{"entity": "researcher", "timestamp": "2026-07-12T08:31:09.766Z", "family": "Wallentin", "given": "Lars", "initials": "L", "orcid": "0000-0003-0378-6531", "affiliations": ["Department of Medical Sciences, Cardiology, Uppsala University, Akademiska sjukhuset Entrance 40, 751 85 Uppsala, Sweden", "Uppsala Clinical Research Center, Uppsala University, Dag Hammarskj\u00f6lds V\u00e4g 38, 751 85 Uppsala, Sweden"], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/388a76db2e4d423882d1cf2bf6b7d985.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/388a76db2e4d423882d1cf2bf6b7d985"}}, "publications": [{"entity": "publication", "iuid": "b736476c34b9439da7adaec3604dbd0c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b736476c34b9439da7adaec3604dbd0c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b736476c34b9439da7adaec3604dbd0c"}}, "title": "Vascular endothelial growth factor-D plasma levels and VEGFD genetic variants are independently associated with outcomes in patients with cardiovascular disease.", "authors": [{"family": "Davidsson", "given": "Pia", "initials": "P", "orcid": "0000-0002-4775-5828", "researcher": {"href": "https://publications.scilifelab.se/researcher/23f2792fe59f463dba3e347ff1efb2bc.json"}}, {"family": "Eketj\u00e4ll", "given": "Susanna", "initials": "S"}, {"family": "Eriksson", "given": "Niclas", "initials": "N", "orcid": "0000-0002-2152-4343", "researcher": {"href": "https://publications.scilifelab.se/researcher/64611a83caba46d597f45371b77de26b.json"}}, {"family": "Walentinsson", "given": "Anna", "initials": "A"}, {"family": "Becker", "given": "Richard C", "initials": "RC"}, {"family": "Cavallin", "given": "Anders", "initials": "A"}, {"family": "Bogstedt", "given": "Anna", "initials": "A"}, {"family": "Coll\u00e9n", "given": "Anna", "initials": "A"}, {"family": "Held", "given": "Claes", "initials": "C", "orcid": "0000-0001-9402-7404", "researcher": {"href": "https://publications.scilifelab.se/researcher/88c69f319fce4852aab37e02a75ed525.json"}}, {"family": "James", "given": "Stefan", "initials": "S"}, {"family": "Siegbahn", "given": "Agneta", "initials": "A"}, {"family": "Stewart", "given": "Ralph", "initials": "R", "orcid": "0000-0002-6167-1225", "researcher": {"href": "https://publications.scilifelab.se/researcher/493d2ac878264e0d98736945d8fdbb4d.json"}}, {"family": "Storey", "given": "Robert F", "initials": "RF"}, {"family": "White", "given": "Harvey", "initials": "H"}, {"family": "Wallentin", "given": "Lars", "initials": "L", "orcid": "0000-0003-0378-6531", "researcher": {"href": "https://publications.scilifelab.se/researcher/388a76db2e4d423882d1cf2bf6b7d985.json"}}], "type": "journal article", "published": "2023-07-04", "journal": {"title": "Cardiovasc. Res.", "issn": "1755-3245", "volume": "119", "issue": "7", "pages": "1596-1605", "issn-l": "0008-6363"}, "abstract": "The vascular endothelial growth factor (VEGF) family is involved in pathophysiological mechanisms underlying cardiovascular (CV) diseases. The aim of this study was to investigate the associations between circulating VEGF ligands and/or soluble receptors and CV outcome in patients with acute coronary syndrome (ACS) and chronic coronary syndrome (CCS).