Author + information
- Christiane Waller, MD∗ (, )
- Johann Bauersachs, MD,
- Uta Hoppmann, MS,
- Julia Höch, MS,
- Sabrina Krause, MS,
- Franziska Szabo, MS,
- Harald Engler, PhD,
- Edit Rottler,
- Christoph Herrmann-Lingen, MD and
- Harald Gündel, MD
- ↵∗Clinic of Psychosomatic Medicine and Psychotherapy, Medical University of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany
Both depression and psychosocial stress are associated with coronary artery disease (CAD) (1). However, the precise underlying mechanisms have not been elucidated fully. Cortisol is involved in the pathophysiological process of inflammation and atherosclerosis (2), but evidence directly linking depression and social stress with cortisol in CAD patients is limited. Bhattacharyya et al. (3) revealed a flatter diurnal cortisol slope in depressed (+CAD) compared with nondepressed (-CAD) patients, but found no relationship between the diurnal cortisol slope and depression in people without CAD (3). Our study aimed to elucidate the social stress-induced cortisol response in (+CAD) and (-CAD) patients in relation to depressive symptoms and high-sensitivity C-reactive protein (hsCRP). We hypothesized that depressed (+CAD) patients would show a blunted cortisol stress response with a close relation to systemic inflammation.
We investigated 91 subjects, 46 of whom experienced CAD with (21 [+D+CAD]) or without depressive symptoms (25 [-D+CAD]) and were compared with 22 depressed patients without CAD (+D-CAD) and 21 healthy subjects (-D-CAD). The German version of the depression subscale of the Hospital Anxiety and Depression scale (HADS) was used to rate symptom levels of depression (cutoff, <8). In (+D+CAD) and (+D-CAD) patients, Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Version IV (SCID-IV) revealed major depression in 25, major depression in the last months in 11, and dysthymia in 7 patients. In the (-D-CAD) and (-D+CAD) groups, SCID-IV showed no abnormalities. Participants were scheduled to the laboratory until 9:00 am and a venous catheter was inserted before a 60-min resting period. We applied the Trier Social Stress Test (TSST) combining a social and cognitive stressor composed by a 5-min anticipatory stress after a short introduction and a 5-min mock job interview and 5-min mental arithmetic task in front of an audience (4). Blood samples were obtained immediately before (cortisol, hsCRP) and at 1, 5, 15, 30, and 60 min (cortisol) after the TSST, were centrifuged (3,000 rpm, 10 min, 4°C) and stored at -80°C. Cortisol was measured by a competitive immunoassay (Siemens Healthcare, Erlangen, Germany). Using an enzyme-linked immunosorbent assay (IBL International, Hamburg, Germany), hsCRP was measured. Intra-assay and inter-assay variabilities were below 7%.
All data (mean ± standard error) were controlled for age, gender, body mass index, β-blockers, and antidepressants as covariates. Greenhouse–Geisser correction for repeated measures was applied. Other cardiovascular medications were tested separately to eliminate potential medication-related effects. Univariate analyses of covariance (ANCOVAs) revealed significant differences in baseline cortisol between (+D+CAD) and (-D+CAD) patients (+D+CAD [7.70 ± 0.85], -D+CAD [10.78 ± 1.10], +D-CAD [9.96 ± 1.01], -D-CAD [9.30 ± 0.98]), F(1;43) = 6.07, p = 0.019. Using ANCOVAs for repeated measures with four characteristics (4 groups, independent variable) and cortisol (6 repetitions, repeated dependent variable), we found significant group and group-by-stress effects. Both (+CAD) groups showed a blunted cortisol stress response compared with the (-CAD) groups (Figure 1). We found no group differences in hsCRP (3.33 ± 0.89 mg/l [+D+CAD], 2.09 ± 1.07 mg/l [-D+CAD], 1.61 ± 1.12 mg/l [+D-CAD], and 1.50 ± 1.19 mg/l [-D-CAD]). Partial correlations revealed that HADS depression scores were negatively related to baseline cortisol in (+CAD) (r = -0.346, p = 0.031) compared with (-CAD) patients (r = -0.005; p = NS), whereas no relation was found between HADS depression and hsCRP ([+CAD] r = 0.078; [-CAD] r = 0.046; p = NS). Baseline cortisol was negatively related to hsCRP (r = -0.431; p = 0.027) in the (+CAD) groups, but not in the (-CAD) groups (r = -0.103; p = NS).
Our findings indicate that a blunted cortisol stress response and depression-induced baseline hypocortisolism in (+CAD) patients may play a key role in the progression of atherosclerosis and mortality due to an increased vulnerability to inflammation and autoimmunity (5). Strengths of our study include the comparisons of 4 groups in a well-validated stress paradigm, which makes it possible to delineate unique effects of CAD and depression. Further research is needed to evaluate our cross-sectional findings in a longitudinal study design.
Please note: The authors gratefully acknowledge the SPIRR-CAD study group funded by the German Research Foundation (Deutsche Forschungsgemeinschaft; DFG) for help in recruiting the CAD patients group. They also thank Markus Becker for his help in recruiting depressed patients and Reinhold Kilian for his methodological support. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
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