A Sex-Specific Comparative Analysis of Oxidative Stress Biomarkers Predicting the Risk of Cardiovascular Events and All-Cause Mortality in the General Population: A Prospective Cohort Study

Abstract

Oxidative stress plays a pivotal role in cardiovascular (CV) disease, but current biomarkers used to predict CV events are still insufficient. In this study, we comparatively assessed the utility of redox-related biomarkers in predicting the risk of CV events and all-cause mortality in male and female subjects from the general population. Subjects (n = 5955) of the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) population-based cohort study were included. Blood homocysteine, gamma-GT, HDL cholesterol, bilirubin and protein-adjusted free thiol (R-SH, sulfhydryl groups) levels were quantified at baseline and were prospectively analyzed in association with the risk of CV events and all-cause mortality. After adjustment for potentially confounding factors, protein-adjusted R-SH and homocysteine levels were significantly associated with the risk of CV events in men (HR 0.63 [0.40–0.99], p = 0.045 and HR 1.58 [1.20–2.08], p = 0.001, respectively). Protein-adjusted R-SH and HDL cholesterol levels were significantly associated with the risk of all-cause mortality in men (HR 0.52 [0.32–0.85], p = 0.009 and HR 0.90 [0.85–0.94], p < 0.001, respectively), while the same was observed for bilirubin and homocysteine levels in women (HR 0.68 [0.48–0.98], p = 0.040 and HR 2.30 [1.14–3.76], p < 0.001, respectively). Lower levels of protein-adjusted R-SH were robustly associated with an increased risk of CV events and all-cause mortality in men. Our results highlight the value of R-SH levels in cardiovascular risk assessment and their potential significance as being amenable to therapeutic intervention, while reaffirming the importance of other oxidative stress-related biomarkers, such as homocysteine, HDL cholesterol and bilirubin.

The Impact of Physical Exercise on Oxidative and Nitrosative Stress: Balancing the Benefits and Risks

“…Diets rich in natural antioxidant sources, such as fruits, vegetables, soy, fish, and nuts, are essential for health promotion and disease prevention. The focus on natural food sources for antioxidants supports broader dietary guidelines aimed at improving the overall wellbeing of the general population [81][82][83].…”

The Impact of Physical Exercise on Oxidative and Nitrosative Stress: Balancing the Benefits and Risks

“…Understanding how demographic factors such as age, gender, health status, ethnicity, and socioeconomic background influence oxidative and nitrosative stress responses to exercise is crucial for developing personalized health and fitness programs [80][81][82][83][84]. Older adults, who naturally experience declines in antioxidant production and mitochondrial function, may benefit from moderate-intensity exercises combined with antioxidant-rich diets to counteract age-related oxidative stress [85].…”