Self-rated health and vital exhaustion, but not depression, is related to inflammation in women with coronary heart disease
Introduction
Recently, there has been an increasing appreciation that psychological factors may play an important role in development and prognosis of coronary heart disease (CHD). Among others, three partly overlapping constructs have been related to increased CHD morbidity and mortality in population-based studies and with adverse outcomes in existing CHD: (1) depression (Frasure-Smith et al., 1995, Hemingway and Marmot, 1999), (2) self-rated health (Bosworth et al., 1999, Moller et al., 1996), and (3) a relatively new construct, that of vital exhaustion which is characterized by a state of unusual fatigue, loss of energy, increased irritability, and feelings of demoralization (Appels and Mulder, 1988, Koertge et al., 2002, Kop et al., 1994). Little is known about the mechanisms responsible for this association but immune activity appears to be a potential pathway (Carney et al., 2002, Grippo and Johnson, 2002, Joynt et al., 2003, Kop and Cohen, 2001).
Evidence is growing that links immune activity with CHD (Ross, 1999). Increased inflammation as reflected by elevated levels of acute-phase reactants and pro-inflammatory cytokines, especially that of C-reactive protein (CRP) and interleukin-6 (IL-6), have been associated with increased cardiovascular morbidity and mortality among general population cohorts (Jenny et al., 2002, Pradhan et al., 2002, Ridker et al., 2000a, Ridker et al., 2000b), and with poor prognosis among survivors of acute coronary events (Biasucci et al., 1999, Blankenberg et al., 2002, Haverkate et al., 1997, Lindahl et al., 2000, Lindmark et al., 2001, Liuzzo et al., 1994, Tomoda and Aoki, 2000).
Similarly, inflammation and pro-inflammatory cytokines have also been linked to different psychological factors, especially to depression (see Anisman and Merali, 2003, Pollak and Yirmiya, 2002 for review). Infectious or autoimmune diseases, as well as administration of cytokines, induce a symptomatology often referred to as “sickness behavior”—characterized by fatigue, loss of energy, anorexia, difficulties to concentrate, and anhedonia—that bears a strong resemblance to depression (Dantzer, 2001, Konsman et al., 2002, Späth-Schwalbe et al., 1998). This effect of cytokines can be prevented by antidepressant treatment (Musselman et al., 2001). It was also suggested that the administered cytokines induce changes in the neuroendocrine and central neurotransmitter systems reminiscent of those implicated in depression (Anisman and Merali, 2003, Wichers and Maes, 2002). Furthermore, antidepressants have immunmodulatory properties (Szelenyi and Selmeczy, 2002), and successful treatment of depression can be accompanied by a decrease in inflammation (Mohr et al., 2001). Moreover, depressed or vitally exhausted individuals show elevated levels of circulating (Danner et al., 2003, Dentino et al., 1999, Glaser et al., 2003, Kop et al., 2002, Miller et al., 2002, Tiemeier et al., 2003, Van Der Ven et al., 2003) and stimulated cytokines (Suarez et al., 2003), as well as reduced glucocorticoid sensitivity of monocyte IL-6 production (Wirtz et al., 2003). However, much less attention has been paid to the link between depression or vital exhaustion and inflammation in CHD patients (Carney et al., 2002). In addition, we are not aware of any studies that assess the relation between self-rated health and cytokines in a CHD patient population. Accordingly, to further elucidate the immunological bases for the association between psychological factors and CHD, we examined the relation between depression, vital exhaustion, and self-rated health, and the circulating levels of IL-6, interleukin-1 receptor antagonist (IL-1ra) and CRP in women with CHD.
Section snippets
Study population
In this cross-sectional study, we included patients from a randomized controlled intervention trial. The intervention comprised a rehabilitation program specifically designed for women with CHD. The program focused on providing information about well-established risk factors, including psychological ones and how to deal with them (Burell and Granlund, 2002). The original study population consisted of 247 women that had survived acute myocardial infarction (AMI) or undergone a revascularization
Results
Out of the 235 patients enrolled in the study three had died between randomization and present assessment, all from the control group, leaving 232 eligible patients, 113 in the intervention group, and 119 controls.
In Table 1, we present the distribution of study variables according to group assignment. The mean age was 62.9 ± 8.8 years for the entire cohort, and 63.3 ± 8.7 years for the controls, and 62.5 ± 8.9 years for participants in the intervention group. The mean score for depression was 9.49
Discussion
We investigated the relationships of CRP, IL-6, and IL-1ra levels to three related constructs which assess an individual’s subjective well-being in CHD. Vital exhaustion and self-rated health showed an independent association with IL-6. Their relation to CRP was weaker and only marginally significant in most of the multivariate models. There was no evidence for a relation between depressive symptoms and inflammatory markers.
