Abstract
Previous studies have shown that serum albumin levels are associated with a greater risk of metabolic syndrome (MetS). However, it is unclear whether this association is causal or only influenced by confounding factors, so further investigation is needed to determine the causal relationships. Researchers selected participants with serum albumin, metabolic syndrome, and related covariates from the National Health and Nutrition Examination Survey (NHANES) database for a total of 14,036 individuals, including 5483 individuals with MetS and 8553 individuals without MetS. The association of serum albumin levels with metabolic syndrome and its components was estimated using weighted multivariable logistic regression, with its nonlinearity being examined by restricted cubic spline (RCS) regression. Bidirectional two-sample Mendelian randomization (MR) analysis was performed using Genome-Wide Association Study (GWAS) data on serum albumin and MetS to assess the causal relationship between serum albumin levels and MetS and its components. The primary MR analyses were performed via an inverse variance weighting (IVW) approach. In addition, several sensitivity analyses were performed to assess the robustness of the results. The STROBE-MR checklist for the reporting of MR studies was used in this study. After confounder adjustment, when the serum albumin levels were analyzed as a continuous variable, the multivariable logistic analysis revealed a significant association between it and metabolic syndrome (OR: 1.032, 95% CI: 1.012-1.052). When the serum albumin levels were used as categorical variables, the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for metabolic syndrome across higher serum albumin levels quartiles were 0.981 (0.842-1.143), 1.290 (1.115-1.492), and 1.244 (1.064-1.454) compared to the lowest quartile, respectively. In the forward MR study, the IVW method revealed that genetic predicted increased levels of serum albumin were positively correlated with metabolic syndrome (OR: 1.149, 95% CI: 1.016-1.299) and its components, including hypertension (OR: 1.130, 95% CI: 1.013-1.260) and triglycerides (OR: 1.343, 95% CI: 1.209-1.492). In the reverse MR study, the IVW method showed no significant causal relationship between MetS, hypertension, fasting blood glucose and HDL-C with serum albumin levels. The results from the NHANES and MR analysis have revealed a causal relationship between serum albumin levels and both metabolic syndrome and hypertension, indicating that elevated levels of serum albumin are a risk factor for these conditions. Our results provide new biomarkers for preventive and therapeutic strategies for metabolic syndrome.