The causal relationship between circulating inflammatory proteins and heart failure: A two-sample Mendelian randomization study

This study aims to explore the causal associations of 91 circulating inflammatory proteins with ischemic cardiomyopathy heart failure (ICM), dilated cardiomyopathy heart failure (DCM), and hypertrophic cardiomyopathy heart failure (HCM) to provide new ideas for the study of relevant heart failure mechanisms, adjunctive diagnosis and differentiation, and the clinical application of relevant drug targets. An analysis of the causal relationship between circulating inflammatory proteins and heart failure was conducted via inverse-variance weighted, weighted median estimator (WME), weighted mode (WM), and Mendelian randomization-Egger regression with Mendelian randomization. A Mendelian randomization analysis of 91 circulating inflammatory proteins revealed that natural killer cell receptor 2B4 levels, CXCL-6, fibroblast growth factor 5 levels, and interleukin-10 levels had positive causal relationships with ICM, whereas CX3CL-1, C-X-C motif chemokine 9 levels, interleukin-10 levels, leukemia inhibitory factor receptor levels, and signaling lymphocytic activation molecule levels had negative causal relationships; C-C motif chemokine 20 levels, C-X-C motif chemokine 5 levels, C-X-C motif chemokine 9 levels, fibroblast growth factor 5 levels, and oncostatin-M levels were positively correlated with DCM, whereas eukaryotic translation initiation factor 4E-binding protein 1 levels and Fms-related tyrosine kinase 3 ligand levels were negatively associated with DCM; and the CD40L receptor, Fms-related tyrosine kinase 3 ligand levels, hepatocyte growth factor levels, and sulfotransferase 1A1 levels were negatively associated with HCM. In this study, 9 of the 91 circulating inflammatory proteins were causally related to the ICM (4 positive, 5 negative), 7 were causally related to the DCM (5 positive, 2 negative), and 4 were causally related to the HCM (all negative). This study provides a theoretical foundation for the study of the relevant mechanisms of heart failure, clinical diagnosis, and treatment, as well as potential drug candidates closely related to heart failure.