Systemic inflammatory regulators and heart failure: A bidirectional 2-sample Mendelian randomization study.

Area of Science:

• Cardiovascular Science
• Immunology
• Genetics

Background:

• The link between systemic inflammation and heart failure (HF) is debated, with uncertainty regarding its role in HF development.
• Understanding this relationship is crucial for identifying potential therapeutic targets for HF.

Purpose of the Study:

• To investigate the bidirectional causal relationship between systemic inflammatory regulators and heart failure (HF) using Mendelian randomization (MR).
• To identify specific inflammatory factors that causally influence HF risk or are consequences of HF.

Main Methods:

• Utilized Mendelian randomization (MR) with large-scale genome-wide association study data for HF and inflammatory regulators.
• Employed inverse variance weighting and sensitivity analyses (MR-Egger, weighted median, MR-PRESSO) to assess causality.

Main Results:

• Identified macrophage inflammatory protein-1β (MIP-1β) and Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) as causal risk factors for HF.
• Found Macrophage Migration Inhibitory Factor (MIF) to be a protective factor against HF.
• Reverse MR analyses showed no evidence of HF causing changes in systemic inflammation.

Conclusions:

• MIP-1β and RANTES are implicated as causal risk factors, while MIF is a protective factor in heart failure.
• Findings support a unidirectional causality model where inflammation influences HF, not vice versa.
• These inflammatory regulators represent potential upstream therapeutic targets for heart failure management.