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Author ORCID Identifier

https://orcid.org/0000-0002-4282-3537

Date Available

5-8-2028

Year of Publication

2026

Document Type

Doctoral Dissertation

Degree Name

Doctor of Philosophy (PhD)

College

Nursing

Department/School/Program

Nursing

Faculty

Gia Mudd-Martin

Faculty

Jean Edward

Abstract

Oxidative stress contributes to cardiometabolic diseases (CMD) by several mechanisms, including cellular damage and the release of toxic mediators. However, oxidative stress is influenced by multiple factors, including sex, inflammation, obesity, psychological stress, and depressive symptoms, all of which may adversely affect CMD. The interplay between oxidative stress and these factors has not been adequately elucidated. Therefore, the purpose of this dissertation is to examine factors that may mitigate and contribute to oxidative stress in patients with CMD. The specific aims of this dissertation were to: 1- systematically review the evidence of the effect of antioxidants on oxidative stress in patients with coronary artery disease, 2- test the psychometric properties of the Patient Health Questionnaire-9 (PHQ-9) as a measure of depressive symptoms in patients with heart failure and an implantable cardioverter defibrillator, 3- explore the sex differences in oxidative stress and potential contributing factors, and to examine the relationships between these potential contributing factors and oxidative stress in patients with metabolic syndrome.

This dissertation includes three papers. The first is a systematic review of randomized controlled trials investigating the efficacy of antioxidants in reducing oxidative stress in patients with coronary artery disease. Fifteen studies were included. These studies examined the effects of 14 different antioxidants; among them, 13 antioxidants effectively mitigated oxidative stress; however, the heterogeneity in antioxidant types and oxidative stress measures limited the strength of the evidence. The dose and length of administration varied with two general patterns: administering antioxidants in high doses and short duration intravenously for symptomatic patients, and administering antioxidants in regular doses and long duration as a supplement or dietary modification for asymptomatic patients. The second paper was a secondary analysis of data to test the psychometric properties of the PHQ-9 in patients with heart failure and an implantable cardioverter-defibrillator. The findings revealed that the PHQ-9 is a valid and reliable instrument to screen for depression in this high-risk population. The third paper was a secondary analysis of data from a randomized controlled trial to investigate the sex differences in oxidative stress and to investigate potential contributing factors to oxidative stress, while controlling for age and smoking, in patients with metabolic syndrome. Findings revealed that females are at a higher risk of oxidative stress compared to males. Sex, interleukin-6, tumor necrosis factor-α, C-reactive protein, body mass index, PHQ-9, and psychological stress were significantly associated with oxidative stress measured by malondialdehyde.

The findings of these studies demonstrated that several factors could affect oxidative stress in patients with CMD, and these relationships can be affected by the patient's health status, age, and sex. The findings provide modest evidence that several antioxidants have a beneficial effect on reducing oxidative stress. Also, females and patients with high inflammatory biomarkers are at high risk for oxidative stress. These findings address an important gap in the literature by delineating the factors that are associated with oxidative stress in patients with CMD. The PHQ-9 should be used to screen for depression, which contributes to oxidative stress, in patients with CMD. Future research should further examine factors that mitigate and contribute to oxidative stress across diverse populations, with particular attention to dietary, hormonal, and genetic influences, and should elucidate mechanisms to better manage oxidative stress in high-risk patients using standardized interventions and oxidative stress measures.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2026.33

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