Sedentary Duration and Systemic Health Burden: Nonlinear Associations with Muscle, Fat, and Vascular Phenotypes in a US Population-Based Study

<b>Background:</b> Sedentary behavior (SB) is a growing public health concern associated with cardiometabolic risk; yet few studies have assessed integrated physiological responses across the muscle-fat-vascular system. <b>Methods:</b> This retrospective cross-sectional analysis used data from 13,637 participants (≥12 years) in the 2011-2018 National Health and Nutrition Examination Survey (NHANES). Sedentary duration (SD) was self-reported via a validated questionnaire. Outcomes included the sarcopenic index (SI), fat distribution index (FDI), and pulse pressure index (PPI). Associations were examined using multivariable linear regression and restricted cubic spline models, adjusting for sociodemographic and lifestyle factors. Subgroup analyses explored effect modification by body mass index (BMI), sex, race/ethnicity, education, and self-rated health. <b>Results:</b> Each additional hour/day of SD was associated with a lower SI (β = -0.004, 95% CI: -0.005 to -0.002), lower FDI (β = -0.009, 95% CI: -0.012 to -0.007), and higher PPI (β = 0.001, 95% CI: 0.000 to 0.002). The SD-SI association was nonlinear, with a threshold at 10.73 h/day: below this point, the SI declined sharply (β = -0.001, <i>p</i> < 0.001), while above it the slope plateaued or reversed. The FDI showed consistent adverse associations across the SD range, particularly in men and individuals with lower education. The PPI was significantly elevated with SD only among non-Hispanic Black participants. <b>Conclusions:</b> SD is differentially associated with muscle mass, fat distribution, and vascular function, with overlapping inflection points indicating a coordinated multisystem response to sedentary stress. These findings support targeting <10.7 h/day sedentary time as a potential intervention threshold.