Sex-dependent association between inflammation, neural stress responses, and impaired myocardial function

Abstract

Purpose

Evidence to date has failed to reveal unique female determinants of cardiovascular disease. However, a strong association was recently observed between increased metabolic activity in the amygdala, a neural centre involved in the processing of emotions, and impaired myocardial function in women, but not in men. Given the stronger immune responses in females, we sought to retrospectively investigate the interaction between inflammation, perceived stress, and myocardial injury.

Methods

Overall, 294 patients (mean age 66.9 ± 10.0 years, 28.6% women) underwent both, 99mTc-tetrofosmin single-photon emission computed tomography myocardial perfusion imaging and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography for the assessment of cardiac function, bone marrow metabolism (surrogate marker of inflammation), and resting amygdalar activity.

Results

A positive association was found between amygdalar metabolism and 18F-FDG bone marrow uptake in women (r = 0.238, p = 0.029), but not in men (r = 0.060, p = 0.385). Linear regression models selected both, abnormal left ventricular ejection fraction (LVEF) and abnormal myocardial perfusion, as significant indicators of an increased amygdalar activity in women (B-coefficient LVEF, − 0.096; p = 0.021; abnormal myocardial perfusion, 3.227; p = 0.043), but not in men (bone marrow p = 0.076; abnormal myocardial perfusion p = 0.420). Accordingly, an interaction term consisting of sex and LVEF/abnormal myocardial perfusion was significant (p = 0.043 and p = 0.015, respectively).

Conclusions

Upregulated amygdalar metabolism is associated with an enhanced inflammatory state in female patients with impaired cardiac function. Given that enhanced activity of the limbic system is associated with worse cardiovascular outcomes, our study suggests that a focus on inflammatory markers and indicators of distress might help to tailor cardiovascular risk assessment and therapy towards the female cardiovascular phenotype.

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Acknowledgements

We would like to thank the staff at the Department of Nuclear Medicine of the University Hospital Zurich for their contribution to this study.

Funding

CG was supported by grants from the Swiss National Science Foundation (SNSF), the Olga Mayenfisch Foundation, Switzerland, the OPO Foundation, Switzerland, the Novartis Foundation, Switzerland, the Swissheart Foundation, the Helmut Horten Foundation, Switzerland, and the EMDO Foundation, Switzerland. MF was supported by the Swiss Paraplegic Center, Nottwil, Switzerland. MM was supported by the Iten-Kohaut Foundation, Switzerland.

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Correspondence to Michael Fiechter.

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Conflict of interest

All authors have the following to disclose: The University Hospital of Zurich holds a research contract with GE Healthcare. CG has received research grants from the Novartis Foundation, Switzerland, and speaker’s fees from Sanofi Genzyme.

Ethical approval

Our study was approved by the local ethics board (BASEC No. 2017–01112) and is in line with the Declaration of Helsinki (including later amendments). The need for informed consent was waived by the local ethics board due to the retrospective design of the present study.

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Fiechter, M., Haider, A., Bengs, S. et al. Sex-dependent association between inflammation, neural stress responses, and impaired myocardial function. Eur J Nucl Med Mol Imaging 47, 2010–2015 (2020). https://doi.org/10.1007/s00259-019-04537-8

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Keywords

  • Amygdala
  • Inflammation
  • Myocardial perfusion imaging
  • Sex
  • PET