Downloaded from http://heart.bmj.com/ on March 15, 2015 - Published by group.bmj.com
Heart failure and cardiomyopathies
ORIGINAL ARTICLE
Cortisol awakening and stress response, personality and psychiatric profiles in patients with takotsubo cardiomyopathy Sabrina Kastaun,1,2 Niko P Schwarz,1 Martin Juenemann,1,3 Mesut Yeniguen,1,3 Holger M Nef,4 Helge Moellmann,5 Christian W Hamm,4,5 Gebhard Sammer,6 Juergen Hennig,7 Georg Bachmann,1,8 Tibo Gerriets1,3 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ heartjnl-2014-305745). For numbered affiliations see end of article. Correspondence to Professor Tibo Gerriets, Department of Neurology, Heart & Brain Research Group, University Hospital Giessen and Marburg, Klinikstraße 33, Giessen 35392, Germany; [email protected]. uni-giessen.de Received 21 February 2014 Revised 4 June 2014 Accepted 8 June 2014 Published Online First 1 July 2014
ABSTRACT Objective Alterations in cortisol awakening and stress responses (CAR, CSR) are sensitive markers for the basal activity and responsiveness of the hypothalamus– pituitary–adrenal axis (HPAA) in psychopathological conditions. We investigated whether patients with takotsubo cardiomyopathy (TTC) differ in these markers when compared with non-ST-segment elevation myocardial infarction (NSTEMI) patients and healthy controls. Methods 19 female TTC patients were compared with 20 female NSTEMI patients and with 20 healthy women, matched by age and index event date. Salivary sampling indicated cortisol release, questionnaires assessed personality, life events, chronic stress and psychiatric symptoms. Results The groups did not differ relevantly in their basal HPAA activity, psychiatric or personality profiles. Despite increased heart rates in response to stress (median difference (MDdiff )=3.5, p=0.002) and higher nervousness scores (MDdiff=−3.0, p=0.024), TTC patients revealed a blunted CSR with a medium effect compared to the controls (MDdiff=−3.2 nmol/L, p=0.022, r=0.36); even when controlled for prestress cortisol differences ( p=0.044, r=0.33). In comparison with NSTEMI patients, no significant differences in CSR (MDdiff=−1.9 nmol/L, p=0.127, r=0.25) or nervousness (MDdiff=2.0, p=0.107) can be observed. Stressful life events, for example, traumatic experiences, occurred more often in TTC (42%) than in NSTEMI patients and controls (both 10%, p=0.031). Conclusions In this small exploratory trial, a trend for a blunted CSR and high incidences of stressful life events were observed in TTC patients. If these results can be confirmed in larger studies, chronic stress and the inhibitory influence of cortisol on catecholamine release might be significant for the pathogenesis of TTC.
INTRODUCTION
To cite: Kastaun S, Schwarz NP, Juenemann M, et al. Heart 2014;100:1786–1792. 1786
The aetiology of takotsubo cardiomyopathy (TTC) is still poorly understood. The most established theory of catecholamine-mediated myocardial stunning being provoked by emotional or physiological stress is supported by supraphysiological levels of plasma catecholamines in TTC patients.1 2 However, no stressful trigger is observed in approximately one-third of the patients.3 TTC predominantly occurs in postmenopausal women, and
recent studies suggest a predisposing influence of psychiatric disorders, psychosocial stress4 and type D personality5 in its pathogenesis. Excessive or inadequate basal activity or responsiveness of the hypothalamus–pituitary–adrenal axis (HPAA) are sensitive indicators for health and psychological conditions. Free salivary cortisol is released in response to a stressor, with its peak after ∼20 min.6 It also follows a circadian rhythm, as it increases after awakening and continuously declines throughout the day.7 Whereas cortisol stress response (CSR) indicates HPAA reactivity, cortisol awakening response (CAR) provides insight into the basal physiological functioning of the HPAA. Altered CAR profiles are associated with depression8 9 and hyporesponsiveness of the HPAA has often been reported in stress-related disorders.7 10 11 The present hypotheses-generating study investigates basal HPAA activity and HPAA responsiveness in TTC patients for the first time. The results were contrasted to those of patients with myocardial infarction and healthy controls. Moreover, we aimed to identify predisposing psychiatric and personality pattern, as well as stressful life events, that may be linked to altered cortisol profiles in patients with TTC.
