A distinct group of plasma extracellular vesicles (EVs) that co-isolate with low-density lipoprotein (LDL-EVs) contains proteins involved in coagulation and fibrinolytic pathways. This work examined whether the balance between these hemostatic and fibrinolysis-related proteins within LDL-EVs corresponds to patterns of post-acute myocardial infarction (post-AMI) left ventricular (LV) remodeling, a process that can lead to heart failure. Levels of von Willebrand factor (VWF), SerpinC1, and plasminogen were quantified in LDL-EVs obtained from plasma at baseline (≤72 h after AMI), 1 month, and 6 months in a cohort of 198 individuals. Based on the 6-month change in LV end-systolic volume (≥15 increase vs. ≥15 decrease), participants were assigned to adverse (n = 98) or reverse (n = 100) remodeling categories. A multilevel longitudinal structural equation modeling (ML-SEM) framework was applied to determine predictive value independent of baseline status. At the baseline sampling point, LDL-EV cargo levels of VWF, SerpinC1, and plasminogen were comparable between the two remodeling groups. By 1 month in the adverse-remodeling group, VWF and SerpinC1 showed declines, while plasminogen rose. Conversely, in those showing reverse remodeling, VWF and plasminogen fell, with SerpinC1 showing no major change. Ultimately, compared with the adverse group, individuals with reverse remodeling displayed higher SerpinC1 and VWF but reduced plasminogen, yielding elevated VWF: Plasminogen and SerpinC1:Plasminogen ratios at both 1 and 6 months. Importantly, the ratios VWF: Plasminogen (AUC = 0.674) and SerpinC1: Plasminogen (AUC = 0.712) offered substantially better prognostic discrimination than NT-proBNP (AUC = 0.384), troponin-I (AUC = 0.467), or troponin-T (AUC = 0.389) (p < 0.001). Shifts over time in LDL-EV-associated coagulation/fibrinolysis ratios outperform established circulating biomarkers for forecasting post-AMI reverse remodeling. These results may help point to cellular mechanisms involved in structural recovery of the LV following AMI.