\n\nLevels of VEGF biomarkers, including bFGF, Flt-1, KDR (VEGFR2), PlGF, Tie-2, VEGF-A, VEGF-C, and VEGF-D, were measured in the PLATO ACS cohort (n = 2091, discovery cohort). Subsequently, VEGF-D was also measured in the STABILITY CCS cohort (n = 4015, confirmation cohort) to verify associations with CV outcomes. Associations between plasma VEGF-D and outcomes were analysed by multiple Cox regression models with hazard ratios (HR [95% CI]) comparing the upper vs. the lower quartile of VEGF-D. Genome-wide association study (GWAS) of VEGF-D in PLATO identified SNPs that were used as genetic instruments in Mendelian randomization (MR) meta-analyses vs. clinical endpoints. GWAS and MR were performed in patients with ACS from PLATO (n = 10 013) and FRISC-II (n = 2952), and with CCS from the STABILITY trial (n = 10 786). VEGF-D, KDR, Flt-1, and PlGF showed significant association with CV outcomes. VEGF-D was most strongly associated with CV death (P = 3.73e-05, HR 1.892 [1.419, 2.522]). Genome-wide significant associations with VEGF-D levels were identified at the VEGFD locus on chromosome Xp22. MR analyses of the combined top ranked SNPs (GWAS P-values; rs192812042, P = 5.82e-20; rs234500, P = 1.97e-14) demonstrated a significant effect on CV mortality [P = 0.0257, HR 1.81 (1.07, 3.04) per increase of one unit in log VEGF-D].\n\nThis is the first large-scale cohort study to demonstrate that both VEGF-D plasma levels and VEGFD genetic variants are independently associated with CV outcomes in patients with ACS and CCS. Measurements of VEGF-D levels and/or VEGFD genetic variants may provide incremental prognostic information in patients with ACS and CCS.", "doi": "10.1093/cvr/cvad039", "pmid": "36869765", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "NGI SNP genotyping": "Service", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "7069262"}], "notes": [], "created": "2023-04-06T13:50:07.167Z", "modified": "2023-11-29T19:15:31.361Z"}, {"entity": "publication", "iuid": "a02c0a3eaf1e456fb1859569031908a7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a02c0a3eaf1e456fb1859569031908a7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a02c0a3eaf1e456fb1859569031908a7"}}, "title": "Using multimarker screening to identify biomarkers associated with cardiovascular death in patients with atrial fibrillation.", "authors": [{"family": "Pol", "given": "Tymon", "initials": "T", "orcid": "0000-0001-6239-199X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0bf1df0dd904b579b081a3680627005.json"}}, {"family": "Hijazi", "given": "Ziad", "initials": "Z", "orcid": "0000-0002-7420-743X", "researcher": {"href": "https://publications.scilifelab.se/researcher/03d1c858fbab4b7d9c9574adf5ad51af.json"}}, {"family": "Lindb\u00e4ck", "given": "Johan", "initials": "J"}, {"family": "Oldgren", "given": "Jonas", "initials": "J", "orcid": "0000-0002-9969-3921", "researcher": {"href": "https://publications.scilifelab.se/researcher/14e1774fd1674edeaaa64a3f86d051d7.json"}}, {"family": "Alexander", "given": "John H", "initials": "JH", "orcid": "0000-0002-1444-2462", "researcher": {"href": "https://publications.scilifelab.se/researcher/468ce17f14a04afd9cfe979103f1f849.json"}}, {"family": "Connolly", "given": "Stuart J", "initials": "SJ"}, {"family": "Eikelboom", "given": "John W", "initials": "JW"}, {"family": "Ezekowitz", "given": "Michael D", "initials": "MD", "orcid": "0000-0003-3623-2252", "researcher": {"href": "https://publications.scilifelab.se/researcher/43f3a6f18de74bb6a632b1b16d1b778c.json"}}, {"family": "Granger", "given": "Christopher B", "initials": "CB"}, {"family": "Lopes", "given": "Renato