Growing evidence implicates pro-inflammatory cytokines in the
Conclusion
We investigated the relationship between inflammation and subjective well-being in women CHD patients, as both measures of well-being and inflammatory markers have been found to be predictive for adverse outcomes in CHD patients. Our findings, that inflammatory activity, reflected by the IL-6 and CRP levels, is associated with vital exhaustion and self-rated health, provides further evidence for a possible psychoneuroimmune link between mental state and CHD. These observations also raise the
Acknowledgments
This study was supported by grants from the Ansgarius Foundation, the Belvén Foundation, the Swedish Heart and Lung Foundation, the Public Health Committee and Expo-95 of Stockholm County Council, Swedish Medical Research Council (Project 19X-11629), and the Vardal Foundation, Stockholm, Sweden.
References (61)
- et al.
A questionnaire to assess premonitory symptoms of myocardial infarction
Int. J. Cardiol.
(1987) Depression and coronary heart disease: Observations and questions
J. Psychosom. Res.
(1997)- et al.
Depression induced by treatment with interferon-alpha in patients affected by hepatitis C virus
J. Affect. Disord.
(2002) - et al.
Depression as a risk factor for cardiac mortality and morbidity: A review of potential mechanisms
J. Psychosom. Res.
(2002) Cytokine-induced sickness behavior: Where do we stand?
Brain Behav. Immun.
(2001)- et al.
Biological mechanisms in the relationship between depression and heart disease
Neurosci. Biobehav. Rev.
(2002) - et al.
Depression and cardiovascular disease: Mechanisms of interaction
Biol. Psychiatry
(2003) - et al.
Exercise-induced immune changes—an influence on metabolism?
Trends Immunol.
(2001) - et al.
Cytokine-induced sickness behaviour: Mechanisms and implications
Trends Neurosci.
(2002) - et al.
Inflammation and coagulation factors in persons >65 years of age with symptoms of depression but without evidence of myocardial ischemia
Am. J. Cardiol.
(2002)
Clinical depression and inflammatory risk markers for coronary heart disease
Am. J. Cardiol.
Inflammatory markers and depressed mood in older persons: Results from the Health, Aging and Body Composition Study
Biol. Psychiatry
Immunomodulatory effect of antidepressants
Curr. Opin. Pharmacol.
Prognostic value of C-reactive protein levels within six hours after the onset of acute myocardial infarction
Am. Heart J.
Cytokines, stress and depressive illness: Brain–immune interactions
Ann. Med.
Excess fatigue as a precursor of myocardial infarction
Eur. Heart J.
Inflammation, depressive symptomtology, and coronary artery disease
Psychosom. Med.
The nature of the depressive symptomatology preceding myocardial infarction
Behav. Med.
An inventory for measuring depression
Arch. Gen. Psychiatry
Increasing levels of interleukin (IL)-1Ra and IL-6 during the first 2 days of hospitalization in unstable angina are associated with increased risk of in-hospital coronary events
Circulation
The association between self-rated health and mortality in a well-characterized sample of coronary artery disease patients
Med. Care
Women’s hearts need special treatment
Int. J. Behav. Med.
The association of plasma IL-6 levels with functional disability in community-dwelling elderly
J. Gerontol. A Biol. Sci. Med. Sci.
Association between depression and elevated C-reactive protein
Psychosom. Med.
Association of interleukin-6 and other biologic variables with depression in older people living in the community
J. Am. Geriatr. Soc.
Change in muscle strength explains accelerated decline of physical function in older women with high interleukin-6 serum levels
J. Am. Geriatr. Soc.
Depression and 18-month prognosis after myocardial infarction
Circulation
Mild depressive symptoms are associated with amplified and prolonged inflammatory responses after influenza virus vaccination in older adults
Arch. Gen. Psychiatry
Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group
Lancet
Cited by (130)
How is inflammation biology truly associated with depression in patients with stable coronary heart disease?: Insights from the heart and Soul study
2024, Brain, Behavior, and Immunity - HealthPatient global assessment and inflammatory markers in patients with idiopathic inflammatory myopathies – A longitudinal study
2024, Seminars in Arthritis and RheumatismSex differences in the association of vital exhaustion with regional fat deposition and subclinical cardiovascular disease risk
2022, Journal of Psychosomatic Research