Cardiovascular and All-Cause Mortality Risk Associated With Urinary Excretion of 8-oxoGuo, a Biomarker for RNA Oxidation, in Patients With Type 2 Diabetes

A Prospective Cohort Study

Laura K Kjær, Vanja Cejvanovic, Trine Henriksen, Kasper M Petersen, Torben Hansen, Oluf Pedersen, Cramer K Christensen, Christian Torp-Pedersen, Thomas A Gerds, Ivan Brandslund, Thomas Mandrup-Poulsen, Henrik E Poulsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

OBJECTIVE: Cardiovascular mortality risk remains high among patients with type 2 diabetes. Oxidative stress indicated by high urinary excretion of the biomarker for RNA oxidation, 8-oxo-7,8-dihydroguanosine (8-oxoGuo), is associated with an increased risk of death in newly diagnosed and treated patients. We assessed whether 8-oxoGuo is associated with specific cardiovascular and all-cause mortality risk.

RESEARCH DESIGN AND METHODS: Urinary biomarkers for nucleic acid oxidation were measured in a cohort of patients with type 2 diabetes aged ≥60 years (n = 1,863), along with biochemical measurements, questionnaire findings, and Central Person Registry information to estimate the hazard ratios (HRs) for log2-transformed RNA oxidation using Cox regression.

RESULTS: During the 5-year follow-up, 173 of 1,863 patients had died (9.3%), including 73 patients who died of cardiovascular disease (42.2%). Doubling of RNA oxidation was associated with an HR of all-cause mortality of 2.10 (95% CI 1.63-2.71; P < 0.001) and an HR of cardiovascular death of 1.82 (95% CI 1.20-2.77; P = 0.005) after multiple adjustments. The 5-year absolute risks (ARs) of all-cause mortality (AR 13.9 [95% CI 10.8-17.0] vs. AR 6.10 [95% CI 4.00-8.30]) and cardiovascular mortality (AR 5.49 [95% CI 3.44-7.55] vs. AR 3.16 [95% CI 1.59-4.73]) were approximately two times higher in the highest quartile of RNA oxidation than in the lowest quartile.

CONCLUSIONS: We conclude that high RNA oxidation is associated with all-cause and cardiovascular mortality risk in patients with type 2 diabetes. Targeting oxidative stress via interventions with long-term follow-up may reveal the predictive potential of the biomarker 8-oxoGuo.

Original languageEnglish
JournalDiabetes Care
Volume40
Issue number2
Pages (from-to)1771-1778
ISSN0149-5992
DOIs
Publication statusPublished - 2017

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Type 2 Diabetes Mellitus
Cohort Studies
Prospective Studies
RNA
8-hydroxyguanosine
Nucleic Acids
Registries

