Lifestyle, metabolic, and gut microbial determinants of hypertension onset according to metabolic dysfunction status: insights from the population-based FoCus study

Background : Hypertension is closely associated with metabolic dysfunction; however, whether the determinants of hypertension onset differ according to metabolic status remains unknown. We aimed to investigate the lifestyle, metabolic, and gut microbial signatures associated with hypertension prevalence and onset according to metabolic phenotypes. Methods : We used comprehensive data from the German population-based Food Chain Plus (FoCus) cohort. Participants were classified according to their metabolic dysfunction status. Cox proportional hazards and restricted cubic spline (RCS) regression analyses were performed to evaluate the associations between metabolic biomarkers, lifestyle factors, gut microbiota diversity, and age-at-hypertension-onset. Results : Among individuals with metabolic dysfunction, elevated WHtR (HR = 1.876,95%CI, 1.411–2.495; P = 0.0003), TyG index (HR = 1.313, 95% CI: 1.024-1.684; P = 0.0317), and HOMA-β (HR = 1.319, 95% CI: 0.974-1.786; P = 0.0389) were significantly associated with an earlier onset of hypertension. Conversely, higher relative handgrip strength of the right hand (HR = 1.025, 95% CI: 1.006-1.044; P = 0.0105), greater microbial diversitymeasured using the Chao1 index(HR = 0.672, 95% CI: 0.495-0.913; P = 0.0076), and observed index (HR = 0.667, 95% CI: 0.492-0.906; P = 0.008) were associated with delayed hypertension onset. Among individuals without metabolic dysfunction, only sports and television watching were associated with the timing of hypertension onset, whereas biomedical and gut microbial markers were not significantly associated. Conclusions: Hypertension exhibits substantial metabolic heterogeneity. Metabolic dysfunction is accompanied by distinct metabolic and gut microbial signatures associated with earlier hypertension onset, whereas lifestyle factors appear to play a greater role in individuals without metabolic dysfunction. These findings support the importance of metabolic stratification for the precision prevention and targeted management of hypertension.