Temporal Relationship Between Visceral Fat and Inflammation, and Their Joint Effect on Cardiometabolic Diseases: Evidence from the China Health and Retirement Longitudinal Study (CHARLS)

Background: Both visceral fat accumulation and inflammation are commonly observed in cardiometabolic diseases (CMD). We aimed to evaluate their joint effects on CMD risk, and assessed their temporal relationship and biological interactions. Methods: The study comprised 9559 individuals from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative cohort initiated in 2011 and completed follow-up through 2020. Visceral fat was measured by the Chinese visceral adiposity index (CVAI), and inflammation was indicated by high-sensitivity C-reactive protein (hs-CRP). Multivariate regression analyses were applied to evaluate the joint effects of CVAI and hs-CRP on CMD, including hypertension, diabetes, heart diseases, and stroke. A cross-lagged panel model was used to examine the temporal relationship. Multiplicative and additive interactions were also assessed. Results: The mean age of the study population was 59.3 ± 9.6 years, and 5164 (54.0%) were women. Both cross-sectional and longitudinal analyses yielded consistent results that visceral fat and inflammation were individually and jointly associated with CMD. When evaluating the effect of co-exposure, the highest CMD risks were observed for individuals with high CVAI and hs-CRP levels. Compared with people with low CVAI (< 93.32 [median]) and hs-CRP (< 1 mg/L), those concurrently with high CVAI (≥ 93.32) and hs-CRP (≥ 1 mg/L) had double the increased risk of diabetes and stroke, and 40% increased risk of hypertension and heart diseases. A unidirectional temporal relationship from baseline CVAI to follow-up hs-CRP was observed, with a standardized correlation coefficient of 0.130 ( P < 0.001). There was significantly biological interaction between CVAI and hs-CRP, and the attributable proportion due to interaction was 19% for hypertension and 14% for diabetes. Conclusion: The concurrent visceral fat accumulation and elevated inflammation synergistically lead to highest risks of CMD. The combined assessment of both factors may improve risk stratification and primary prevention of cardiometabolic diseases. Keywords: visceral fat, inflammation, cardiometabolic diseases, additive interaction, temporal relationship