Keywords

  • Journal Article

Cite this

Kjær, Laura K ; Cejvanovic, Vanja ; Henriksen, Trine ; Petersen, Kasper M ; Hansen, Torben ; Pedersen, Oluf ; Christensen, Cramer K ; Torp-Pedersen, Christian ; Gerds, Thomas A ; Brandslund, Ivan ; Mandrup-Poulsen, Thomas ; Poulsen, Henrik E. / Cardiovascular and All-Cause Mortality Risk Associated With Urinary Excretion of 8-oxoGuo, a Biomarker for RNA Oxidation, in Patients With Type 2 Diabetes : A Prospective Cohort Study. In: Diabetes Care. 2017 ; Vol. 40, No. 2. pp. 1771-1778.
@article{a825fb8e90a74eb2bc88bf285ab7b718,
title = "Cardiovascular and All-Cause Mortality Risk Associated With Urinary Excretion of 8-oxoGuo, a Biomarker for RNA Oxidation, in Patients With Type 2 Diabetes: A Prospective Cohort Study",
abstract = "OBJECTIVE: Cardiovascular mortality risk remains high among patients with type 2 diabetes. Oxidative stress indicated by high urinary excretion of the biomarker for RNA oxidation, 8-oxo-7,8-dihydroguanosine (8-oxoGuo), is associated with an increased risk of death in newly diagnosed and treated patients. We assessed whether 8-oxoGuo is associated with specific cardiovascular and all-cause mortality risk.RESEARCH DESIGN AND METHODS: Urinary biomarkers for nucleic acid oxidation were measured in a cohort of patients with type 2 diabetes aged ≥60 years (n = 1,863), along with biochemical measurements, questionnaire findings, and Central Person Registry information to estimate the hazard ratios (HRs) for log2-transformed RNA oxidation using Cox regression.RESULTS: During the 5-year follow-up, 173 of 1,863 patients had died (9.3{\%}), including 73 patients who died of cardiovascular disease (42.2{\%}). Doubling of RNA oxidation was associated with an HR of all-cause mortality of 2.10 (95{\%} CI 1.63-2.71; P < 0.001) and an HR of cardiovascular death of 1.82 (95{\%} CI 1.20-2.77; P = 0.005) after multiple adjustments. The 5-year absolute risks (ARs) of all-cause mortality (AR 13.9 [95{\%} CI 10.8-17.0] vs. AR 6.10 [95{\%} CI 4.00-8.30]) and cardiovascular mortality (AR 5.49 [95{\%} CI 3.44-7.55] vs. AR 3.16 [95{\%} CI 1.59-4.73]) were approximately two times higher in the highest quartile of RNA oxidation than in the lowest quartile.CONCLUSIONS: We conclude that high RNA oxidation is associated with all-cause and cardiovascular mortality risk in patients with type 2 diabetes. Targeting oxidative stress via interventions with long-term follow-up may reveal the predictive potential of the biomarker 8-oxoGuo.",
keywords = "Journal Article",
author = "Kj{\ae}r, {Laura K} and Vanja Cejvanovic and Trine Henriksen and Petersen, {Kasper M} and Torben Hansen and Oluf Pedersen and Christensen, {Cramer K} and Christian Torp-Pedersen and Gerds, {Thomas A} and Ivan Brandslund and Thomas Mandrup-Poulsen and Poulsen, {Henrik E}",
note = "{\circledC} 2017 by the American Diabetes Association.",
year = "2017",
doi = "10.2337/dc17-1150",
language = "English",
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pages = "1771--1778",
journal = "Diabetes Care",
issn = "0149-5992",
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Kjær, LK, Cejvanovic, V, Henriksen, T, Petersen, KM, Hansen, T, Pedersen, O, Christensen, CK, Torp-Pedersen, C, Gerds, TA, Brandslund, I, Mandrup-Poulsen, T & Poulsen, HE 2017, 'Cardiovascular and All-Cause Mortality Risk Associated With Urinary Excretion of 8-oxoGuo, a Biomarker for RNA Oxidation, in Patients With Type 2 Diabetes: A Prospective Cohort Study', Diabetes Care, vol. 40, no. 2, pp. 1771-1778. https://doi.org/10.2337/dc17-1150

Cardiovascular and All-Cause Mortality Risk Associated With Urinary Excretion of 8-oxoGuo, a Biomarker for RNA Oxidation, in Patients With Type 2 Diabetes : A Prospective Cohort Study. / Kjær, Laura K; Cejvanovic, Vanja; Henriksen, Trine; Petersen, Kasper M; Hansen, Torben; Pedersen, Oluf; Christensen, Cramer K; Torp-Pedersen, Christian; Gerds, Thomas A; Brandslund, Ivan; Mandrup-Poulsen, Thomas; Poulsen, Henrik E.

In: Diabetes Care, Vol. 40, No. 2, 2017, p. 1771-1778.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Cardiovascular and All-Cause Mortality Risk Associated With Urinary Excretion of 8-oxoGuo, a Biomarker for RNA Oxidation, in Patients With Type 2 Diabetes

T2 - A Prospective Cohort Study

AU - Kjær, Laura K

AU - Cejvanovic, Vanja

AU - Henriksen, Trine

AU - Petersen, Kasper M

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Christensen, Cramer K

AU - Torp-Pedersen, Christian

AU - Gerds, Thomas A

AU - Brandslund, Ivan

AU - Mandrup-Poulsen, Thomas

AU - Poulsen, Henrik E

N1 - © 2017 by the American Diabetes Association.

