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

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This study identified causal links between circulating inflammatory proteins and heart failure types (ICM, DCM, HCM). Findings offer insights into heart failure mechanisms, diagnosis, and potential drug targets for better patient outcomes.

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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.