Original articleCortisol awakening response is elevated in acute coronary syndrome patients with type-D personality
Introduction
Negative affective states are robust predictors of susceptibility to and morbidity from coronary heart disease (CHD), even after controlling for traditional risk factors [1], [2]. Type-D personality and depression both predict poor prognosis in individuals following acute coronary syndrome (ACS). The pathways underpinning these relationships are not yet fully understood. This article investigated the relationship between psychological status and hypothalamic–pituitary–adrenocortical (HPA) axis function by assessing salivary cortisol repeatedly through the evening, early morning, and the remainder of the day in patients hospitalized with ACS.
Depressive symptoms and clinical depression in the days following the occurrence of ACS have been associated with increased mortality, revascularization, and impaired quality of life in a number of studies, independently of clinical risk factors [3], [4], [5]. Type-D personality [6] is a relatively recent psychological construct focusing on traits of negative affectivity and lack of emotional expression in social situations. It differs from acute symptoms of affective distress in being regarded as relatively stable over time and has been shown to predict adverse clinical outcomes in patients following ACS, individuals who have undergone revascularization, and patients with heart failure [6], [7], [8], [9]. Both the negative affectivity and social inhibition components of type-D appear to be important, acting synergistically to predict morbidity.
Several pathways that potentially relate negative affective states with CHD are being evaluated, including disturbances in inflammatory responses, autonomic imbalance, and behavioral responses such as poor adherence [10], [11], [12]. Dysregulation of neuroendocrine function is another plausible pathway through which depressive symptoms and type-D personality might influence cardiovascular health [13], [14]. HPA axis dysregulation, resulting in elevated cortisol levels and loss of normal homeostatic negative feedback mechanisms, has been associated with hypertension, changes in body composition, hyperlipidemia, insulin resistance, impaired endothelial dysfunction, changes in hemostatic factors, and, if sustained over a long period, increase in the activity of proinflammatory cytokines [15]. One recent clinical study found that morning cortisol levels were positively associated with degree of stenosis on angiogram in women 3–6 months following ACS [16], and a prospective association between cortisol/testosterone ratio in men and the development of fatal and nonfatal CHD has been described [17].
Cortisol shows a robust diurnal pattern in healthy adults (peaking at 20–45 min after waking) and then steadily decreases through the day, with the lowest levels during the night and in the early morning. The increase in cortisol following waking is known as cortisol awakening response (CAR) and is largely independent of the underlying diurnal signal [18]. Elevated morning cortisol is a risk factor for clinical depression [19], [20], and a larger CAR is associated with depressive symptoms [21], low positive affect [22], high levels of perceived stress [23], and chronic job stress [24]. Smaller CARs have been observed in patients suffering from chronic fatigue [25] and in volunteers with self-reported health problems and chronic diseases [26].
Only one study to date has investigated the association of cortisol with depressive symptoms in a CHD population. Otte et al. [27] found a greater 24-h cortisol output in depressed outpatients with CHD than in nondepressed patients, independently of cardiac disease severity. However, the protocol used for cortisol sampling did not allow the subtleties of daily cortisol profile to be analyzed, and participants were all outpatients. No study has investigated cortisol and type-D personality in a CHD population, although one study found an association of greater cortisol reactivity with laboratory stressors in healthy volunteers [28]. Nor have the cortisol profiles of patients in the immediate aftermath of ACS been assessed.
The current study investigated salivary cortisol sampled several times over a 24-h period in patients hospitalized for ACS. We specifically focused on CAR as a dynamic measure that has been shown to be sensitive to psychosocial factors. Based on the previous literature, we hypothesized that the magnitude of CAR would be positively associated with levels of depression and type-D personality in patients following ACS, independently of other predictors of cortisol function such as age, sex, body mass index (BMI), and clinical factors.
Section snippets
Participants
Participants were recruited from four London hospitals within 5 days of admission as part of a larger study described elsewhere [29]. All patients were aged between 20 and 80 years old, with a diagnosis of ACS confirmed by electrocardiogram (ECG) changes (namely, new ST elevation of >0.2 mV in two contiguous leads in leads V1, V2, or V3, and new ST elevation of >0.1 mV in two other contiguous leads; ST depression of >0.1 mV in two contiguous leads in the absence of any QRS confounders, new left
Results
The demographic and clinical characteristics of the sample are shown in Table 1. The sample consisted of 66 men and 6 women aged 56.5±9.71 years, on average. The majority of participants (75.7%) were diagnosed with ST elevation MI and had not had a previous MI. Nearly half of the participants were smokers, and the number of coronary vessels found to be diseased on angiography averaged 1.18±0.87. Scores on the GRACE algorithm averaged 87.3, indicating a moderate risk of death in the first 6
Discussion
This study investigated salivary cortisol output while patients were still in the hospital after surviving a documented ACS. It was hypothesized that negative affective states experienced in the hospital would be associated with changes in cortisol profile. No effect was found for depressive symptoms, but participants with higher scores on measures of type-D personality showed larger CARs.
The lack of association between depression and HPA axis function is at odds with findings from the Heart
Acknowledgments
This study was supported by the British Heart Foundation. We are grateful to Dr. Sue Edwards for participation in data collection, Dr. Jean McEwan for contribution to study design and supervision, and the staff and patients of University College Hospital, St. George's Hospital, Southend and Kingston Hospitals.
References (43)
- et al.
Depression and ischemic heart disease: what have we learned so far and what must we do in the future?
Am Heart J
(2005) - et al.
Personality as independent predictor of long-term mortality in patients with coronary heart disease
Lancet
(1996) - et al.
Usefulness of type D personality in predicting five-year cardiac events above and beyond concurrent symptoms of stress in patients with coronary heart disease
Am J Cardiol
(2006) - et al.
Type D personality predicts death or myocardial infarction after bare metal stent or sirolimus-eluting stent implantation: a Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry substudy
J Am Coll Cardiol
(2004) - et al.
Depressive symptoms and the regulation of proinflammatory cytokine expression in patients with coronary heart disease
J Psychosom Res
(2005) - et al.
Cortisol and vital exhaustion in relation to significant coronary artery stenosis in middle-aged women with acute coronary syndrome
Psychoneuroendocrinology
(2002) - et al.
Neuroendocrine and cardiovascular correlates of positive affect measured by ecological momentary assessment and by questionnaire
Psychoneuroendocrinology
(2007) - et al.
Genetic factors, perceived chronic stress, and the free cortisol response to awakening
Psychoneuroendocrinology
(2000) - et al.
Awakening cortisol responses are influenced by health status and awakening time but not by menstrual cycle phase
Psychoneuroendocrinology
(2003) - et al.
Depression and 24-hour urinary cortisol in medical outpatients with coronary heart disease: The Heart and Soul Study
Biol Psychiatry
(2004)