family": "Stewart", "given": "Ralph A H", "initials": "RAH"}, {"family": "White", "given": "Harvey D", "initials": "HD"}, {"family": "\u00c5berg", "given": "Mikael", "initials": "M"}, {"family": "Wallentin", "given": "Lars", "initials": "L"}], "type": "journal article", "published": "2023-11-14", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "18", "issue": "11", "pages": "e0293465", "issn-l": "1932-6203"}, "abstract": "Treatment of cardiovascular diseases (CVD) is a substantial burden to healthcare systems worldwide. New tools are needed to improve precision of treatment by optimizing the balance between efficacy, safety, and cost. We developed a high-throughput multi-marker decision support instrument which simultaneously quantifies proteins associated with CVD.\n\nCandidate proteins independently associated with different clinical outcomes were selected from clinical studies by the screening of 368 circulating biomarkers. We then custom-designed a quantitative PEA-panel with 21 proteins (CVD-21) by including recombinant antigens as calibrator samples for normalization and absolute quantification of the proteins. The utility of the CVD-21 tool was evaluated in plasma samples from a case-control cohort of 4224 patients with chronic coronary syndrome (CCS) using multivariable Cox regression analyses and machine learning techniques. The assays in the CVD-21 tool gave good precision and high sensitivity with lower level of determination (LOD) between 0.03-0.7 pg/ml for five of the biomarkers. The dynamic range for the assays was sufficient to accurately quantify the biomarkers in the validation study except for troponin I, which in the modeling was replaced by high-sensitive cardiac troponin T (hs-TnT). We created seven different multimarker models, including a reference model with NT-proBNP, hs-TnT, GDF-15, IL-6, and cystatin C and one model with only clinical variables, for the comparison of the discriminative value of the CVD-21 tool. All models with biomarkers including hs-TnT provided similar discrimination for all outcomes, e.g. c-index between 0.68-0.86 and outperformed models using only clinical variables. Most important prognostic biomarkers were MMP-12, U-PAR, REN, VEGF-D, FGF-23, TFF3, ADM, and SCF.\n\nThe CVD-21 tool is the very first instrument which with PEA simultaneously quantifies 21 proteins with associations to different CVD. Novel pathophysiologic and prognostic information beyond that of established biomarkers were identified by a number of proteins.", "doi": "10.1371/journal.pone.0293465", "pmid": "37963145", "labels": {"Affinity Proteomics Uppsala": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10645335"}, {"db": "pii", "key": "PONE-D-23-12966"}], "notes": [], "created": "2023-11-29T19:27:41.788Z", "modified": "2023-11-29T19:27:41.805Z"}, {"entity": "publication", "iuid": "c1a6d2301da54435a1c59494b1d09e4e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c1a6d2301da54435a1c59494b1d09e4e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c1a6d2301da54435a1c59494b1d09e4e"}}, "title": "Plasma proteins associated with cardiovascular death in patients with chronic coronary heart disease: A retrospective study.", "authors": [{"family": "Wallentin", "given": "Lars", "initials": "L", "orcid": "0000-0003-0378-6531", "researcher": {"href": "https://publications.scilifelab.se/researcher/388a76db2e4d423882d1cf2bf6b7d985.json"}}, {"family": "Eriksson", "given": "Niclas", "initials": "N", "orcid": "0000-0002-2152-4343", "researcher": {"href": "https://publications.scilifelab.se/researcher/64611a83caba46d597f45371b77de26b.json"}}, {"family": "Olszowka", "given": "Maciej", "initials": "M", "orcid": "0000-0001-6013-4519", "researcher": {"href": "https://publications.scilifelab.se/researcher/912f23a5cb3d458c84aaaaad4a2b45fd.json"}}, {"family": "Grammer", "given": "Tanja B", "initials": "TB"}, {"family": "Hagstr\u00f6m", "given": "Emil", "initials": "E", "orcid": "0000-0003-3221-0144", "researcher": {"href": "https://publications.scilifelab.se/researcher/9446657edc224584a7bdfd76c8d991cf.json"}}, {"family": "Held", "given": "Claes", "initials": "C", "orcid": "0000-0001-9402-7404", "researcher": {"href": "https://publications.scilifelab.se/researcher/88c69f319fce4852aab37e02a75ed525.json"}}, {"family": "Kleber", "given": "Marcus E", "initials": "ME", "orcid": "0000-0003-0663-7275", "researcher": {"href": "https://publications.scilifelab.se/researcher/a51175112cfb4721b8c9fbfdc71c4307.json"}}, {"family": "Koenig", "given": "Wolfgang", "initials": "W", "orcid": "0000-0002-2064-9603", "researcher": {"href": "https://publications.scilifelab.se/researcher/b358f3d797814a07a05a63364ae37d27.json"}}, {"family": "M\u00e4rz", "given": "Winfried", "initials": "W", "orcid": "0000-0001-6083-8946", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae0d0dd988e846c4b8c5869b9d1f2905.json"}}, {"family": "Stewart", "given": "Ralph