The relation between stress-related neural activity assessed by brain 18F-FDG-PET/CT and cardiovascular outcomes: a systematic review and meta-analysis

Purpose

Our study aims to investigate the associations between stress-related neural activity (SNA), a quantified imaging biomarker in processing stress responses assessed by ¹⁸F-FDG-PET/CT, and cardiovascular (CV) outcomes based on available evidence.

Methods

We searched databases from inception to December 1, 2024. Studies assessing the associations between SNA, as quantified by measuring FDG uptake values in the amygdala using ¹⁸F-FDG-PET/CT, and CV outcomes were included. Risk of bias was evaluated using the Newcastle–Ottawa Scale. Random-effects model was implemented for pooled effect sizes (ESs) and heterogeneity evaluation.

Results

Ten studies with 3523 patients with ¹⁸F-FDG-PET/CT were included in our analysis (mean age: 58.5 years; 48.9% female). The ESs included in the analysis comprised hazard ratios (HR) and standardized mean differences (SMD). Among the studies reporting HR, 192 (11.5%) patients experienced composite adverse CV events during a mean follow-up period of 3.8 years. SNA significantly correlated with an increased risk of composite adverse CV events (pooled adjusted HR: 1.61, 95% confidence interval [CI]: 1.12, 2.32). Among the studies reported SMD, individuals experienced composite adverse CV events had significantly higher SNA values than those who did not (Hedges’s g = 0.55, 95% CI: 0.14, 0.96).

Conclusions

SNA, as a noninvasive quantified indicator of processing stress responses assessed by brain ¹⁸F-FDG-PET/CT, is associated with an increased risk of CV outcomes. Further research is warranted to validate these findings and to investigate the clinical utility of SNA across various demographic groups.