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Pathophysiological Sex Differences in Heart Failure Progression After Acute Coronary Syndrome: Insights From the

Amir Razaghizad1, Haya Aziz2, Guang K Zhang3

  • 1Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; Division of Cardiology, McGill University Health Centre, McGill University, Montreal, Quebec, Canada; DREAM-CV Lab, McGill University Health Centre, McGill University, Montreal, Quebec, Canada.

Journal of Cardiac Failure
|November 8, 2023
PubMed

Insights

Sex differences in heart failure (HF) risk exist in type 2 diabetes. Interleukin-6 is key in HF development, with females showing more inflammatory markers linked to HF hospitalization.

Area of Science:

  • Cardiovascular Medicine
  • Endocrinology
  • Immunology

Background:

  • Type 2 diabetes increases heart failure (HF) risk.
  • Females with type 2 diabetes face a higher risk of HF development and progression compared to males.
  • Understanding sex-specific differences in HF pathogenesis is crucial for targeted therapies.

Purpose of the Study:

  • To investigate sex differences in heart failure (HF) development and progression.
  • To compare baseline circulating proteins in males and females with type 2 diabetes and acute coronary syndrome.
  • To identify biomarkers associated with HF hospitalization risk in a sex-specific manner.

Main Methods:

  • Analysis of data from the placebo-controlled Examination of Cardiovascular Outcomes with Alogliptin vs Standard of Care (EXAMINE) trial.
  • Comparison of baseline circulating proteins using the Olink Cardiovascular II panel in males and females.
  • Network and pathway over-representation analyses to interpret pathophysiological sex-differences.

Main Results:

  • 43 biomarkers were differentially expressed in HF hospitalization, with 18 being sex-specific.
  • Interleukin-6 was identified as a central node in HF pathogenesis for both sexes.
  • Females showed higher up-regulation of inflammatory biomarkers related to endothelial dysfunction and cardiac fibrosis.

Conclusions:

  • Interleukin-6 plays a central role in HF pathogenesis in both males and females with type 2 diabetes and acute coronary syndrome.
  • Females exhibit distinct patterns of circulating proteins, particularly related to immunological pathways, highlighting sex-specific HF development.
  • Specific biomarkers (e.g., pentraxin-related protein 3) were independently associated with increased HF hospitalization risk in females.
Abstract

Keywords:
Proteomicsdiabetesepidemiologyheart failuresex differences

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