The relationship between inflammatory factors and heart failure: evidence based on bidirectional Mendelian...

Area of Science:

• Cardiovascular Research
• Immunology
• Genetics

Background:

• Inflammatory factors are implicated in heart failure development and progression.
• Understanding the causal relationship between specific inflammatory cytokines and heart failure is crucial for therapeutic development.

Purpose of the Study:

• To investigate the causal associations between 91 inflammatory cytokines and heart failure using a bidirectional Mendelian randomization approach.
• To identify specific inflammatory factors that may promote or protect against heart failure.

Main Methods:

• Bidirectional Mendelian randomization analysis was performed.
• Data from large-scale genome-wide association studies for 91 inflammatory factors and the FINNGEN database for heart failure were utilized.
• Multiple sensitivity analyses, including MR-Egger, Inverse Variance Weighted, and Cochran's Q test, were conducted to ensure result robustness.

Main Results:

• Forward Mendelian randomization identified seven inflammatory factors causally related to heart failure.
• CXCL9 and Interferon-gamma (IFN-γ) were associated with increased heart failure risk, while Leukemia inhibitory factor receptor (LIFR) and Uroplakin (UPA) showed potential protective effects.
• Reverse Mendelian randomization suggested potential feedback effects of heart failure on certain inflammatory factor levels.

Conclusions:

• CXCL9, IFN-γ, LIFR, and UPA are identified as key inflammatory factors potentially involved in heart failure pathogenesis.
• These findings highlight potential novel therapeutic targets for heart failure management, warranting further investigation and validation.