D", "initials": "RD", "orcid": "0000-0003-2999-4961", "researcher": {"href": "https://publications.scilifelab.se/researcher/a98c4a6d5300452b9a3a770cff4d97e9.json"}}, {"family": "Yusuf", "given": "Salim", "initials": "S"}, {"family": "Siegbahn", "given": "Agneta", "initials": "A"}, {"family": "Wallentin", "given": "Lars", "initials": "L", "orcid": "0000-0003-0378-6531", "researcher": {"href": "https://publications.scilifelab.se/researcher/388a76db2e4d423882d1cf2bf6b7d985.json"}}], "type": "clinical study", "published": "2022-07-20", "journal": {"title": "Cardiovasc. Res.", "issn": "1755-3245", "volume": "118", "issue": "9", "pages": "2112-2123", "issn-l": "0008-6363"}, "abstract": "Atrial fibrillation (AF) is associated with higher mortality. Biomarkers may improve the understanding of key pathophysiologic processes in AF that lead to death. Using a new multiplex analytic technique, we explored the association between 268 biomarkers and cardiovascular (CV) death in anticoagulated patients with AF.\n\nA case-cohort design with 1.8- to 1.9-year follow-up. The identification cohort included 517 cases and 4057 randomly selected patients from ARISTOTLE. The validation cohort included 277 cases and 1042 randomly selected controls from RE-LY. Plasma collected at randomization was analysed with conventional immunoassays and the OLINK proximity extension assay panels: CVDII, CVDIII, and Inflammation. Association between biomarkers and CV death was evaluated using Random Survival Forest, Boruta, and adjusted Cox-regression analyses. The biomarkers most strongly and consistently associated with CV death were as follows (hazard ratio for inter-quartile comparison [95% CI]): N-terminal pro-B-type natriuretic peptide [NT-proBNP; 1.63 (1.37-1.93)], cardiac troponin T [cTnT-hs; 1.60 (1.35-1.88)], interleukin-6 [IL-6; 1.29 (1.13-1.47)], growth differentiation factor-15 [GDF-15; 1.30 (1.10-1.53)], fibroblast growth factor 23 [FGF-23; 1.21 (1.10-1.33)], urokinase receptor [uPAR; 1.38 (1.16-1.64)], trefoil factor 3 [TFF3; 1.27 (1.10-1.46)], tumour necrosis factor receptor 1 [TNFR1; 1.21 (1.01-1.45)], TNF-related apoptosis-inducing ligand receptor 2 [TRAILR2; 1.18 (1.04-1.34)], and cathepsin L1 [CTSL1; 1.22 (1.07-1.39)].\n\nIn this comprehensive screening of 268 biomarkers in anticoagulated patients with AF, the underlying mechanisms most strongly associated with CV death were cardiorenal dysfunction (NT-proBNP, cTnT-hs, CTSL1, TFF3), oxidative stress (GDF-15), inflammation (IL-6, GDF-15), calcium balance, vascular and renal dysfunction (FGF-23), fibrinolysis (suPAR), and apoptosis (TNFR1, TRAILR2). These findings provide novel insights into pathophysiologic aspects associated with CV death in AF.\n\nNCT00412984 and NCT00262600.", "doi": "10.1093/cvr/cvab262", "pmid": "34358298", "labels": {"Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9302885"}, {"db": "pii", "key": "6343453"}, {"db": "ClinicalTrials.gov", "key": "NCT00412984"}, {"db": "ClinicalTrials.gov", "key": "NCT00262600"}], "notes": [], "created": "2021-12-10T09:12:08.560Z", "modified": "2022-12-02T08:57:56.429Z"}, {"entity": "publication", "iuid": "6cab2cbebcc34f5e8cc965eb5955fdca", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6cab2cbebcc34f5e8cc965eb5955fdca.