METHODS Study population Data were collected from 19 female TTC patients diagnosed at Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany. Inclusion criteria were in line with the Mayo Clinic criteria.3 Twenty women with a history of non-ST-segment elevation myocardial infarction (NSTEMI) and 20 cardiac-healthy female volunteers (eg, recruited via announcements from community facilities) served as control groups. All gave written, informed consent. The groups were matched by age (mean age 60.5±9.2), and the TTC and NSTEMI patients were additionally matched by their index event date in relation to study inclusion (mean months 18.4±8.5). We recorded the most prominent pharmaceuticals (if used by more than two patients) that are known to influence the physiological stress response.12 In advance, one TTC and two NSTEMI patients were excluded due to oestrogen therapy, and three TTC and seven NSTEMI patients refused to participate
Kastaun S, et al. Heart 2014;100:1786–1792. doi:10.1136/heartjnl-2014-305745
Downloaded from http://heart.bmj.com/ on March 15, 2015 - Published by group.bmj.com
Heart failure and cardiomyopathies in the study. None of our participants took oral contraceptives or corticoids. The ethics committee of the Justus-LiebigUniversity Giessen approved the study.
Measurements Stress hormones Saliva cortisol is a useful, non-invasive biomarker which reflects the HPAA activity and facilitates multi-sampling. Its concentrations are closely correlated to serum cortisol, when controlled for specific variables such as sex steroids.13 Catecholamines are known to reflect the sympathetic activity and are elevated by psychological stressors. However, its concentrations in saliva seem to be a poor index of acute changes in sympathetic activity,14 and venipuncture itself can lead to activation of stress systems. Thus, we refrain from catecholamine measurements. Salivette sampling devices (Sarstedt, Rommelsdorf, Germany) were used for saliva collection. Samples were centrifuged at 3500 rpm for 5 min and frozen at −20°C until assayed. An ELISA determined free cortisol concentrations (ELISA, IBL International GmbH, Hamburg, Germany) according to standard procedures. The intraassay and interassay variability were
Heart failure and cardiomyopathies
ORIGINAL ARTICLE
Cortisol awakening and stress response, personality and psychiatric profiles in patients with takotsubo cardiomyopathy Sabrina Kastaun,1,2 Niko P Schwarz,1 Martin Juenemann,1,3 Mesut Yeniguen,1,3 Holger M Nef,4 Helge Moellmann,5 Christian W Hamm,4,5 Gebhard Sammer,6 Juergen Hennig,7 Georg Bachmann,1,8 Tibo Gerriets1,3 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ heartjnl-2014-305745). For numbered affiliations see end of article. Correspondence to Professor Tibo Gerriets, Department of Neurology, Heart & Brain Research Group, University Hospital Giessen and Marburg, Klinikstraße 33, Giessen 35392, Germany; [email protected]. uni-giessen.de Received 21 February 2014 Revised 4 June 2014 Accepted 8 June 2014 Published Online First 1 July 2014
ABSTRACT Objective Alterations in cortisol awakening and stress responses (CAR, CSR) are sensitive markers for the basal activity and responsiveness of the hypothalamus– pituitary–adrenal axis (HPAA) in psychopathological conditions. We investigated whether patients with takotsubo cardiomyopathy (TTC) differ in these markers when compared with non-ST-segment elevation myocardial infarction (NSTEMI) patients and healthy controls. Methods 19 female TTC patients were compared with 20 female NSTEMI patients and with 20 healthy women, matched by age and index event date. Salivary sampling indicated cortisol release, questionnaires assessed personality, life events, chronic stress and psychiatric symptoms. Results The groups did not differ relevantly in their basal HPAA activity, psychiatric or personality profiles. Despite increased heart rates in response to stress (median difference (MDdiff )=3.5, p=0.002) and higher nervousness scores (MDdiff=−3.0, p=0.024), TTC patients revealed a blunted CSR with a medium effect compared to the controls (MDdiff=−3.2 nmol/L, p=0.022, r=0.36); even when controlled for prestress cortisol differences ( p=0.044, r=0.33). In comparison with NSTEMI patients, no significant differences in CSR (MDdiff=−1.9 nmol/L, p=0.127, r=0.25) or nervousness (MDdiff=2.0, p=0.107) can be observed. Stressful life events, for example, traumatic experiences, occurred more often in TTC (42%) than in NSTEMI patients and controls (both 10%, p=0.031). Conclusions In this small exploratory trial, a trend for a blunted CSR and high incidences of stressful life events were observed in TTC patients. If these results can be confirmed in larger studies, chronic stress and the inhibitory influence of cortisol on catecholamine release might be significant for the pathogenesis of TTC.
