Cardiometabolic multimorbidity and short-term outcomes in pulmonary embolism: Findings from the CURES Registry-2

Background: The impact of cardiometabolic multimorbidity (CMM), defined as the coexistence of multiple cardiometabolic diseases (CMD), on acute pulmonary embolism (PE) outcomes remains understudied. We investigated the burden of CMM and its association with short-term outcomes, treatment patterns, and potential mediators in PE. Methods: We analyzed 7284 patients with acute PE from a nationwide multicenter prospective registry. CMM was defined as the presence of ≥2 CMDs (hypertension, diabetes, dyslipidemia, pre-existing cardiovascular disease, or stroke). The primary objective was to evaluate the association between CMM and 30-day all-cause death and bleeding events. Cox regression models were used to estimate hazard ratios (HR). Sensitivity and subgroup analyses confirmed the robustness of findings, while causal mediation analysis explored underlying pathways. Results: Overall, 54.2% of patients had ≥1 CMD, and 24.8% had CMM. After multivariable adjustment, CMM was independently associated with increased risks of 30-day all-cause death (HR = 1.28, 95% CI 1.02-1.65) and bleeding (HR = 1.45, 95% CI 1.04-2.01), with mortality rising stepwise with increasing CMD burden. In intermediate-high risk PE, the presence of CMM was linked to lower use of reperfusion therapy. Mediation analysis identified body mass index, blood glucose, and renal function markers as partial drivers of these associations. Conclusion: CMM is prevalent in PE and not only independently increases the risk of 30-day all-cause death and bleeding but also may influence reperfusion treatment choices. Future studies should test adding CMM to risk assessment to improve stratification and decision-making.