The role of oxidative stress in modulating mortality risk across the hypertension control cascade.

Background: The role of oxidative stress in hypertensive populations has not yet been fully elucidated. This study examines the association between the Oxidative Balance Score (OBS) and all-cause and cardiovascular mortality under different hypertension control cascade outcomes while assessing mediation by low-grade systemic inflammation and multi-organ function.

Methods: This cohort study analyzed 1999-2018 NHANES data, with mortality outcomes from the National Death Index (NDI). It encompassed U.S. adults with hypertension. OBS consists of 20 nutrition and lifestyle factors. Low-grade systemic inflammation (NLR, SIRI) and multi-organ function (eGFR, UACR, FIB-4 index, SUA) were examined as potential mediators. Statistical analyses included Kaplan-Meier analysis, Cox models, restricted cubic splines (RCS), subgroup analyses, and mediation analysis.

Results: Participants in the highest OBS quartile (Q4) exhibited lower all-cause mortality (HR: 0.72; 95% CI: 0.59-0.88; P = 0.001) and cardiovascular mortality (HR: 0.64; 95% CI: 0.42-0.99; P = 0.044) than Q1 after adjusting for confounders. The OBS-mortality association varied by hypertension control status, with greater risk reduction in controlled hypertension (Q4 vs. Q1, HR: 0.43; 95% CI: 0.27-0.69; P < 0.001) than in uncontrolled hypertension (Q4 vs. Q1, HR: 0.82; 95% CI: 0.66-0.87; P < 0.001). A significant interaction was observed between OBS and hypertension control status (P for interaction = 0.017 and 0.026), corroborated by sensitivity analyses (P for interaction = 0.025). Sensitivity analyses confirmed Nutrition-OBS reduced all-cause mortality by 31%, and Lifestyle-OBS decreased cardiovascular mortality by 45%. RCS analyses verified the inverse OBS-mortality relationship, with mediation analysis revealing partial mediation through low-grade systemic inflammation and multi-organ function.

Conclusions: A higher OBS is associated with lower all-cause and cardiovascular mortality under different hypertension control cascade outcomes, with a more pronounced effect in controlled hypertension. This relationship is partially mediated through systemic inflammation and multi-organ function.