Serum albumin levels and pulmonary embolism risk: insights from observational and mendelian randomization studies

Abstract BACKGROUND: Previous observational studies have linked serum albumin (ALB) to prognosis in patients with pulmonary embolism (PE). Nevertheless, the nature of the association between serum albumin and PE risk remains unclear, and the potential causality requires to be investigated. Our study aimed to integrate an observational study and a two-sample Mendelian randomization (MR) analysis to comprehensively assess the relationship between serum albumin and PE risk. METHODS: A total of 13,326 participants, consisting of 749 PE patients and 12,577 non-PE controls, were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database for an observational study. The effects of serum albumin on PE risk were assessed using propensity score matching (PSM) and restricted cubic spline (RCS) model analysis, adjusting for multiple covariates. Subsequently, a two-sample MR analysis was performed using summary statistics from genome-wide association studies (GWAS) to assess the causality between serum albumin and PE risk. Sensitivity analyses were carried out to confirm the robustness of MR results. RESULTS: The results of PSM indicated that the serum albumin levels were lower in PE patients (3.97 g/dL) than in non-PE controls (4.09 g/dL). The RCS model demonstrated a linear negative correlation between serum albumin and PE risk (P for nonlinear > 0.05). MR analysis confirmed a causality between serum albumin (OR = 0.744, 95% CI: 0.642~0.861, P < 0.001) and PE risk. CONCLUSION: Our study provided evidence that low serum albumin appeared to be associated with an increased risk of PE, and this association was possibly causal.