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6cab2cbebcc34f5e8cc965eb5955fdca"}}, "title": "Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality.", "authors": [{"family": "Schunk", "given": "Stefan J", "initials": "SJ"}, {"family": "Kleber", "given": "Marcus E", "initials": "ME", "orcid": "0000-0003-0663-7275", "researcher": {"href": "https://publications.scilifelab.se/researcher/a51175112cfb4721b8c9fbfdc71c4307.json"}}, {"family": "M\u00e4rz", "given": "Winfried", "initials": "W"}, {"family": "Pang", "given": "Shichao", "initials": "S", "orcid": "0000-0002-4111-2864", "researcher": {"href": "https://publications.scilifelab.se/researcher/9839ca383ecb432dafae190a3a5b583a.json"}}, {"family": "Zewinger", "given": "Stephen", "initials": "S"}, {"family": "Triem", "given": "Sarah", "initials": "S"}, {"family": "Ege", "given": "Philipp", "initials": "P"}, {"family": "Reichert", "given": "Matthias C", "initials": "MC", "orcid": "0000-0002-8192-0575", "researcher": {"href": "https://publications.scilifelab.se/researcher/a12ee4f4194f4f9c8cfecd585aa92fe9.json"}}, {"family": "Krawczyk", "given": "Marcin", "initials": "M"}, {"family": "Weber", "given": "Susanne N", "initials": "SN"}, {"family": "Jaumann", "given": "Isabella", "initials": "I"}, {"family": "Schmit", "given": "David", "initials": "D"}, {"family": "Sarakpi", "given": "Tamim", "initials": "T"}, {"family": "Wagenpfeil", "given": "Stefan", "initials": "S", "orcid": "0000-0002-4558-4041", "researcher": {"href": "https://publications.scilifelab.se/researcher/9587116dd42d44d9b5a1cc33af1d6623.json"}}, {"family": "Kramann", "given": "Rafael", "initials": "R", "orcid": "0000-0003-4048-6351", "researcher": {"href": "https://publications.scilifelab.se/researcher/d5994a0ef0594c55a01e0886f3288b3b.json"}}, {"family": "Boerwinkle", "given": "Eric", "initials": "E"}, {"family": "Ballantyne", "given": "Christie M", "initials": "CM"}, {"family": "Grove", "given": "Megan L", "initials": "ML"}, {"family": "Tragante", "given": "Vinicius", "initials": "V", "orcid": "0000-0002-8223-8957", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb83d260bc8546edba9e3e2ed2d2c752.json"}}, {"family": "Pilbrow", "given": "Anna P", "initials": "AP", "orcid": "0000-0003-1949-9449", "researcher": {"href": "https://publications.scilifelab.se/researcher/b86a1225a68e403e806a07b42e96c991.json"}}, {"family": "Richards", "given": "A Mark", "initials": "AM", "orcid": "0000-0002-2023-8177", "researcher": {"href": "https://publications.scilifelab.se/researcher/305e1cdb095145fab591d41542b578dd.json"}}, {"family": "Cameron", "given": "Vicky A", "initials": "VA", "orcid": "0000-0003-3147-683X", "researcher": {"href": "https://publications.scilifelab.se/researcher/72d115e749a34e239c336c16e35fdd64.json"}}, {"family": "Doughty", "given": "Robert N", "initials": "RN"}, {"family": "Dub\u00e9", "given": "Marie-Pierre", "initials": "M"}, {"family": "Tardif", "given": "Jean-Claude", "initials": "J"}, {"family": "Feroz-Zada", "given": "Yassamin", "initials": "Y"}, {"family": "Sun", "given": "Maxine", "initials": "M"}, {"family": "Liu", "given": "Chang", "initials": "C", "orcid": "0000-0002-8918-7224", "researcher": {"href": "https://publications.scilifelab.se/researcher/994fa918eb6142fca1897858b7b56a06.json"}}, {"family": "Ko", "given": "Yi-An", "initials": "Y"}, {"family": "Quyyumi", "given": "Arshed A", "initials": "AA"}, {"family": "Hartiala", "given": "Jaana A", "initials": "JA", "orcid": "0000-0003-4883-9318", "researcher": {"href": "https://publications.scilifelab.se/researcher/f39400df71774cf8ae408eccbe34d981.json"}}, {"family": "Tang", "given": "W H