Associations of metabolic indicators and inflammation-related indices with adverse cardiovascular events in US adults: NHANES 1999–2018

Processes in cardiovascular disease (CVD) are associated with metabolic perturbations and inflammation. The mediating role of inflammation in connecting metabolic factors to adverse cardiovascular outcomes and the joint effects of both factors on CVD and mortality are poorly understood. A total of 18,741 individuals from the National Health and Nutrition Examination Survey 1999–2018 were included in this study. Multivariate survey-weighted logistic regression (for CVD prevalence) and Cox proportional hazards models (for all-cause and CVD mortality) were used to investigate associations among metabolic factors, inflammation-related variables, and adverse cardiovascular outcomes. Mediation analyses were conducted to explore how inflammation may contribute to the relationship between metabolic factors and adverse cardiovascular outcomes. Joint factor models for both metabolic and inflammatory risk factors were developed for comprehensive evaluation. With each unit rise in the triglyceride–glucose (TyG) index and Dietary Inflammatory Index (DII), the prevalence of CVD and risks of all-cause and CVD mortality escalated by 22% vs. 6% (odds ratio [OR] = 1.22, 95% confidence interval [CI; 1.06, 1.41] vs. 1.06 [1.02, 1.11]), 20% vs. 12% (hazard ratio [HR] = 1.20, 95% CI [1.09, 1.32] vs. 1.12 [1.09, 1.15], and 29% vs. 12% (HR = 1.29, 95% CI [1.01, 1.64] vs. 1.12 [1.05, 1.18]), respectively. Mediation analysis indicated that the DII accounted for 3.58% (95% CI 3.50%, 3.66%) to 17.05% (95% CI 7.77%, 85.09%) of the association of the TyG and atherogenic index of plasma with the prevalence of CVD and risks of all-cause and CVD mortality. Joint effect analysis according to tertiles (T) revealed that compared with the TyG-T1 + DII-T1 group, the TyG-T3 + DII-T3 group had greater CVD prevalence (OR = 1.45, 95% CI [1.02, 2.06]) and elevated risks of all-cause and CVD mortality (HR = 1.80 95% CI [1.47, 2.21]); 1.75 95% CI [1.14, 2.67]). The study findings revealed that metabolic disturbances and the inflammatory burden have important roles in increasing the prevalence of CVD and risks of all-cause and CVD mortality. Low-cost laboratory and dietary indicators can complement existing assessment, enabling scalable early risk stratification and prioritized primary care intervention to reduce premature CVD deaths across secondary and tertiary prevention.