Biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons.

<h4>Background</h4>Early identification of ambulatory persons at high short-term risk of death could benefit targeted prevention. To identify biomarkers for all-cause mortality and enhance risk prediction, we conducted high-throughput profiling of blood specimens in two large population-...

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Autores principales: Krista Fischer, Johannes Kettunen, Peter Würtz, Toomas Haller, Aki S Havulinna, Antti J Kangas, Pasi Soininen, Tõnu Esko, Mari-Liis Tammesoo, Reedik Mägi, Steven Smit, Aarno Palotie, Samuli Ripatti, Veikko Salomaa, Mika Ala-Korpela, Markus Perola, Andres Metspalu
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spelling oai:doaj.org-article:6a872e0ae49e4ad9a2500c9c8ff199a12021-11-18T05:42:57ZBiomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons.1549-12771549-167610.1371/journal.pmed.1001606https://doaj.org/article/6a872e0ae49e4ad9a2500c9c8ff199a12014-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586121/?tool=EBIhttps://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>Early identification of ambulatory persons at high short-term risk of death could benefit targeted prevention. To identify biomarkers for all-cause mortality and enhance risk prediction, we conducted high-throughput profiling of blood specimens in two large population-based cohorts.<h4>Methods and findings</h4>106 candidate biomarkers were quantified by nuclear magnetic resonance spectroscopy of non-fasting plasma samples from a random subset of the Estonian Biobank (n = 9,842; age range 18-103 y; 508 deaths during a median of 5.4 y of follow-up). Biomarkers for all-cause mortality were examined using stepwise proportional hazards models. Significant biomarkers were validated and incremental predictive utility assessed in a population-based cohort from Finland (n = 7,503; 176 deaths during 5 y of follow-up). Four circulating biomarkers predicted the risk of all-cause mortality among participants from the Estonian Biobank after adjusting for conventional risk factors: alpha-1-acid glycoprotein (hazard ratio [HR] 1.67 per 1-standard deviation increment, 95% CI 1.53-1.82, p = 5×10⁻³¹), albumin (HR 0.70, 95% CI 0.65-0.76, p = 2×10⁻¹⁸), very-low-density lipoprotein particle size (HR 0.69, 95% CI 0.62-0.77, p = 3×10⁻¹²), and citrate (HR 1.33, 95% CI 1.21-1.45, p = 5×10⁻¹⁰). All four biomarkers were predictive of cardiovascular mortality, as well as death from cancer and other nonvascular diseases. One in five participants in the Estonian Biobank cohort with a biomarker summary score within the highest percentile died during the first year of follow-up, indicating prominent systemic reflections of frailty. The biomarker associations all replicated in the Finnish validation cohort. Including the four biomarkers in a risk prediction score improved risk assessment for 5-y mortality (increase in C-statistics 0.031, p = 0.01; continuous reclassification improvement 26.3%, p = 0.001).<h4>Conclusions</h4>Biomarker associations with cardiovascular, nonvascular, and cancer mortality suggest novel systemic connectivities across seemingly disparate morbidities. The biomarker profiling improved prediction of the short-term risk of death from all causes above established risk factors. Further investigations are needed to clarify the biological mechanisms and the utility of these biomarkers for guiding screening and prevention.Krista FischerJohannes KettunenPeter WürtzToomas HallerAki S HavulinnaAntti J KangasPasi SoininenTõnu EskoMari-Liis TammesooReedik MägiSteven SmitAarno PalotieSamuli RipattiVeikko SalomaaMika Ala-KorpelaMarkus PerolaAndres MetspaluPublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 11, Iss 2, p e1001606 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
spellingShingle Medicine
R
Krista Fischer
Johannes Kettunen
Peter Würtz
Toomas Haller
Aki S Havulinna
Antti J Kangas
Pasi Soininen
Tõnu Esko
Mari-Liis Tammesoo
Reedik Mägi
Steven Smit
Aarno Palotie
Samuli Ripatti
Veikko Salomaa
Mika Ala-Korpela
Markus Perola
Andres Metspalu
Biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons.
description <h4>Background</h4>Early identification of ambulatory persons at high short-term risk of death could benefit targeted prevention. To identify biomarkers for all-cause mortality and enhance risk prediction, we conducted high-throughput profiling of blood specimens in two large population-based cohorts.<h4>Methods and findings</h4>106 candidate biomarkers were quantified by nuclear magnetic resonance spectroscopy of non-fasting plasma samples from a random subset of the Estonian Biobank (n = 9,842; age range 18-103 y; 508 deaths during a median of 5.4 y of follow-up). Biomarkers for all-cause mortality were examined using stepwise proportional hazards models. Significant biomarkers were validated and incremental predictive utility assessed in a population-based cohort from Finland (n = 7,503; 176 deaths during 5 y of follow-up). Four circulating biomarkers predicted the risk of all-cause mortality among participants from the Estonian Biobank after adjusting for conventional risk factors: alpha-1-acid glycoprotein (hazard ratio [HR] 1.67 per 1-standard deviation increment, 95% CI 1.53-1.82, p = 5×10⁻³¹), albumin (HR 0.70, 95% CI 0.65-0.76, p = 2×10⁻¹⁸), very-low-density lipoprotein particle size (HR 0.69, 95% CI 0.62-0.77, p = 3×10⁻¹²), and citrate (HR 1.33, 95% CI 1.21-1.45, p = 5×10⁻¹⁰). All four biomarkers were predictive of cardiovascular mortality, as well as death from cancer and other nonvascular diseases. One in five participants in the Estonian Biobank cohort with a biomarker summary score within the highest percentile died during the first year of follow-up, indicating prominent systemic reflections of frailty. The biomarker associations all replicated in the Finnish validation cohort. Including the four biomarkers in a risk prediction score improved risk assessment for 5-y mortality (increase in C-statistics 0.031, p = 0.01; continuous reclassification improvement 26.3%, p = 0.001).<h4>Conclusions</h4>Biomarker associations with cardiovascular, nonvascular, and cancer mortality suggest novel systemic connectivities across seemingly disparate morbidities. The biomarker profiling improved prediction of the short-term risk of death from all causes above established risk factors. Further investigations are needed to clarify the biological mechanisms and the utility of these biomarkers for guiding screening and prevention.
format article
author Krista Fischer
Johannes Kettunen
Peter Würtz
Toomas Haller
Aki S Havulinna
Antti J Kangas
Pasi Soininen
Tõnu Esko
Mari-Liis Tammesoo
Reedik Mägi
Steven Smit
Aarno Palotie
Samuli Ripatti
Veikko Salomaa
Mika Ala-Korpela
Markus Perola
Andres Metspalu
author_facet Krista Fischer
Johannes Kettunen
Peter Würtz
Toomas Haller
Aki S Havulinna
Antti J Kangas
Pasi Soininen
Tõnu Esko
Mari-Liis Tammesoo
Reedik Mägi
Steven Smit
Aarno Palotie
Samuli Ripatti
Veikko Salomaa
Mika Ala-Korpela
Markus Perola
Andres Metspalu
author_sort Krista Fischer
title Biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons.
title_short Biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons.
title_full Biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons.
title_fullStr Biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons.
title_full_unstemmed Biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons.
title_sort biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/6a872e0ae49e4ad9a2500c9c8ff199a1
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