Wilson", "initials": "WHW", "orcid": "0000-0002-8335-735X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5aab6a5657004a79aeda81c22a077268.json"}}, {"family": "Hazen", "given": "Stanley L", "initials": "SL", "orcid": "0000-0001-7124-6639", "researcher": {"href": "https://publications.scilifelab.se/researcher/abce9cd916c94667a73bc348ede57a01.json"}}, {"family": "Allayee", "given": "Hooman", "initials": "H", "orcid": "0000-0002-2384-5239", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f1c610874a248c8beaa2254d319c586.json"}}, {"family": "McDonough", "given": "Caitrin W", "initials": "CW", "orcid": "0000-0001-6393-7288", "researcher": {"href": "https://publications.scilifelab.se/researcher/61630ed695424fe9a15afa6b8d7d7362.json"}}, {"family": "Gong", "given": "Yan", "initials": "Y", "orcid": "0000-0002-8218-1620", "researcher": {"href": "https://publications.scilifelab.se/researcher/a2daf12201f64608b70dac45339da354.json"}}, {"family": "Cooper-DeHoff", "given": "Rhonda M", "initials": "RM"}, {"family": "Johnson", "given": "Julie A", "initials": "JA"}, {"family": "Scholz", "given": "Markus", "initials": "M", "orcid": "0000-0002-4059-1779", "researcher": {"href": "https://publications.scilifelab.se/researcher/53d7b0e2dcdb4361b54016cb1550c5fe.json"}}, {"family": "Teren", "given": "Andrej", "initials": "A"}, {"family": "Burkhardt", "given": "Ralph", "initials": "R", "orcid": "0000-0003-1924-1202", "researcher": {"href": "https://publications.scilifelab.se/researcher/abe3ddd140b3478485f44119d18926b7.json"}}, {"family": "Martinsson", "given": "Andreas", "initials": "A"}, {"family": "Smith", "given": "J Gustav", "initials": "JG"}, {"family": "Wallentin", "given": "Lars", "initials": "L", "orcid": "0000-0003-0378-6531", "researcher": {"href": "https://publications.scilifelab.se/researcher/388a76db2e4d423882d1cf2bf6b7d985.json"}}, {"family": "James", "given": "Stefan K", "initials": "SK"}, {"family": "Eriksson", "given": "Niclas", "initials": "N", "orcid": "0000-0002-2152-4343", "researcher": {"href": "https://publications.scilifelab.se/researcher/64611a83caba46d597f45371b77de26b.json"}}, {"family": "White", "given": "Harvey", "initials": "H", "orcid": "0000-0001-7712-6750", "researcher": {"href": "https://publications.scilifelab.se/researcher/3fe685eeba0d411f8d275e3ecbf4bb3c.json"}}, {"family": "Held", "given": "Claes", "initials": "C", "orcid": "0000-0001-9402-7404", "researcher": {"href": "https://publications.scilifelab.se/researcher/88c69f319fce4852aab37e02a75ed525.json"}}, {"family": "Waterworth", "given": "Dawn", "initials": "D", "orcid": "0000-0002-9226-1317", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e78b8890897424abea48058cd4c77d2.json"}}, {"family": "Trompet", "given": "Stella", "initials": "S"}, {"family": "Jukema", "given": "J Wouter", "initials": "JW", "orcid": "0000-0002-3246-8359", "researcher": {"href": "https://publications.scilifelab.se/researcher/0479b794031d4df7bed96340b3470c19.json"}}, {"family": "Ford", "given": "Ian", "initials": "I", "orcid": "0000-0001-5927-1823", "researcher": {"href": "https://publications.scilifelab.se/researcher/317610dc46d14a2ebea4a1fc4e9cecc7.json"}}, {"family": "Stott", "given": "David J", "initials": "DJ", "orcid": "0000-0002-3110-7746", "researcher": {"href": "https://publications.scilifelab.se/researcher/c7e647358616409f9d8983f342485014.json"}}, {"family": "Sattar", "given": "Naveed", "initials": "N", "orcid": "0000-0002-1604-2593", "researcher": {"href": "https://publications.scilifelab.se/researcher/80fbc7cdcfc444acb066449f80f87181.json"}}, {"family": "Cresci", "given": "Sharon", "initials": "S", "orcid": "0000-0002-5417-1054", "researcher": {"href": "https://publications.scilifelab.se/researcher/e134fd37d561443eb2bd8c23c3aa6df9.json"}}, {"family": "Spertus", "given": "John