Fibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals

Abstract To identify circulating proteins predictive of acute cardiovascular disease events in the general population, we performed a proteomic screen in plasma from asymptomatic individuals. A “Discovery cohort” of 25 individuals who subsequently incurred a cardiovascular event within 3 years (medi...

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Autores principales: Moritz Lassé, Anna P. Pilbrow, Torsten Kleffmann, Elin Andersson Överström, Anne von Zychlinski, Christopher M. A. Frampton, Katrina K. Poppe, Richard W. Troughton, Lynley K. Lewis, Timothy C. R. Prickett, Christopher J. Pemberton, Arthur M. Richards, Vicky A. Cameron
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/043710be91bb407197c17d86d6c4b4e8
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spelling oai:doaj.org-article:043710be91bb407197c17d86d6c4b4e82021-12-02T13:20:22ZFibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals10.1038/s41598-021-84046-72045-2322https://doaj.org/article/043710be91bb407197c17d86d6c4b4e82021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84046-7https://doaj.org/toc/2045-2322Abstract To identify circulating proteins predictive of acute cardiovascular disease events in the general population, we performed a proteomic screen in plasma from asymptomatic individuals. A “Discovery cohort” of 25 individuals who subsequently incurred a cardiovascular event within 3 years (median age = 70 years, 80% male) was matched to 25 controls remaining event-free for > 5 years (median age = 72 years, 80% male). Plasma proteins were assessed by data independent acquisition mass spectrometry (DIA-MS). Associations with cardiovascular events were tested using Cox regression, adjusted for the New Zealand Cardiovascular Risk Score. Concentrations of leading protein candidates were subsequently measured with ELISAs in a larger (n = 151) independent subset. In the Discovery cohort, 76 plasma proteins were robustly quantified by DIA-MS, with 8 independently associated with cardiovascular events. These included (HR = hazard ratio [95% confidence interval] above vs below median): fibrinogen alpha chain (HR = 1.84 [1.19–2.84]); alpha-2-HS-glycoprotein (also called fetuin A) (HR = 1.86 [1.19–2.93]); clusterin isoform 2 (HR = 1.59 [1.06–2.38]); fibrinogen beta chain (HR = 1.55 [1.04–2.30]); hemoglobin subunit beta (HR = 1.49 [1.04–2.15]); complement component C9 (HR = 1.62 [1.01–2.59]), fibronectin isoform 3 (HR = 0.60 [0.37–0.99]); and lipopolysaccharide-binding protein (HR = 1.58 [1.00–2.49]). The proteins for which DIA-MS and ELISA data were correlated, fibrinogen and hemoglobin, were analyzed in an Extended cohort, with broader inclusion criteria and longer time to events, in which these two proteins were not associated with incident cardiovascular events. We have identified eight candidate proteins that may independently predict cardiovascular events occurring within three years in asymptomatic, low-to-moderate risk individuals, although these appear not to predict events beyond three years.Moritz LasséAnna P. PilbrowTorsten KleffmannElin Andersson ÖverströmAnne von ZychlinskiChristopher M. A. FramptonKatrina K. PoppeRichard W. TroughtonLynley K. LewisTimothy C. R. PrickettChristopher J. PembertonArthur M. RichardsVicky A. CameronNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Moritz Lassé
Anna P. Pilbrow
Torsten Kleffmann
Elin Andersson Överström
Anne von Zychlinski
Christopher M. A. Frampton
Katrina K. Poppe
Richard W. Troughton
Lynley K. Lewis
Timothy C. R. Prickett
Christopher J. Pemberton
Arthur M. Richards
Vicky A. Cameron
Fibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals
description Abstract To identify circulating proteins predictive of acute cardiovascular disease events in the general population, we performed a proteomic screen in plasma from asymptomatic individuals. A “Discovery cohort” of 25 individuals who subsequently incurred a cardiovascular event within 3 years (median age = 70 years, 80% male) was matched to 25 controls remaining event-free for > 5 years (median age = 72 years, 80% male). Plasma proteins were assessed by data independent acquisition mass spectrometry (DIA-MS). Associations with cardiovascular events were tested using Cox regression, adjusted for the New Zealand Cardiovascular Risk Score. Concentrations of leading protein candidates were subsequently measured with ELISAs in a larger (n = 151) independent subset. In the Discovery cohort, 76 plasma proteins were robustly quantified by DIA-MS, with 8 independently associated with cardiovascular events. These included (HR = hazard ratio [95% confidence interval] above vs below median): fibrinogen alpha chain (HR = 1.84 [1.19–2.84]); alpha-2-HS-glycoprotein (also called fetuin A) (HR = 1.86 [1.19–2.93]); clusterin isoform 2 (HR = 1.59 [1.06–2.38]); fibrinogen beta chain (HR = 1.55 [1.04–2.30]); hemoglobin subunit beta (HR = 1.49 [1.04–2.15]); complement component C9 (HR = 1.62 [1.01–2.59]), fibronectin isoform 3 (HR = 0.60 [0.37–0.99]); and lipopolysaccharide-binding protein (HR = 1.58 [1.00–2.49]). The proteins for which DIA-MS and ELISA data were correlated, fibrinogen and hemoglobin, were analyzed in an Extended cohort, with broader inclusion criteria and longer time to events, in which these two proteins were not associated with incident cardiovascular events. We have identified eight candidate proteins that may independently predict cardiovascular events occurring within three years in asymptomatic, low-to-moderate risk individuals, although these appear not to predict events beyond three years.
format article
author Moritz Lassé
Anna P. Pilbrow
Torsten Kleffmann
Elin Andersson Överström
Anne von Zychlinski
Christopher M. A. Frampton
Katrina K. Poppe
Richard W. Troughton
Lynley K. Lewis
Timothy C. R. Prickett
Christopher J. Pemberton
Arthur M. Richards
Vicky A. Cameron
author_facet Moritz Lassé
Anna P. Pilbrow
Torsten Kleffmann
Elin Andersson Överström
Anne von Zychlinski
Christopher M. A. Frampton
Katrina K. Poppe
Richard W. Troughton
Lynley K. Lewis
Timothy C. R. Prickett
Christopher J. Pemberton
Arthur M. Richards
Vicky A. Cameron
author_sort Moritz Lassé
title Fibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals
title_short Fibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals
title_full Fibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals
title_fullStr Fibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals
title_full_unstemmed Fibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals
title_sort fibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/043710be91bb407197c17d86d6c4b4e8
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