PY - 2017

Y1 - 2017

N2 - OBJECTIVE: Cardiovascular mortality risk remains high among patients with type 2 diabetes. Oxidative stress indicated by high urinary excretion of the biomarker for RNA oxidation, 8-oxo-7,8-dihydroguanosine (8-oxoGuo), is associated with an increased risk of death in newly diagnosed and treated patients. We assessed whether 8-oxoGuo is associated with specific cardiovascular and all-cause mortality risk.RESEARCH DESIGN AND METHODS: Urinary biomarkers for nucleic acid oxidation were measured in a cohort of patients with type 2 diabetes aged ≥60 years (n = 1,863), along with biochemical measurements, questionnaire findings, and Central Person Registry information to estimate the hazard ratios (HRs) for log2-transformed RNA oxidation using Cox regression.RESULTS: During the 5-year follow-up, 173 of 1,863 patients had died (9.3%), including 73 patients who died of cardiovascular disease (42.2%). Doubling of RNA oxidation was associated with an HR of all-cause mortality of 2.10 (95% CI 1.63-2.71; P < 0.001) and an HR of cardiovascular death of 1.82 (95% CI 1.20-2.77; P = 0.005) after multiple adjustments. The 5-year absolute risks (ARs) of all-cause mortality (AR 13.9 [95% CI 10.8-17.0] vs. AR 6.10 [95% CI 4.00-8.30]) and cardiovascular mortality (AR 5.49 [95% CI 3.44-7.55] vs. AR 3.16 [95% CI 1.59-4.73]) were approximately two times higher in the highest quartile of RNA oxidation than in the lowest quartile.CONCLUSIONS: We conclude that high RNA oxidation is associated with all-cause and cardiovascular mortality risk in patients with type 2 diabetes. Targeting oxidative stress via interventions with long-term follow-up may reveal the predictive potential of the biomarker 8-oxoGuo.

AB - OBJECTIVE: Cardiovascular mortality risk remains high among patients with type 2 diabetes. Oxidative stress indicated by high urinary excretion of the biomarker for RNA oxidation, 8-oxo-7,8-dihydroguanosine (8-oxoGuo), is associated with an increased risk of death in newly diagnosed and treated patients. We assessed whether 8-oxoGuo is associated with specific cardiovascular and all-cause mortality risk.RESEARCH DESIGN AND METHODS: Urinary biomarkers for nucleic acid oxidation were measured in a cohort of patients with type 2 diabetes aged ≥60 years (n = 1,863), along with biochemical measurements, questionnaire findings, and Central Person Registry information to estimate the hazard ratios (HRs) for log2-transformed RNA oxidation using Cox regression.RESULTS: During the 5-year follow-up, 173 of 1,863 patients had died (9.3%), including 73 patients who died of cardiovascular disease (42.2%). Doubling of RNA oxidation was associated with an HR of all-cause mortality of 2.10 (95% CI 1.63-2.71; P < 0.001) and an HR of cardiovascular death of 1.82 (95% CI 1.20-2.77; P = 0.005) after multiple adjustments. The 5-year absolute risks (ARs) of all-cause mortality (AR 13.9 [95% CI 10.8-17.0] vs. AR 6.10 [95% CI 4.00-8.30]) and cardiovascular mortality (AR 5.49 [95% CI 3.44-7.55] vs. AR 3.16 [95% CI 1.59-4.73]) were approximately two times higher in the highest quartile of RNA oxidation than in the lowest quartile.CONCLUSIONS: We conclude that high RNA oxidation is associated with all-cause and cardiovascular mortality risk in patients with type 2 diabetes. Targeting oxidative stress via interventions with long-term follow-up may reveal the predictive potential of the biomarker 8-oxoGuo.

KW - Journal Article

U2 - 10.2337/dc17-1150

DO - 10.2337/dc17-1150

M3 - Journal article

VL - 40

SP - 1771

EP - 1778

JO - Diabetes Care

JF - Diabetes Care

SN - 0149-5992

IS - 2

ER -