A", "initials": "JA", "orcid": "0000-0002-2839-2611", "researcher": {"href": "https://publications.scilifelab.se/researcher/58934381001f467fa9c8ed53787956bb.json"}}, {"family": "Campbell", "given": "Hannah", "initials": "H"}, {"family": "Tierling", "given": "Sascha", "initials": "S"}, {"family": "Walter", "given": "J\u00f6rn", "initials": "J", "orcid": "0000-0003-0563-7417", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ea3e512691b4aa39c5b7c7fdcdb585d.json"}}, {"family": "Ampofo", "given": "Emmanuel", "initials": "E"}, {"family": "Niemeyer", "given": "Barbara A", "initials": "BA", "orcid": "0000-0002-6963-0575", "researcher": {"href": "https://publications.scilifelab.se/researcher/f5261a56f977404b894cd4a5bad1bbc3.json"}}, {"family": "Lipp", "given": "Peter", "initials": "P", "orcid": "0000-0003-4728-9174", "researcher": {"href": "https://publications.scilifelab.se/researcher/b96abc30cbf54fc1917b2976308c12b3.json"}}, {"family": "Schunkert", "given": "Heribert", "initials": "H"}, {"family": "B\u00f6hm", "given": "Michael", "initials": "M"}, {"family": "Koenig", "given": "Wolfgang", "initials": "W", "orcid": "0000-0002-2064-9603", "researcher": {"href": "https://publications.scilifelab.se/researcher/b358f3d797814a07a05a63364ae37d27.json"}}, {"family": "Fliser", "given": "Danilo", "initials": "D"}, {"family": "Laufs", "given": "Ulrich", "initials": "U", "orcid": "0000-0003-2620-9323", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7b26e6a8964ce2b76be17eddf2c7ac.json"}}, {"family": "Speer", "given": "Thimoteus", "initials": "T", "orcid": "0000-0002-2491-6393", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c3bc32b3f144c6080853bae7094d681.json"}}, {"family": "eQTLGen consortium", "given": "", "initials": ""}, {"family": "BIOS consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2021-05-07", "journal": {"title": "Eur. Heart J.", "issn": "1522-9645", "issn-l": "0195-668X", "volume": "42", "issue": "18", "pages": "1742-1756"}, "abstract": "Inflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1\u03b2 can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.\r\n\r\nWe explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality.\r\n\r\nThe NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.", "doi": "10.1093/eurheartj/ehab107", "pmid": "33748830", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "6179517"}, {"db": "pmc", "key": "PMC8244638"}], "notes": [], "created": "2021-08-19T13:42:03.904Z", "modified": "2021-12-07T13:39:27.736Z"}, {"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"}, {"entity": "publication", "iuid": "2fcbe860666e49c1a3a45f5de295f491", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2fcbe860666e49c1a3a45f5de295f491.