REN and heart failure: Symptom network analysis is also vulnerable to interference from unmeasured confounders (e.g., subclinical inflammation, autonomic dysfunction): for example, fluid retention dominated by renin-angiotensin-aldosterone system activation in the heart failure with reduced ejection fraction (HFrEF) group may strengthen the “edema-weight gain” association, while chronic microinflammation in the HFpEF group may simultaneously exacerbate fatigue, anxiety, and sleep disorders, leading to spurious correlations.[33]