Genetically Low Antioxidant Protection and Risk of Cardiovascular Disease and Heart Failure in Diabetic Subjects

Camilla J Kobylecki; Shoaib Afzal; Børge G Nordestgaard

doi:10.1016/j.ebiom.2015.11.026

Genetically Low Antioxidant Protection and Risk of Cardiovascular Disease and Heart Failure in Diabetic Subjects

Camilla J Kobylecki, Shoaib Afzal, Børge G Nordestgaard

Department of Clinical Medicine

14 Citations (Scopus)

Abstract

Background: Hyperglycemia-induced oxidative stress is one mechanism believed to underlie diabetic vascular disease. We tested the hypothesis that diabetic subjects heterozygous for extracellular superoxide dismutase (SOD3) R213G, which entails lower antioxidant capacity in tissues, have increased risk of cardiovascular disease and heart failure. Methods: We used the prospective Copenhagen General Population Study and Copenhagen City Heart Study and genotyped 95,871 individuals for the rs1799895 R213G variation in the SOD3 gene, of which 4498 had diabetes. We used national hospitalization and death registers to assess cardiovascular disease and heart failure. Findings: Out of 95,871 individuals, we identified 93,521 R213G non-carriers (213RR, 97.5%), 2336 heterozygotes (213RG, 2.4%) and 14 homozygotes (213GG, 0.01%). In diabetic subjects, the hazard ratio for cardiovascular disease in R213G heterozygotes compared to non-carriers was 2.32 (95% CI 1·44-3.75), with a corresponding hazard ratio in non-diabetic subjects of 0.97 (0·80-1.19) (p for interaction 0.002). For heart failure, the hazard ratios in R213G heterozygotes compared to non-carriers were 2.19 (1.28-3.76) in diabetic and 0.68 (0.49-0.92) in non-diabetic subjects (p for interaction < 0.001). Interpretation: Risk of cardiovascular disease and heart failure was higher in R213G heterozygotes versus non-carriers in diabetic subjects, but not in non-diabetic subjects.

Original language	English
Journal	EBioMedicine
Volume	2
Issue number	12
Pages (from-to)	2010-5
Number of pages	6
ISSN	2352-3964
DOIs	https://doi.org/10.1016/j.ebiom.2015.11.026
Publication status	Published - 1 Dec 2015

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title = "Genetically Low Antioxidant Protection and Risk of Cardiovascular Disease and Heart Failure in Diabetic Subjects",

abstract = "Background: Hyperglycemia-induced oxidative stress is one mechanism believed to underlie diabetic vascular disease. We tested the hypothesis that diabetic subjects heterozygous for extracellular superoxide dismutase (SOD3) R213G, which entails lower antioxidant capacity in tissues, have increased risk of cardiovascular disease and heart failure. Methods: We used the prospective Copenhagen General Population Study and Copenhagen City Heart Study and genotyped 95,871 individuals for the rs1799895 R213G variation in the SOD3 gene, of which 4498 had diabetes. We used national hospitalization and death registers to assess cardiovascular disease and heart failure. Findings: Out of 95,871 individuals, we identified 93,521 R213G non-carriers (213RR, 97.5%), 2336 heterozygotes (213RG, 2.4%) and 14 homozygotes (213GG, 0.01%). In diabetic subjects, the hazard ratio for cardiovascular disease in R213G heterozygotes compared to non-carriers was 2.32 (95% CI 1·44-3.75), with a corresponding hazard ratio in non-diabetic subjects of 0.97 (0·80-1.19) (p for interaction 0.002). For heart failure, the hazard ratios in R213G heterozygotes compared to non-carriers were 2.19 (1.28-3.76) in diabetic and 0.68 (0.49-0.92) in non-diabetic subjects (p for interaction < 0.001). Interpretation: Risk of cardiovascular disease and heart failure was higher in R213G heterozygotes versus non-carriers in diabetic subjects, but not in non-diabetic subjects.",

author = "Kobylecki, {Camilla J} and Shoaib Afzal and Nordestgaard, {B{\o}rge G}",

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AU - Kobylecki, Camilla J

AU - Afzal, Shoaib

AU - Nordestgaard, Børge G

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Background: Hyperglycemia-induced oxidative stress is one mechanism believed to underlie diabetic vascular disease. We tested the hypothesis that diabetic subjects heterozygous for extracellular superoxide dismutase (SOD3) R213G, which entails lower antioxidant capacity in tissues, have increased risk of cardiovascular disease and heart failure. Methods: We used the prospective Copenhagen General Population Study and Copenhagen City Heart Study and genotyped 95,871 individuals for the rs1799895 R213G variation in the SOD3 gene, of which 4498 had diabetes. We used national hospitalization and death registers to assess cardiovascular disease and heart failure. Findings: Out of 95,871 individuals, we identified 93,521 R213G non-carriers (213RR, 97.5%), 2336 heterozygotes (213RG, 2.4%) and 14 homozygotes (213GG, 0.01%). In diabetic subjects, the hazard ratio for cardiovascular disease in R213G heterozygotes compared to non-carriers was 2.32 (95% CI 1·44-3.75), with a corresponding hazard ratio in non-diabetic subjects of 0.97 (0·80-1.19) (p for interaction 0.002). For heart failure, the hazard ratios in R213G heterozygotes compared to non-carriers were 2.19 (1.28-3.76) in diabetic and 0.68 (0.49-0.92) in non-diabetic subjects (p for interaction < 0.001). Interpretation: Risk of cardiovascular disease and heart failure was higher in R213G heterozygotes versus non-carriers in diabetic subjects, but not in non-diabetic subjects.

AB - Background: Hyperglycemia-induced oxidative stress is one mechanism believed to underlie diabetic vascular disease. We tested the hypothesis that diabetic subjects heterozygous for extracellular superoxide dismutase (SOD3) R213G, which entails lower antioxidant capacity in tissues, have increased risk of cardiovascular disease and heart failure. Methods: We used the prospective Copenhagen General Population Study and Copenhagen City Heart Study and genotyped 95,871 individuals for the rs1799895 R213G variation in the SOD3 gene, of which 4498 had diabetes. We used national hospitalization and death registers to assess cardiovascular disease and heart failure. Findings: Out of 95,871 individuals, we identified 93,521 R213G non-carriers (213RR, 97.5%), 2336 heterozygotes (213RG, 2.4%) and 14 homozygotes (213GG, 0.01%). In diabetic subjects, the hazard ratio for cardiovascular disease in R213G heterozygotes compared to non-carriers was 2.32 (95% CI 1·44-3.75), with a corresponding hazard ratio in non-diabetic subjects of 0.97 (0·80-1.19) (p for interaction 0.002). For heart failure, the hazard ratios in R213G heterozygotes compared to non-carriers were 2.19 (1.28-3.76) in diabetic and 0.68 (0.49-0.92) in non-diabetic subjects (p for interaction < 0.001). Interpretation: Risk of cardiovascular disease and heart failure was higher in R213G heterozygotes versus non-carriers in diabetic subjects, but not in non-diabetic subjects.

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DO - 10.1016/j.ebiom.2015.11.026

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SP - 2010

EP - 2015

JO - EBioMedicine

JF - EBioMedicine

IS - 12

ER -

Genetically Low Antioxidant Protection and Risk of Cardiovascular Disease and Heart Failure in Diabetic Subjects

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