Interacting and joint impact of oxidative balance score and insulin resistance on cardiovascular and metabolic diseases risks: a cross-sectional, population-based study

‌Oxidative stress and insulin resistance (IR) are risk factors for cardiovascular and metabolic diseases (CVMDs). However, the interaction between the oxidative balance score (OBS, marker of oxidative stress), and the triglyceride-glucose index (TyG, IR surrogate), on CVMDs risk, remains largely unexplored.

This cross-sectional, population-based study used data from the National Health and Nutrition Examination Survey (NHANES, 1999–2018), examining OBS and TyG. All exposures and outcomes were ascertained at the same time point; therefore, only associational relationships are reported. The primary outcome was the prevalence of four major CVMDs—cardiovascular disease (CVD), hypertension, type 2 diabetes mellitus (T2DM), and hyperlipidemia.

Among 17,265 participants, the prevalence rates were 8.5% for CVD, 36.9% for hypertension, 13.6% for T2DM, and 71.4% for hyperlipidemia. TyG significantly mediated the relationship between OBS and CVMD risk, with mediation proportions of 1.8% for CVD, 7.8% for hypertension, and 10.5% for T2DM. No statistically significant multiplicative or additive interactions between OBS and TyG in influencing CVMDs risk were observed. Participants with low OBS and high TyG levels had significantly increased risks for CVD, hypertension, T2DM, and hyperlipidemia, with adjusted odds ratios of 1.52 (95% confidence interval [CI]: 1.21-1.92), 1.62 (95%CI: 1.38-1.91), 2.94 (95%CI: 2.13-4.04), and 9.52 (95%CI: 7.51-12.1), respectively, compared to those with high OBS and low TyG levels. Adding OBS and TyG to traditional CVMDs risk models resulted in very small improvements in the C-statistic (ΔC <0.003 for most outcomes).

This study suggests that TyG is associated with a mediation effect between oxidative stress on CVMDs risk and underscores the co-exposure effects of OBS and TyG on CVMDs risk, highlighting the importance of a combined OBS and TyG assessment for improved CVMDs risk stratification. Because of the cross-sectional design and the mathematical overlap between TyG and the hyperlipidemia definition, causal inferences cannot be made, and the hyperlipidemia findings require independent validation.