Panvascular burden in sepsis: anatomical risk saturation and physiological override
H Zhang, M Liu, Y Zhang, X Wang, M Hao, Y Li, H Jiang, J GeAbstract
Background
Prognostic significance of panvascular burden in sepsis remains undefined. We tested whether vascular risk accumulates linearly or exhibits a "saturation" pattern under extreme physiological stress.
Methods
Multicentre retrospective study using MIMIC-IV (derivation, n=7,233) and eICU-CRD (external validation, n=16,504). Septic patients were stratified into hierarchical phenotypes: G0 (No Recorded Risk), G1 (Cardiometabolic Risk), G2 (Single-bed Disease), and G3 (Polyvascular Disease). Analysis employed 1:1 Propensity Score Matching (PSM), multivariable Cox regression, and Landmark analysis. Red cell distribution width (RDW) was evaluated as a physiological stress marker.
Results
Total 23,737 patients were analysed. (1) Risk Saturation (See Figure 2): Acute mortality increased from G0 to G2 but plateaued at G2. G2 (27.4%) and G3 (26.8%) showed similar crude mortality (P=0.73). Multivariable analysis confirmed G3 conferred no incremental risk beyond G2 (Derivation adj HR 0.98 [0.84-1.14]; Validation adj HR 1.01 [0.89-1.15]). This pattern persisted in the PSM cohort (HR 0.90 [0.75-1.01]), as visualized in the overlapping survival curves (Figure 2). (2) Physiological Escalation: Conversely, RDW rose linearly across phenotypes (P trend <0.001), showing no saturation. (3) Physiological Override (See Central Illustration): In 1-year landmark analysis, anatomical complexity lost prognostic value (G3 vs G2: adj HR 1.05, P=0.65). However, high physiological stress (RDW>15.5%) remained a powerful predictor (HR 2.06 [1.78-2.39]). As depicted in the Central Illustration, patients with "Simple Anatomy + High Stress" had significantly worse outcomes than "Complex Anatomy + Low Stress" (HR 2.06 vs 1.00, P<0.001).
Conclusion
Panvascular burden in sepsis demonstrates a "risk saturation" pattern, where single-bed disease already implies maximal anatomical risk. Long-term survival is governed by "physiological override", necessitating a paradigm shift from anatomy-centric to physiology-centric risk stratification.Central IllustrationFor image description, please refer to the figure legend and surrounding text.Evidence of Risk SaturationFor image description, please refer to the figure legend and surrounding text.