Laura K Kjær1,2, Vanja Cejvanovic3,2, Trine Henriksen3, Kasper M Petersen3, Torben Hansen4, Oluf Pedersen4, Cramer K Christensen5, Christian Torp-Pedersen6,7, Thomas A Gerds8, Ivan Brandslund9,10, Thomas Mandrup-Poulsen11, Henrik E Poulsen3,2. 1. Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark laura.kofoed.kjaer@regionh.dk. 2. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 3. Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark. 4. Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 5. Department of Internal Medicine and Endocrinology, Lillebaelt Hospital, Vejle, Denmark. 6. Department of Health, Science and Technology, Aalborg University, Aalborg, Denmark. 7. Department of Cardiology and Epidemiology/Biostatistics, Aalborg University Hospital, Aalborg, Denmark. 8. Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark. 9. Department of Clinical Immunology and Biochemistry, Lillebaelt Hospital, Vejle, Denmark. 10. Faculty of Health Science, Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark. 11. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
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.
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.
Authors: Suvanjaa Sivalingam; Emil List Larsen; Daniel H van Raalte; Marcel H A Muskiet; Mark M Smits; Lennart Tonneijck; Jaap A Joles; Bernt Johan von Scholten; Emilie Hein Zobel; Frederik Persson; Trine Henriksen; Lars Jorge Diaz; Tine W Hansen; Henrik Enghusen Poulsen; Peter Rossing Journal: Sci Rep Date: 2021-05-19 Impact factor: 4.379
Authors: Margalida Monserrat-Mesquida; Magdalena Quetglas-Llabrés; Cristina Bouzas; Silvia García; David Mateos; Cristina Gómez; José M Gámez; Henrik E Poulsen; Josep A Tur; Antoni Sureda Journal: Antioxidants (Basel) Date: 2022-07-05