A H", "initials": "RAH", "orcid": "0000-0002-6167-1225", "researcher": {"href": "https://publications.scilifelab.se/researcher/493d2ac878264e0d98736945d8fdbb4d.json"}}, {"family": "White", "given": "Harvey D", "initials": "HD"}, {"family": "\u00c5berg", "given": "Mikael", "initials": "M", "orcid": "0000-0002-7858-8233", "researcher": {"href": "https://publications.scilifelab.se/researcher/90fa86e9aeaa43ea9547e48b4f3f24e3.json"}}, {"family": "Siegbahn", "given": "Agneta", "initials": "A", "orcid": "0000-0003-3955-5671", "researcher": {"href": "https://publications.scilifelab.se/researcher/b04f7f66e31e4c369c078c4d5d0f2a89.json"}}], "type": "journal article", "published": "2021-01-00", "journal": {"title": "PLoS Med.", "issn": "1549-1676", "issn-l": "1549-1277", "volume": "18", "issue": "1", "pages": "e1003513"}, "abstract": "Circulating biomarkers are associated with the development of coronary heart disease (CHD) and its complications by reflecting pathophysiological pathways and/or organ dysfunction. We explored the associations between 157 cardiovascular (CV) and inflammatory biomarkers and CV death using proximity extension assays (PEA) in patients with chronic CHD.\n\nThe derivation cohort consisted of 605 cases with CV death and 2,788 randomly selected non-cases during 3-5 years follow-up included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial between 2008 and 2010. The replication cohort consisted of 245 cases and 1,042 non-cases during 12 years follow-up included in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study between 1997 and 2000. Biomarker levels were measured with conventional immunoassays and/or with the OLINK PEA panels CVD I and Inflammation. Associations with CV death were evaluated by Random Survival Forest (RF) and Cox regression analyses. Both cohorts had the same median age (65 years) and 20% smokers, while there were slight differences in male sex (82% and 76%), hypertension (70% and 78%), and diabetes (39% and 30%) in the respective STABILITY and LURIC cohorts. The analyses identified 18 biomarkers with confirmed independent association with CV death by Boruta analyses and statistical significance (all p < 0.0001) by Cox regression when adjusted for clinical characteristics in both cohorts. Most prognostic information was carried by N-terminal prohormone of brain natriuretic peptide (NTproBNP), hazard ratio (HR for 1 standard deviation [SD] increase of the log scale of the distribution of the biomarker in the replication cohort) 2.079 (95% confidence interval [CI] 1.799-2.402), and high-sensitivity troponin T (cTnT-hs) HR 1.715 (95% CI 1.491-1.973). The other proteins with independent associations were growth differentiation factor 15 (GDF-15) HR 1.728 (95% CI 1.527-1.955), transmembrane immunoglobulin and mucin domain protein (TIM-1) HR 1.555 (95% CI 1.362-1.775), renin HR 1.501 (95% CI 1.305-1.727), osteoprotegerin (OPG) HR 1.488 (95% CI 1.297-1.708), soluble suppression of tumorigenesis 2 protein (sST2) HR 1.478 (95% CI 1.307-1.672), cystatin-C (Cys-C) HR 1.370 (95% CI 1.243-1.510), tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) HR 1.205 (95% CI 1.131-1.285), carbohydrate antigen 125 (CA-125) HR 1.347 (95% CI 1.226-1.479), brain natriuretic peptide (BNP) HR 1.399 (95% CI 1.255-1.561), interleukin 6 (IL-6) HR 1.478 (95% CI 1.316-1.659), hepatocyte growth factor (HGF) HR 1.259 (95% CI 1.134-1.396), spondin-1 HR 1.295 (95% CI 1.156-1.450), fibroblast growth factor 23 (FGF-23) HR 1.349 (95% CI 1.237-1.472), chitinase-3 like protein 1 (CHI3L1) HR 1.284 (95% CI 1.129-1.461), tumor necrosis factor receptor 1 (TNF-R1) HR 1.486 (95% CI 1.307-1.689), and adrenomedullin (AM) HR 1.750 (95% CI 1.490-2.056). The study is limited by the differences in design, size, and length of follow-up of the 2 studies and the lack of results from coronary angiograms and follow-up of nonfatal events.\n\nProfiles of levels of multiple plasma proteins might be useful for the identification of different pathophysiological pathways associated with an increased risk of CV death in patients with chronic CHD.\n\nClinicalTrials.gov NCT00799903.", "doi": "10.1371/journal.pmed.1003513", "pmid": "33439866", "labels": {"Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7817029"}, {"db": "pii", "key": "PMEDICINE-D-20-04160"}, {"db": "ClinicalTrials.gov", "key": "NCT00799903"}], "notes": [], "created": "2021-12-10T09:23:14.354Z", "modified": "2022-12-02T09:03:46.477Z"}]}