Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism
This research was originally published in Blood Online. Skjeflo EW, Brækkan, Ludviksen JK, Snir, Hindberg, Mollnes, Hansen. Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism. Blood. 2021;138(21):2129-2137. Prepublished November 25, 2021; D...
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Online Access: | https://hdl.handle.net/10037/24058 https://doi.org/10.1182/blood.2021010822 |
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ftunivtroemsoe:oai:munin.uit.no:10037/24058 2023-05-15T18:34:53+02:00 Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism Skjeflo, Espen Waage Brækkan, Sigrid Kufaas Ludviksen, Judith K Snir, Omri Hindberg, Kristian Mollnes, Tom Eirik Hansen, John-Bjarne 2021-11-25 https://hdl.handle.net/10037/24058 https://doi.org/10.1182/blood.2021010822 eng eng American Society of Hematology Blood Skjeflo EW, Brækkan, Ludviksen JK, Snir, Hindberg, Mollnes, Hansen. Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism. Blood. 2021;138(21):2129-2137 FRIDAID 1963584 doi:10.1182/blood.2021010822 0006-4971 1528-0020 https://hdl.handle.net/10037/24058 embargoedAccess Copyright 2021 The Author(s) Journal article Tidsskriftartikkel Peer reviewed acceptedVersion 2021 ftunivtroemsoe https://doi.org/10.1182/blood.2021010822 2022-02-16T23:57:06Z This research was originally published in Blood Online. Skjeflo EW, Brækkan, Ludviksen JK, Snir, Hindberg, Mollnes, Hansen. Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism. Blood. 2021;138(21):2129-2137. Prepublished November 25, 2021; DOI: https://doi.org/10.1182/blood.2021010822. The role of complement in the pathogenesis of venous thromboembolism (VTE) is unclear. We wanted to investigate (1) whether plasma complement component C5 (C5) levels are influenced by genetic variants or chronic inflammation and (2) the association between plasma C5 and risk of future VTE in a nested case-control study of 415 patients with VTE and 848 age- and sex-matched controls derived from the Tromsø Study. Plasma C5 levels were measured at inclusion. Odds ratios (ORs) with 95% confidence intervals (95% CIs) for provoked and unprovoked VTE across tertiles of C5 concentrations were estimated by logistic regression. Adjustment for C-reactive protein (CRP) served as a proxy for general inflammation. Whole-exome sequencing and protein quantitative trait loci analyses were performed to assess genetic influence on C5 concentrations. There was no association between genome-wide or C5-related gene variants and C5 levels. The association between plasma C5 levels and VTE risk displayed a threshold effect, where subjects with C5 levels above the lowest tertile had increased risk of VTE. Subjects in tertile 3 (highest C5 levels) had an age- and sex-adjusted OR of 1.45 (95% CI, 1.07-1.96) compared with tertile 1 (lowest). These statistics were more pronounced for unprovoked VTE (OR, 1.70; 95% CI, 1.11-2.60). Adjustments for body mass index and CRP had minor impact on risk estimates. The OR increased substantially with shorter time between blood sampling and VTE event. In conclusion, plasma C5 was associated with risk of future VTE. C5 levels were not genetically regulated and were only slightly influenced by chronic inflammation. Article in Journal/Newspaper Tromsø University of Tromsø: Munin Open Research Archive Mollnes ENVELOPE(19.361,19.361,70.084,70.084) Tromsø Blood 138 21 2129 2137 |
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University of Tromsø: Munin Open Research Archive |
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language |
English |
description |
This research was originally published in Blood Online. Skjeflo EW, Brækkan, Ludviksen JK, Snir, Hindberg, Mollnes, Hansen. Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism. Blood. 2021;138(21):2129-2137. Prepublished November 25, 2021; DOI: https://doi.org/10.1182/blood.2021010822. The role of complement in the pathogenesis of venous thromboembolism (VTE) is unclear. We wanted to investigate (1) whether plasma complement component C5 (C5) levels are influenced by genetic variants or chronic inflammation and (2) the association between plasma C5 and risk of future VTE in a nested case-control study of 415 patients with VTE and 848 age- and sex-matched controls derived from the Tromsø Study. Plasma C5 levels were measured at inclusion. Odds ratios (ORs) with 95% confidence intervals (95% CIs) for provoked and unprovoked VTE across tertiles of C5 concentrations were estimated by logistic regression. Adjustment for C-reactive protein (CRP) served as a proxy for general inflammation. Whole-exome sequencing and protein quantitative trait loci analyses were performed to assess genetic influence on C5 concentrations. There was no association between genome-wide or C5-related gene variants and C5 levels. The association between plasma C5 levels and VTE risk displayed a threshold effect, where subjects with C5 levels above the lowest tertile had increased risk of VTE. Subjects in tertile 3 (highest C5 levels) had an age- and sex-adjusted OR of 1.45 (95% CI, 1.07-1.96) compared with tertile 1 (lowest). These statistics were more pronounced for unprovoked VTE (OR, 1.70; 95% CI, 1.11-2.60). Adjustments for body mass index and CRP had minor impact on risk estimates. The OR increased substantially with shorter time between blood sampling and VTE event. In conclusion, plasma C5 was associated with risk of future VTE. C5 levels were not genetically regulated and were only slightly influenced by chronic inflammation. |
format |
Article in Journal/Newspaper |
author |
Skjeflo, Espen Waage Brækkan, Sigrid Kufaas Ludviksen, Judith K Snir, Omri Hindberg, Kristian Mollnes, Tom Eirik Hansen, John-Bjarne |
spellingShingle |
Skjeflo, Espen Waage Brækkan, Sigrid Kufaas Ludviksen, Judith K Snir, Omri Hindberg, Kristian Mollnes, Tom Eirik Hansen, John-Bjarne Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism |
author_facet |
Skjeflo, Espen Waage Brækkan, Sigrid Kufaas Ludviksen, Judith K Snir, Omri Hindberg, Kristian Mollnes, Tom Eirik Hansen, John-Bjarne |
author_sort |
Skjeflo, Espen Waage |
title |
Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism |
title_short |
Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism |
title_full |
Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism |
title_fullStr |
Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism |
title_full_unstemmed |
Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism |
title_sort |
elevated plasma concentration of complement factor c5 is associated with risk of future venous thromboembolism |
publisher |
American Society of Hematology |
publishDate |
2021 |
url |
https://hdl.handle.net/10037/24058 https://doi.org/10.1182/blood.2021010822 |
long_lat |
ENVELOPE(19.361,19.361,70.084,70.084) |
geographic |
Mollnes Tromsø |
geographic_facet |
Mollnes Tromsø |
genre |
Tromsø |
genre_facet |
Tromsø |
op_relation |
Blood Skjeflo EW, Brækkan, Ludviksen JK, Snir, Hindberg, Mollnes, Hansen. Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism. Blood. 2021;138(21):2129-2137 FRIDAID 1963584 doi:10.1182/blood.2021010822 0006-4971 1528-0020 https://hdl.handle.net/10037/24058 |
op_rights |
embargoedAccess Copyright 2021 The Author(s) |
op_doi |
https://doi.org/10.1182/blood.2021010822 |
container_title |
Blood |
container_volume |
138 |
container_issue |
21 |
container_start_page |
2129 |
op_container_end_page |
2137 |
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1766219853173096448 |