Chronic stress is gradually accumulated and peaks prior the occurrence of Takotsubo Syndrome: preliminary results based on hair cortisol concentration

Abstract Background Takotsubo syndrome (TTS) is frequently triggered by stressful events suggesting that increased sympathetic activity has a role in its pathophysiology. Hair cortisol concentration (HCC) is a promising biomarker of excess chronic stress by measuring cortisol secreted into hairs over several weeks. Purpose We explored whether premorbid ongoing stress over several weeks assessed by HCC at 2 weeks intervals is associated with the occurrence of TTS. Methods A case-control prospective study was performed by recruiting 18 consecutive TTS patients and 36 age- and sex-matched individuals free from cardiovascular or psychiatric disease. Hair samples were collected from participants vertex. Provided that 1 cm of hair represents cortisol levels over ~1 month period, 2.5 cm of hair samples, with many strands each, were cut in equal parts of 0.5 cm, representing cortisol levels in time intervals of 0-15, 15-30, 30-45, 45-60 and 60-75 days prior to hair collection. Results All TTS patients were women with a mean age of 71.8±11.2 years. HCC was significantly higher in TTS group versus controls starting from 45 days prior to the event (Figure 1A). Based on the linear mixed effects model, HCC was higher in the TTS group compared to controls at any time point and increased over time starting from 75 days prior to the event, while the rate of increase was significantly higher in TTS versus controls (beta of interaction = 0.48; 95%CI: 0.36 – 0.60; p < 0.001). The model explained a high percentage of the variance (conditional R2 = 0.885). The plot of the predicted HCC over time by diagnosis group is shown in Figure 1B. Conclusions Our preliminary data suggest that accumulation of chronic stressful events may cause hypothalamic-pituitary-adrenal axis dysregulation and hyperactivity leading to HCC increase, and this might be implicated in the pathophysiology of TTS.Figure 1.Plot of observed and predicted HCC