Self-rated health and vital exhaustion, but not depression, is related to inflammation in women with coronary heart disease

Abstract

Poor subjective well-being has been associated with increased coronary heart disease (CHD) morbidity and mortality in population-based studies and with adverse outcomes in existing CHD. Little is known about the mechanisms responsible for this association, but immune activity appears to be a potential pathway. Despite the growing evidence linking immune activity to subjective feelings, very few studies have examined patients with CHD, and the results are conflicting. We examined consecutive women patients hospitalized for acute myocardial infarction, and/or underwent percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. We assessed depression, vital exhaustion, and self-rated health by questionnaires. Circulating levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and interleukin-1 receptor antagonist (IL-1ra) concentrations were determined. After controlling for potential confounding factors there was a significant positive correlation between IL-6 levels and vital exhaustion and poor self-rated health. The association between hsCRP and vital exhaustion and self-rated health was borderline significant. In contrast, the correlations between psychological factors and IL-1ra levels were weak and non-significant, as were the correlations between inflammatory markers and depression. Similar relationships between the inflammatory markers and the measures of psychological well-being were obtained when the latter ones were categorized into tertiles. In conclusion, inflammatory activity, assessed by IL-6 and hsCRP levels, was associated with vital exhaustion and self-rated health in CHD women. These findings may provide further evidence for a possible psychoneuroimmune link between subjective well-being and CHD. Our observations also raise the possibility that a cytokine-induced sickness response in CHD may be better represented by constructs of vital exhaustion and self-rated health than of depression.

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.