Hypertension is a widespread and significant public health issue that affects over one billion individuals globally [1]. It is a major contributor to cardiovascular disease, including heart failure, coronary artery disease, chronic kidney conditions, and stroke, which significantly raises global morbidity and mortality rates [2, 3]. Epidemiologically, hypertension is associated with a heavy burden on healthcare systems, as it often leads to life-threatening complications when left uncontrolled [4]. Oxidative stress refers to an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them through antioxidant systems [5]. This imbalance plays a crucial role in developing hypertension and its associated complications [6, 7, 8]. This imbalance contributes to endothelial dysfunction [9], arterial stiffness, and vascular inflammation [10, 11], all of which promote the development and progression of hypertension. A comprehensive understanding of the mechanisms underlying oxidative stress is essential for elucidating its role in hypertension and for the development of targeted therapeutic strategies.

The Oxidative Balance Score (OBS) is an innovative measure designed to assess overall oxidative stress by combining pro-oxidant and antioxidant factors [12]. This metric takes into account various aspects, such as dietary intake, lifestyle behaviors, and specific biochemical indicators to determine an individual’s oxidative profile [13]. Higher OBS values generally indicate greater antioxidant exposure and a healthier redox state, while lower values suggest heightened oxidative burden due to increased pro-oxidant exposure [14]. Although oxidative stress has been extensively studied in chronic diseases [15, 16, 17, 18], few studies link OBS to mortality in those with hypertension. This research addresses that gap by investigating how OBS relates to mortality among hypertensive patients. The findings could enhance our understanding of oxidative balance, guide future interventions, improve hypertension management, and ultimately lead to better patient outcomes.

The study found that among participants with hypertension, there was a significant protective link between higher OBS and lower rates of both all-cause and cardiovascular mortality. Elevated OBS values reflect greater antioxidant exposure and reduced oxidative stress, which correlates with a lower risk of mortality. Subgroup analysis revealed a particularly strong inverse association for non-Hispanic whites, highly educated, and non-diabetic individuals. The study emphasizes oxidative stress as a key contributor to the progression of hypertension and related comorbidities, suggesting that an antioxidant-focused diet and lifestyle could yield better health outcomes for hypertensive patients.

Considerable research has focused on the association between oxidative stress and hypertension [19, 20, 21]. Higher OBS levels correlate with a reduced risk of developing hypertension [22], underscoring the importance of an antioxidant-rich diet and healthy lifestyle for prevention. Additionally, antioxidant supplementation has been shown to improve arterial stiffness and endothelial function in hypertensive patients [8], indicating its potential therapeutic role. Studies have also found that hypertension induced by salt and fructose is linked to inflammatory responses triggered by ROS and free radicals [23], while antioxidant-rich substances such as green tea can effectively lower blood pressure and improve cardiovascular function [24]. Dietary nitrates have been shown to alleviate oxidative stress and inflammation, and traditional herbal formulas, such as Tianma Gouteng Decoction, have demonstrated the ability to reverse hypertension-related cardiovascular remodeling by regulating oxidative stress and inflammation [25]. Collectively, these findings suggest that oxidative stress is a crucial driver of hypertension pathology and a potential treatment target. Improving outcomes may be possible by regulating oxidative balance.

At the molecular and cellular levels, oxidative stress plays a vital role in initiating and progression of cardiovascular diseases. Excessive production of free radicals, particularly ROS, leads to lipid peroxidation, protein modification, and DNA damage, which trigger inflammatory responses and cell apoptosis [26]. For example, oxidized low-density lipoprotein (ox-LDL) is a key contributor to early atherosclerosis, promoting arterial plaque formation by increasing macrophage uptake and foam cell formation [27]. Oxidative stress also contributes to endothelial dysfunction and vasoconstriction through the inactivation of tetrahydrobiopterin (BH4), leading to dysregulation of endothelial nitric oxide synthase (eNOS) [28]. Furthermore, recent studies have shown that oxidative stress activates multiple inflammatory pathways, including NF-$\kappa$B, the NOD-like receptor protein 3 (NLRP3) inflammasome, and NADPH oxidase (NOX) [29, 30]. These pathways intensify vascular inflammation and accelerate the progression of atherosclerosis, further underscoring the detrimental impact of oxidative stress in cardiovascular pathology [31, 32].