INTRODUCTION
To cite: Kastaun S, Schwarz NP, Juenemann M, et al. Heart 2014;100:1786–1792. 1786
The aetiology of takotsubo cardiomyopathy (TTC) is still poorly understood. The most established theory of catecholamine-mediated myocardial stunning being provoked by emotional or physiological stress is supported by supraphysiological levels of plasma catecholamines in TTC patients.1 2 However, no stressful trigger is observed in approximately one-third of the patients.3 TTC predominantly occurs in postmenopausal women, and
recent studies suggest a predisposing influence of psychiatric disorders, psychosocial stress4 and type D personality5 in its pathogenesis. Excessive or inadequate basal activity or responsiveness of the hypothalamus–pituitary–adrenal axis (HPAA) are sensitive indicators for health and psychological conditions. Free salivary cortisol is released in response to a stressor, with its peak after ∼20 min.6 It also follows a circadian rhythm, as it increases after awakening and continuously declines throughout the day.7 Whereas cortisol stress response (CSR) indicates HPAA reactivity, cortisol awakening response (CAR) provides insight into the basal physiological functioning of the HPAA. Altered CAR profiles are associated with depression8 9 and hyporesponsiveness of the HPAA has often been reported in stress-related disorders.7 10 11 The present hypotheses-generating study investigates basal HPAA activity and HPAA responsiveness in TTC patients for the first time. The results were contrasted to those of patients with myocardial infarction and healthy controls. Moreover, we aimed to identify predisposing psychiatric and personality pattern, as well as stressful life events, that may be linked to altered cortisol profiles in patients with TTC.
METHODS Study population Data were collected from 19 female TTC patients diagnosed at Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany. Inclusion criteria were in line with the Mayo Clinic criteria.3 Twenty women with a history of non-ST-segment elevation myocardial infarction (NSTEMI) and 20 cardiac-healthy female volunteers (eg, recruited via announcements from community facilities) served as control groups. All gave written, informed consent. The groups were matched by age (mean age 60.5±9.2), and the TTC and NSTEMI patients were additionally matched by their index event date in relation to study inclusion (mean months 18.4±8.5). We recorded the most prominent pharmaceuticals (if used by more than two patients) that are known to influence the physiological stress response.12 In advance, one TTC and two NSTEMI patients were excluded due to oestrogen therapy, and three TTC and seven NSTEMI patients refused to participate
Kastaun S, et al. Heart 2014;100:1786–1792. doi:10.1136/heartjnl-2014-305745
Downloaded from http://heart.bmj.com/ on March 15, 2015 - Published by group.bmj.com
Heart failure and cardiomyopathies in the study. None of our participants took oral contraceptives or corticoids. The ethics committee of the Justus-LiebigUniversity Giessen approved the study.
Measurements Stress hormones Saliva cortisol is a useful, non-invasive biomarker which reflects the HPAA activity and facilitates multi-sampling. Its concentrations are closely correlated to serum cortisol, when controlled for specific variables such as sex steroids.13 Catecholamines are known to reflect the sympathetic activity and are elevated by psychological stressors. However, its concentrations in saliva seem to be a poor index of acute changes in sympathetic activity,14 and venipuncture itself can lead to activation of stress systems. Thus, we refrain from catecholamine measurements. Salivette sampling devices (Sarstedt, Rommelsdorf, Germany) were used for saliva collection. Samples were centrifuged at 3500 rpm for 5 min and frozen at −20°C until assayed. An ELISA determined free cortisol concentrations (ELISA, IBL International GmbH, Hamburg, Germany) according to standard procedures. The intraassay and interassay variability were
