Age- and sex-dependent changes in sympathetic activity of the left ventricular apex assessed by 18F-DOPA PET imaging

PLoS One. 2018 Aug 14;13(8):e0202302. doi: 10.1371/journal.pone.0202302. eCollection 2018.

Abstract

Background: Sexual dimorphism in cardiac sympathetic outflow has recently gained attention in the context of Takotsubo cardiomyopathy. Previous studies suggest that there are sex- and age-dependent differences in peripheral autonomic control, however, data on cardiac-specific sympathetic activation in aged women and men are lacking.

Methods and results: Regional quantitative analysis of cardiac fluorine-18 (18F)- Dihydroxyphenylalanine (DOPA) uptake was retrospectively performed in 133 patients (69 females, mean age 52.4±17.7 years) referred for assessment of neuroendocrine tumours (NET) by Positron-Emission-Tomography. Cardiac 18F-DOPA uptake was significantly higher in women as compared to men (1.33±0.21 vs. 1.18±0.24, p<0.001). This sex-difference was most pronounced in the apical region of the left ventricle (LV, 1.30±0.24 in women vs. 1.13±0.25 in men, p<0.001) and in individuals >55 years of age (1.39±0.25 in women vs. 1.09±0.24 in men, p<0.001). Women showed a prominent increase in myocardial 18F-DOPA uptake with age with the strongest increase seen in the LV apical region (r = 0.34, p = 0.004). Accordingly, sex and age were selected as significant predictors of LV apical 18F-DOPA uptake in a stepwise linear regression model. No age-dependent changes of cardiac 18F-DOPA uptake were observed in men or in the right ventricular region.

Conclusion: Our study suggests that aging is related to sex-specific changes in regional cardiac sympathetic activity. Future studies will have to assess whether the increase in LV apical 18F-DOPA uptake with age in women is of pathogenic relevance for the higher susceptibility of postmenopausal women to conditions associated with increased sympathetic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / metabolism*
  • Child
  • Child, Preschool
  • Dihydroxyphenylalanine
  • Female
  • Fluorine Radioisotopes
  • Heart Ventricles / diagnostic imaging
  • Heart Ventricles / metabolism*
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • Retrospective Studies
  • Sex Characteristics*
  • Sympathetic Nervous System / diagnostic imaging
  • Sympathetic Nervous System / metabolism
  • Young Adult

Substances

  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Dihydroxyphenylalanine
  • Fluorine-18

Grants and funding

This work was supported by grants from the Swiss National Science Foundation (SNSF), the Olga Mayenfisch Foundation, Switzerland, the OPO Foundation, Switzerland, the Novartis Foundation, Switzerland, and the Swissheart Foundation. We declare that the authors received research grants from the Swiss National Science Foundation (SNSF), the Olga Mayenfisch Foundation, Switzerland, the OPO Foundation, Switzerland, the Novartis Foundation, Switzerland, the Helmut Horten Foundation, Switzerland, and the Swissheart Foundation (all to Catherine Gebhard). These funding organizations did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and provided financial support only in the form of salaries (CG, SB, AH, MM) and research materials.