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REVIEW ARTICLE

Reactive oxygen species imbalance in atherosclerosis: Biomarker phenotyping, residual risk, and a translational framework for precision prevention

Yasser M. Esmaeil1* ,  Marjona Nurillaeva1,2 ,  Aamir Khan1,2 ,  Matthew Wiesner1,2
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1 Department of Internal Medicine, St. John’s Episcopal Hospital, New York City, New York, United States of America
2 Ross University School of Medicine, Bridgetown, Barbados
JCTR, 026250058 https://doi.org/10.36922/JCTR026250058
Received: 18 June 2026 | Revised: 13 July 2026 | Accepted: 20 July 2026 | Published online: 3 August 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Background: Atherosclerotic cardiovascular disease (ASCVD) leaves substantial residual risk despite intensive low-density lipoprotein-cholesterol lowering and anti-inflammatory therapy. Reactive oxygen species (ROS) have long been implicated, yet neutral broad-antioxidant trials left unclear which dimensions of ROS imbalance are causal, clinically informative, and therapeutically tractable. Aim: To critically appraise ROS imbalance in atherosclerosis through a plausibility–association–utility hierarchy and to propose a staged framework for precision cardiovascular prevention. Methods: We synthesized mechanistic, biomarker, and translational evidence from targeted PubMed/MEDLINE, Embase, and Cochrane searches (January 2000–February 2026), combining terms for ROS, oxidative stress, atherosclerosis, oxidative biomarkers, and residual cardiovascular risk, with citation chaining. Mass-spectrometry biomarker work, prospective cohorts, and randomized trials received greater interpretive weight. Systematic-review procedures were not applied. Results: Compartmentalized, source-specific ROS imbalance contributes to endothelial dysfunction, lipoprotein oxidation, inflammatory amplification, and plaque progression, particularly in high-risk cardiometabolic phenotypes. Human biomarker data are predominantly observational, assay standardization is incomplete, and risk-reclassification evidence is limited. F2-isoprostanes are a relatively mature lipid-peroxidation marker better suited to trial enrichment than treatment selection. Conclusion: Oxidative biomarkers are defensibly used for trial enrichment but not individual treatment selection. A staged precision-prevention agenda should test source-selective interventions in biomarker-enriched cohorts using vascular and mechanistic endpoints before large outcome trials. Relevance for Patients: Adults whose cardiovascular risk remains high despite cholesterol-lowering and anti-inflammatory treatment—including those with diabetes, kidney disease, smoking, obesity, or recurrent events—may eventually benefit if oxidative stress tests can identify who remains vulnerable and guide targeted prevention.

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Keywords
Reactive oxygen species
Oxidative stress
Atherosclerosis
F2-isoprostanes
Residual cardiovascular risk
Precision cardiovascular prevention
Biomarkers
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
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