Abstract

Introduction. Takotsubo Syndrome (TS) has been associated with acute stress exposure and excessive activation of the adrenergic nervous system. Less is known about the role of chronic stress and of the hypothalamic-pituitary-adrenal (HPA) axis in the pathophysiology of TS. Hair cortisol concentration (HCC) is a novel biomarker of chronic stress and HPA axis activation. Plasma cortisol is incorporated in growing hair (average growth rate = 1 cm/month), reflecting HPA axis activity over the preceding months. In this study we measured HCC in TS patients and explored associations between HCC, trigger status, and psychological characteristics at enrollment. Methods. HCC was measured in a group of patients admitted with a new TS diagnosis based on Mayo Clinic criteria (n=18). Demographics, perceived stress, depression, anxiety, PTSD symptoms, coping skills, and resilience (self-report questionnaires); trigger history (standardized in-person interview); and HCC were collected at the baseline visit. Hair strands were cut near the scalp from a posterior vertex position. HCC was measured in the first 3 cm of hair, which reflects plasma cortisol levels during the previous 3 months. Samples were washed, ground, extracted in HPLC-grade methanol, and quantified (pg/mg) using a high-sensitivity enzyme immunoassay (EIA) kit. Descriptive statistics were used to characterize the sample, and Spearman rho to examine associations. A p value (2-sided) < .05 was considered significant. Results. Participants were 65.6 (SD 9.4) years old, 100% female, 100% white, 10% Hispanic. 52% married/living as married. Median HCC was 6.35 pg/mg (IQR 3.6, 15.2). HCC was significantly higher in patients reporting no triggers vs. those reporting a trigger prior to the TS episode (14.9 vs. 6.8 pg/ml, p=0.03). No associations were found between psychological measures and HCC, except for a non-significant inverse association between HCC and PTSD symptoms (rho=-0.35; p=0.14). Conclusions. This first exploration of HCC levels in patients with a recent TS episode suggests that chronic HPA axis activation likely does not play a role in the pathophysiology of TS. Findings need to be confirmed in a controlled study with a larger and more diverse sample.

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