Oxidative stress-related genetic variation and antioxidant vitamin intake in intact and ruptured abdominal aortic aneurysm: a Swedish population-based retrospective cohort study.

Anders Gottsäter, Ashfaque A Memon, Sakshi Vats, Jan Sundquist, Kristina Sundquist, Stefan Acosta, Xiao Wang, Naiqi Zhang

Journal: European journal of preventive cardiology 2024;31(1):61-74

PMID: 37665957

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Abstract

AIMS

The aim of this study is to investigate how genetic variations in genes related to oxidative stress, intake of antioxidant vitamins, and any potential interactions between these factors affect the incidence of intact abdominal aortic aneurysm (AAA) and its rupture (rAAA), accounting for sex differences where possible.

METHODS AND RESULTS

The present retrospective cohort study (n = 25 252) uses baseline single-nucleotide polymorphisms (SNPs) and total antioxidant vitamin intake data from the large population-based, Malmö Diet and Cancer Study. Cumulative incidence of intact AAA was 1.6% and of rAAA 0.3% after a median follow-up of 24.3 years. A variant in NOX3 (rs3749930) was associated with higher rAAA risk in males [adjusted hazard ratio (aHR): 2.49; 95% confidence interval (CI): 1.36-4.35] and the overall population (aHR: 1.88; 95% CI: 1.05-3.37). Higher intakes of antioxidant vitamins, riboflavin, and folate were associated with 20% and 19% reduced intact AAA incidence, respectively. Interestingly, the inverse associations between riboflavin and vitamin D intake with intact AAA incidence were stronger in the individuals carrying the NOX3 variant as compared with the wild-type recessive genotype, i.e. by 60% and 66%, respectively (P for interaction < 0.05). Higher riboflavin intake was associated with a 33% male-specific intact AAA risk reduction, while higher intake of vitamin B12 intake was associated with 55% female-specific intact AAA risk increase; both these associations were significantly modified by sex (P for interaction < 0.05).

CONCLUSIONS

Our findings highlight the role of oxidative stress genetic variations and antioxidant vitamin intake in AAA. Although a low AAA/rAAA sample size limited some analyses, especially in females, our findings highlight the need for future randomized controlled trials and mechanistic studies, to explore the potential benefits of antioxidant vitamins while accounting for genetic and sex differences.

Address: Center for Primary Health Care Research, Wallenberg Laboratory, 5th floor, Inga Marie Nilsson's gata 53, 214 28, Malmö, Sweden.; Center for Primary Health Care Research, Department of Clinical Sciences, Lund University/Region Skåne, Malmö, Sweden.; Center for Primary Health Care Research, Department of Clinical Sciences, Lund University/Region Skåne, Malmö, Sweden.; Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, USA.; Center for Community-Based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Matsue, Japan.; Center for Primary Health Care Research, Department of Clinical Sciences, Lund University/Region Skåne, Malmö, Sweden.; Department of Clinical Sciences, Lund University, Malmö, Sweden.; Vascular Centre, Department of Cardiothoracic and Vascular Surgery, Skåne University Hospital, Lund University, Malmö, S-205 02, Sweden.; Vascular Centre, Department of Cardiothoracic and Vascular Surgery, Skåne University Hospital, Lund University, Malmö, S-205 02, Sweden.

DOI: 10.1093/eurjpc/zwad271

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MeSH Terms: Humans, Male, Female, Retrospective Studies, Antioxidants, Sweden, Risk Factors, Aortic Aneurysm, Abdominal, Aortic Rupture, Vitamin A, Oxidative Stress, Vitamins, Riboflavin, Genetic Variation