Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial
Background 8‐Oxo‐2′‐deoxyguanosine (8‐oxo‐2′‐dG) is a biomarker of oxidative DNA damage that is associated with cardiovascular disease and premature mortality in the general population. Although oxidative stress has a proven role in cardiovascular complications in diabetes mellitus, evidence for a r...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2018-07-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.117.008226 |
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| author | Merlin C. Thomas Mark Woodward Qiang Li Raelene Pickering Christos Tikellis Neil Poulter Mark E. Cooper Michel Marre Sophia Zoungas John Chalmers |
| author_facet | Merlin C. Thomas Mark Woodward Qiang Li Raelene Pickering Christos Tikellis Neil Poulter Mark E. Cooper Michel Marre Sophia Zoungas John Chalmers |
| author_sort | Merlin C. Thomas |
| collection | DOAJ |
| description | Background 8‐Oxo‐2′‐deoxyguanosine (8‐oxo‐2′‐dG) is a biomarker of oxidative DNA damage that is associated with cardiovascular disease and premature mortality in the general population. Although oxidative stress has a proven role in cardiovascular complications in diabetes mellitus, evidence for a relationship between plasma 8‐oxo‐2′‐dG and major cardiovascular outcomes in diabetes mellitus is weak. Methods and Results A case‐cohort study was performed in 3766 participants with prevalent diabetes mellitus in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) trial (ClinicalTrials.gov number NCT00145925). The hazard ratios for mortality and major acute cardiovascular events were derived using Cox regression models. During a median of 5 years of follow‐up, 695 (18.4%) participants in this enriched cohort died (including 354 deaths from cardiovascular disease). Individuals with higher levels of 8‐oxo‐2′‐dG were more likely to die. After adjusting for cardiovascular disease risk factors, the hazard ratio for a 1‐SD increase in plasma 8‐oxo‐2′‐dG was 1.10 (95% confidence interval, 1.01–1.20; P=0.03). This was driven by an independent association between plasma 8‐oxo‐2′‐dG and cardiovascular death (hazard ratio, 1.23; 95% confidence interval, 1.10–1.37 [P<0.001]). By contrast, no association was seen between 8‐oxo‐2′‐dG and noncardiovascular disease death (of which cancer was the major single cause). 8‐Oxo‐2′‐dG was also not significantly associated with either nonfatal myocardial infarction or nonfatal stroke. Conclusions In adults with type 2 diabetes mellitus, increased levels of 8‐oxo‐2′‐dG are independently associated with all‐cause mortality and cardiovascular mortality in adults with longstanding type 2 diabetes mellitus who participated in the ADVANCE trial, consistent with the role of oxidative damage in the development and progression of cardiovascular decompensation in diabetes mellitus. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00145925. |
| first_indexed | 2024-12-22T21:50:31Z |
| format | Article |
| id | doaj.art-f5a714ff7137456a88271273954a7d90 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-22T21:50:31Z |
| publishDate | 2018-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-f5a714ff7137456a88271273954a7d902022-12-21T18:11:22ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802018-07-0171310.1161/JAHA.117.008226Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE TrialMerlin C. Thomas0Mark Woodward1Qiang Li2Raelene Pickering3Christos Tikellis4Neil Poulter5Mark E. Cooper6Michel Marre7Sophia Zoungas8John Chalmers9Department of Diabetes Monash University Melbourne AustraliaThe George Institute for Global Health University of NSW Sydney AustraliaThe George Institute for Global Health University of NSW Sydney AustraliaDepartment of Diabetes Monash University Melbourne AustraliaDepartment of Diabetes Monash University Melbourne AustraliaThe International Centre for Circulatory Health National Heart and Lung Institute Imperial College London United KingdomDepartment of Diabetes Monash University Melbourne AustraliaINSERM UMRS 1138 Centre de Recherche des Cordeliers Paris FranceThe George Institute for Global Health University of NSW Sydney AustraliaThe George Institute for Global Health University of NSW Sydney AustraliaBackground 8‐Oxo‐2′‐deoxyguanosine (8‐oxo‐2′‐dG) is a biomarker of oxidative DNA damage that is associated with cardiovascular disease and premature mortality in the general population. Although oxidative stress has a proven role in cardiovascular complications in diabetes mellitus, evidence for a relationship between plasma 8‐oxo‐2′‐dG and major cardiovascular outcomes in diabetes mellitus is weak. Methods and Results A case‐cohort study was performed in 3766 participants with prevalent diabetes mellitus in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) trial (ClinicalTrials.gov number NCT00145925). The hazard ratios for mortality and major acute cardiovascular events were derived using Cox regression models. During a median of 5 years of follow‐up, 695 (18.4%) participants in this enriched cohort died (including 354 deaths from cardiovascular disease). Individuals with higher levels of 8‐oxo‐2′‐dG were more likely to die. After adjusting for cardiovascular disease risk factors, the hazard ratio for a 1‐SD increase in plasma 8‐oxo‐2′‐dG was 1.10 (95% confidence interval, 1.01–1.20; P=0.03). This was driven by an independent association between plasma 8‐oxo‐2′‐dG and cardiovascular death (hazard ratio, 1.23; 95% confidence interval, 1.10–1.37 [P<0.001]). By contrast, no association was seen between 8‐oxo‐2′‐dG and noncardiovascular disease death (of which cancer was the major single cause). 8‐Oxo‐2′‐dG was also not significantly associated with either nonfatal myocardial infarction or nonfatal stroke. Conclusions In adults with type 2 diabetes mellitus, increased levels of 8‐oxo‐2′‐dG are independently associated with all‐cause mortality and cardiovascular mortality in adults with longstanding type 2 diabetes mellitus who participated in the ADVANCE trial, consistent with the role of oxidative damage in the development and progression of cardiovascular decompensation in diabetes mellitus. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00145925.https://www.ahajournals.org/doi/10.1161/JAHA.117.008226cardiovascular outcomesmortalityoxidative stresssurvival analysistype 2 diabetes mellitus |
| spellingShingle | Merlin C. Thomas Mark Woodward Qiang Li Raelene Pickering Christos Tikellis Neil Poulter Mark E. Cooper Michel Marre Sophia Zoungas John Chalmers Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease cardiovascular outcomes mortality oxidative stress survival analysis type 2 diabetes mellitus |
| title | Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial |
| title_full | Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial |
| title_fullStr | Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial |
| title_full_unstemmed | Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial |
| title_short | Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial |
| title_sort | relationship between plasma 8 oh deoxyguanosine and cardiovascular disease and survival in type 2 diabetes mellitus results from the advance trial |
| topic | cardiovascular outcomes mortality oxidative stress survival analysis type 2 diabetes mellitus |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.117.008226 |
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