Cumulative behavioral and metabolic determinants of health are associated with higher inflammation-related indices: insights from a cross-sectional study (NHANES 2005-2018)

Anzhi Wang¹Youping Zeng¹Xiaoyan Gao¹Shenshen Du¹Ping Wang²Yun Pan^1*

• ¹First Affiliated Hospital of Jinan University, Guangzhou, China
• ²Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China

Objective: This study innovatively investigates the cumulative associations between behavioral determinants of health (BDoH), metabolic determinants of health (MDoH), and systemic inflammation biomarkers in U.S. adults, using a novel cross-sectional framework to quantify their synergistic effects.: Utilizing cross-sectional data from 18,500 participants in the National Health and Nutrition Examination Survey (NHANES 2005-2018 cycle), we developed a composite exposure model integrating BDoH (smoking status, physical activity, dietary quality) and MDoH (obesity metrics, hypertension, diabetes) through standardized questionnaires and clinical measurements. Systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI) were calculated from peripheral blood cell counts. Multivariable-adjusted logistic regression models examined doseresponse relationships, with trend analysis explicitly testing cumulative BDoH-MDoH interactions. Results: The cohort (mean age 44.3±0.3 years; 52.4% male) demonstrated significant positive associations between adverse health determinants and inflammatory indices. Current tobacco use (OR=1.32, 95%CI=1.18-1.47), suboptimal diet (HEI<52: OR=1.24, 95%CI=1.11-1.38), obesity (BMI≥30 kg/m²: OR=1.41, 95%CI=1.27-1.56), and central adipometry (OR=1.39, 95%CI=1.25-1.54) showed strongest correlations with elevated SII/SIRI. Metabolic disorders exhibited distinct patterns: hypertension and diabetes associated specifically with SIRI elevation (OR=1.19, 95%CI=1.06-1.33 and OR=1.17, 95%CI=1.03-1.32, respectively), while physical inactivity (<600 MET-min/week) uniquely correlated with SII increase (OR=1.26, 95%CI=1.13-1.40). Notably, our cumulative model revealed synergistic effects: exposure to ≥3 adverse behavioral determinants amplified inflammation risks (SII: OR=1.57, 95%CI=1.42-1.73; SIRI: OR=1.49, 95%CI=1.35-1.64), with significant dosedependent trends (P-trend<0.001). Co-occurring metabolic abnormalities demonstrated additive inflammatory effects (P-trend<0.001), exceeding individual risk factor impacts. Conclusion: This cross-sectional study provides the first evidence that integrated BDoH-MDoH cumulative exposure models uncover distinct and synergistic inflammatory pathways. Both individual and combined behavioralmetabolic risk factors significantly associate with systemic inflammation biomarker elevation, highlighting the necessity of dual-target intervention strategies.