Individuals with higher OBS scores typically exhibit greater intake of dietary antioxidants, including polyphenols, flavonoids, and vitamins C and E, which can directly or indirectly neutralize free radicals and inhibit inflammatory pathways related to oxidative stress. Additionally, those with higher OBS are likely to have lower exposure to pro-oxidative factors such as smoking, alcohol use, and high-fat diets, which may contribute to the observed reduction in mortality risk. Unlike conventional biomarkers such as thiobarbituric acid-reactive substances (TBARS), superoxide dismutase (SOD), and glutathione peroxidase (GSHPx)—which reflect short-term oxidative changes, require invasive sampling, and are difficult to standardize in large populations—OBS offers a non-invasive, stable, and integrative measure of long-term oxidative balance. By combining dietary and lifestyle factors, OBS captures cumulative oxidative stress exposure, making it a more practical and informative tool for studying chronic diseases like hypertension in large-scale epidemiology.

Consistent with prior investigations, this study reinforces the adverse cardiovascular effects of oxidative stress and suggests that a higher OBS may offer protective benefits for individuals with hypertension. This study also highlights that this protective effect is more pronounced in certain subgroups, emphasizing the critical role of antioxidant status in the prognosis of hypertension patients.

Several limitations should be taken into consideration in this study. First, the OBS is derived from self-reported dietary and lifestyle data, which may not accurately reflect long-term changes. Second, the observational design limits the ability to establish a causal relationship between OBS and mortality outcomes. Third, the generalizability of the findings may be restricted, as the cohort was drawn from a U.S. representative sample, which may not apply to populations with differing dietary habits, healthcare systems, or genetic backgrounds. Fourth, while OBS measures oxidative balance, it may not fully encompass all sources of oxidative stress or the complex biological interactions among various antioxidant components. Furthermore, the exclusion of participants with missing critical variables could introduce selection bias, thereby compromising the representativeness of the final analytic sample and potentially resulting in either an underestimation or overestimation of the observed associations.

Despite these limitations, the investigation underscores the potential for oxidative balance to reduce mortality risk among hypertensive patients. Future research should focus on longitudinal studies to track the long-term health effects of OBS, as well as intervention trials to determine whether lifestyle modifications can raise OBS and improve clinical outcomes. Additionally, further exploration of the underlying biological processes is warranted.

In conclusion, this study demonstrates an association between higher OBS levels and reduced all-cause and cardiovascular mortality among adults with hypertension. These findings underscore the importance of maintaining oxidative balance as a potential component for hypertension management and highlight the possible benefits of an antioxidant-rich dietary lifestyle for individuals living with this condition.

OBS, Oxidative Balance Score; NHANES, National Health and Nutrition Examination Survey; NCHS, National Center for Health Statistics; PIR, poverty-to-income ratio; K-M, Kaplan-Meier; RCS, restricted cubic splines; ROS, reactive oxygen species; ox-LDL, oxidized low-density lipoprotein; BH4, tetrahydrobiopterin; eNOS, endothelial nitric oxide synthase; NOX, NADPH oxidase; TBARS, thiobarbituric acid-reactive substances; SOD, superoxide dismutase; GSHPx, glutathione peroxidase.

This study’s data are publicly available at the National Center for Health Statistics (https://wwwn.cdc.gov/nchs/nhanes).

LF and YLH conceived and designed the research. BH and XH conducted data analyses and drafted the manuscript. YXS was responsible for data management and methodology development. TL and FL performed data analyses and software operations. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

The public database received Institutional Review Board approval from the National Center for Health Statistics, and all participants consented to the survey. No further IRB approval was needed for the secondary analyses.

This work was funded by the Outstanding Young Medical Staff in Guangdong Province (600001), Scientific Research Start Plan of the Eighth Affiliated Hospital, Southern Medical University (SRSP2024004), and the Clinical Research Startup Program of the Eighth Affiliated Hospital, Southern Medical University (CRSP2019001).

The authors declare no conflict of interest.

Supplementary material associated with this article can be found, in the online version, at https://doi.org/10.31083/RCM37415.