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

Area of Science:

• Cardiovascular Medicine
• Immunology
• Genetics

Background:

• Heart failure, including ischemic cardiomyopathy heart failure (ICM), dilated cardiomyopathy heart failure (DCM), and hypertrophic cardiomyopathy heart failure (HCM), is a significant global health concern.
• The role of circulating inflammatory proteins in the pathogenesis of different heart failure subtypes is not fully understood.
• Identifying specific inflammatory markers could improve diagnosis, prognosis, and therapeutic strategies.

Purpose of the Study:

• To investigate the causal associations between 91 circulating inflammatory proteins and three major types of heart failure: ICM, DCM, and HCM.
• To uncover potential mechanisms underlying heart failure development and progression.
• To identify novel therapeutic targets and diagnostic biomarkers for heart failure.

Main Methods:

• Utilized Mendelian randomization (MR) analysis, a robust genetic epidemiology method, to assess causal relationships.
• Employed multiple MR methods including inverse-variance weighted, weighted median estimator (WME), weighted mode (WM), and MR-Egger regression.
• Analyzed data from 91 circulating inflammatory proteins in relation to ICM, DCM, and HCM.

Main Results:

• Identified specific inflammatory proteins with causal links to ICM, DCM, and HCM.
• Found positive causal relationships for natural killer cell receptor 2B4, CXCL-6, fibroblast growth factor 5, and interleukin-10 with ICM.
• Reported negative causal relationships for CX3CL-1, C-X-C motif chemokine 9, interleukin-10, leukemia inhibitory factor receptor, and signaling lymphocytic activation molecule with ICM; and identified other proteins associated with DCM and HCM.

Conclusions:

• This study establishes causal relationships between several circulating inflammatory proteins and different heart failure subtypes.
• The findings provide a foundation for understanding heart failure pathogenesis and developing targeted therapies.
• Identified proteins may serve as adjunctive diagnostic markers or therapeutic targets for heart failure management.