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2fcbe860666e49c1a3a45f5de295f491"}}, "title": "Angiotensin-converting enzyme 2 (ACE2) levels in relation to risk factors for COVID-19 in two large cohorts of patients with atrial fibrillation.", "authors": [{"family": "Wallentin", "given": "Lars", "initials": "L", "orcid": "0000-0003-0378-6531", "researcher": {"href": "https://publications.scilifelab.se/researcher/388a76db2e4d423882d1cf2bf6b7d985.json"}}, {"family": "Lindb\u00e4ck", "given": "Johan", "initials": "J", "orcid": "0000-0002-6473-8798", "researcher": {"href": "https://publications.scilifelab.se/researcher/3cea1044231d40b5a3bf186485d97cd4.json"}}, {"family": "Eriksson", "given": "Niclas", "initials": "N", "orcid": "0000-0002-2152-4343", "researcher": {"href": "https://publications.scilifelab.se/researcher/64611a83caba46d597f45371b77de26b.json"}}, {"family": "Hijazi", "given": "Ziad", "initials": "Z"}, {"family": "Eikelboom", "given": "John W", "initials": "JW"}, {"family": "Ezekowitz", "given": "Michael D", "initials": "MD", "orcid": "0000-0003-3623-2252", "researcher": {"href": "https://publications.scilifelab.se/researcher/43f3a6f18de74bb6a632b1b16d1b778c.json"}}, {"family": "Granger", "given": "Christopher B", "initials": "CB"}, {"family": "Lopes", "given": "Renato D", "initials": "RD"}, {"family": "Yusuf", "given": "Salim", "initials": "S"}, {"family": "Oldgren", "given": "Jonas", "initials": "J", "orcid": "0000-0002-9969-3921", "researcher": {"href": "https://publications.scilifelab.se/researcher/14e1774fd1674edeaaa64a3f86d051d7.json"}}, {"family": "Siegbahn", "given": "Agneta", "initials": "A"}], "type": "journal article", "published": "2020-11-01", "journal": {"title": "Eur. Heart J.", "issn": "1522-9645", "volume": "41", "issue": "41", "pages": "4037-4046", "issn-l": "0195-668X"}, "abstract": "The global COVID-19 pandemic is caused by the SARS-CoV-2 virus entering human cells using angiotensin-converting enzyme 2 (ACE2) as a cell surface receptor. ACE2 is shed to the circulation, and a higher plasma level of soluble ACE2 (sACE2) might reflect a higher cellular expression of ACE2. The present study explored the associations between sACE2 and clinical factors, cardiovascular biomarkers, and genetic variability.\n\nPlasma and DNA samples were obtained from two international cohorts of elderly patients with atrial fibrillation (n = 3999 and n = 1088). The sACE2 protein level was measured by the Olink Proteomics\u00ae Multiplex CVD II96 \u00d7 96 panel. Levels of the biomarkers high-sensitive cardiac troponin T (hs-cTnT), N-terminal probrain natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), C-reactive protein, interleukin-6, D-dimer, and cystatin-C were determined by immunoassays. Genome-wide association studies were performed by Illumina chips. Higher levels of sACE2 were statistically significantly associated with male sex, cardiovascular disease, diabetes, and older age. The sACE2 level was most strongly associated with the levels of GDF-15, NT-proBNP, and hs-cTnT. When adjusting for these biomarkers, only male sex remained associated with sACE2. We found no statistically significant genetic regulation of the sACE2 level.\n\nMale sex and clinical or biomarker indicators of biological ageing, cardiovascular disease, and diabetes are associated with higher sACE2 levels. The levels of GDF-15 and NT-proBNP, which are associated both with the sACE2 level and a higher risk for mortality and cardiovascular disease, might contribute to better identification of risk for severe COVID-19 infection.", "doi": "10.1093/eurheartj/ehaa697", "pmid": "32984892", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "5912214"}, {"db": "pmc", "key": "PMC7543499"}, {"db": "ClinicalTrials.gov", "key": "NCT00262600"}, {"db": "ClinicalTrials.gov", "key": "NCT00412984"}], "notes": [], "created": "2020-10-20T06:59:27.289Z", "modified": "2021-12-10T09:29:55.907Z"}]}