Abstract
<title>Abstract</title> <p> Background Current tools for risk stratification for acute pulmonary embolism (PE) have limited accuracy, and lipid parameters have been associated with thrombotic risk and may offer prognostic information in PE. This study aimed to identify prognostic lipid markers for acute PE to optimize risk assessment and improve clinical management. Methods Patients with acute PE were enrolled from two centres, comprising a discovery cohort of 1231 patients and a validation cohort of 215 patients. Lipid profiles were assessed in all participants. The primary endpoint was 30-day all-cause mortality. The prognostic significance of lipid parameters was assessed using Kaplan‒Meier survival analysis, Cox regression models, the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results After full adjustment, only high HDL-C levels were independently associated with a low 30-day mortality risk (adjusted hazard ratio [HR] 0.33 per 1 mmol/L, 95% CI 0.13–0.85; <italic>P</italic> = 0.021). An HDL-C cut-off of 0.94 mmol/L predicted mortality, with an AUC of 0.707. Adding HDL-C to the 2019 European Society of Cardiology (ESC) model significantly improved its predictive performance. The AUC increased from 0.750 to 0.789 in the discovery cohort and from 0.743 to 0.774 in the validation cohort (both <italic>P</italic> < 0.05). Reclassification also improved significantly (NRI and IDI, both <italic>P</italic> < 0.05), and the prognostic value of HDL-C was consistent across ESC risk strata. Conclusion Low HDL-C is independently associated with increased short-term mortality in acute PE and offers incremental prognostic value beyond 2019 ESC stratification </p>