Does Folic Acid Intake Play Role as a Potential Indicator of Modifiable Maternal Risk Factors in Preconception Period?: A Cross-Sectional Study.

Pulmonary embolism (PE) constitutes one of the most common manifestations of venous thromboembolism, with substantial morbidity and mortality []. Specifically, based on a large epidemiological analysis of the World Health Organization mortality database from 2001 to 2023, while global age-standardized PE-related mortality decreased from 3.49 to 2.42 deaths per 100,000 population, PE continues to represent a major cause of cardiovascular mortality and disease burden []. Additionally, despite the fact that several advances have been made in this field, resulting in prompt diagnosis, effective and safe anticoagulant treatment, and implementation of multidisciplinary care, prediction of early clinical deterioration is considered a challenge. Notably, this is of paramount importance in patients who are initially classified outside the highest-risk groups based on standard classification scores but eventually experience rapid hemodynamic compromise or even death []. Indeed, current prognostic tools, such as the established PE Severity Index (PESI), have improved our everyday clinical decision-making []. Nevertheless, these scores include, mainly, variables associated with clinical severity, right ventricular strain, cardiac injury, and metabolic stress []. Therefore, the biological processes that precede or accompany clinical deterioration are not fully captured. Thus, an important gap arises: PE is not only a syndrome characterized by mechanical obstruction of the pulmonary circulation but constitutes a thromboinflammatory syndrome in which endothelial activation, platelet recruitment, coagulation imbalance, impaired fibrinolysis, and innate immune activation interact []. Furthermore, the endothelium is not a passive bystander in this process []. Hypoxia, shear stress, inflammatory mediators, and damage-associated signals are detected and integrated by the endothelium, leading to a shift toward a proadhesive, procoagulant, and inflammatory state []. Therefore, endothelial injury may “act” as a biological amplifier of PE severity.