Fibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals
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 = ...
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| Published in | Scientific reports Vol. 11; no. 1; pp. 4605 - 10 |
|---|---|
| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
25.02.2021
Nature Publishing Group Nature Portfolio |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2045-2322 2045-2322 |
| DOI | 10.1038/s41598-021-84046-7 |
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| 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. |
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| AbstractList | 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.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. 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. 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. 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. |
| ArticleNumber | 4605 |
| Author | Poppe, Katrina K. Frampton, Christopher M. A. von Zychlinski, Anne Andersson Överström, Elin Cameron, Vicky A. Lassé, Moritz Kleffmann, Torsten Prickett, Timothy C. R. Pemberton, Christopher J. Lewis, Lynley K. Troughton, Richard W. Pilbrow, Anna P. Richards, Arthur M. |
| Author_xml | – sequence: 1 givenname: Moritz surname: Lassé fullname: Lassé, Moritz email: moritz.lasse@otago.ac.nz organization: Department of Medicine, Christchurch Heart Institute, University of Otago – sequence: 2 givenname: Anna P. surname: Pilbrow fullname: Pilbrow, Anna P. organization: Department of Medicine, Christchurch Heart Institute, University of Otago – sequence: 3 givenname: Torsten surname: Kleffmann fullname: Kleffmann, Torsten organization: Department of Biochemistry, University of Otago – sequence: 4 givenname: Elin surname: Andersson Överström fullname: Andersson Överström, Elin organization: Department of Medicine, Christchurch Heart Institute, University of Otago – sequence: 5 givenname: Anne surname: von Zychlinski fullname: von Zychlinski, Anne organization: Southern Community Laboratories Ltd – sequence: 6 givenname: Christopher M. A. surname: Frampton fullname: Frampton, Christopher M. A. organization: Department of Medicine, Christchurch Heart Institute, University of Otago – sequence: 7 givenname: Katrina K. surname: Poppe fullname: Poppe, Katrina K. organization: School of Population Health, Faculty of Medical and Health Sciences, University of Auckland – sequence: 8 givenname: Richard W. surname: Troughton fullname: Troughton, Richard W. organization: Department of Medicine, Christchurch Heart Institute, University of Otago – sequence: 9 givenname: Lynley K. surname: Lewis fullname: Lewis, Lynley K. organization: Department of Medicine, Christchurch Heart Institute, University of Otago – sequence: 10 givenname: Timothy C. R. surname: Prickett fullname: Prickett, Timothy C. R. organization: Department of Medicine, Christchurch Heart Institute, University of Otago – sequence: 11 givenname: Christopher J. surname: Pemberton fullname: Pemberton, Christopher J. organization: Department of Medicine, Christchurch Heart Institute, University of Otago – sequence: 12 givenname: Arthur M. surname: Richards fullname: Richards, Arthur M. organization: Department of Medicine, Christchurch Heart Institute, University of Otago, Cardiovascular Research Institute, National University of Singapore – sequence: 13 givenname: Vicky A. surname: Cameron fullname: Cameron, Vicky A. organization: Department of Medicine, Christchurch Heart Institute, University of Otago |
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| SubjectTerms | 631/1647/2067 631/1647/664/1467 631/45 692/4019 692/499 692/53 Asymptomatic Cardiovascular diseases Clusterin Complement component C9 Fibrinogen Fibronectin Health risks Hemoglobin Humanities and Social Sciences Lipopolysaccharide-binding protein Lipopolysaccharides Mass spectrometry Mass spectroscopy multidisciplinary Plasma proteins Proteins Science Science (multidisciplinary) |
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| Title | Fibrinogen and hemoglobin predict near future cardiovascular events in asymptomatic individuals |
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