Positive affect dimensions and their association with inflammatory biomarkers in patients with chronic heart failure

Abstract

Background

In cardiac patients positive affect has found to be associated with improved clinical outcomes, with reduced inflammation being one of the potential mechanisms responsible.

Methods

Positive affect was assessed using The Global Mood Scale (GMS), Positive and Negative Affect Schedule (PANAS), and Hospital Anxiety and Depression Scale (HADS) in patient with chronic heart failure (N = 210; 67 ± 9 years, 79% men). Markers of inflammation (TNFα, sTNFr1, sTNFr2, IL-6 and CRP) were measured and averaged at three consecutive time points.

Results

The positive affect dimensions of the GMS and PANAS were significantly associated with lower averaged levels of sTNFr2, TNFα and IL-6 (p < .1), even after adjustment for clinical and lifestyle confounders. Positive affect of the HADS was significantly associated with lower averaged levels of hsCRP (p < .1), but was no longer significant after correction for lifestyle confounders and depressive symptoms.

Conclusion

Positive affect is associated with reduced inflammation in patients with heart failure.

Introduction

There is emerging evidence that emotions play a key role in linking psychological stress to physical health (Cohen and Pressman, 2006, Dockray and Steptoe, 2010). Apart from the detrimental effects of negative affect, such as anger, depression, and anxiety, there is a growing interest in the role of positive affect as a potentially protective factor in the progress of chronic disease (Pelle et al., 2011). Positive affect is defined as feelings that reflect a state of high energy, full concentration and a level of pleasurable engagement with the environment, such as joy, happiness and contentment (Cohen and Pressman, 2006). Positive affect can confer benefit to individuals beyond the feeling of well-being, given that it has been associated with an overall prolonged healthy life expectancy (Chida and Steptoe, 2008, Steptoe et al., 2007), reduced blood pressure (Brummett et al., 2009, Raikkonen et al., 1999, Steptoe et al., 2007), a higher heart rate variability (Bhattacharyya et al., 2008) and a reduced risk for stroke, coronary heart disease (Kubzansky and Thurston, 2007) and hypertension (Pelle et al., 2011, Steptoe et al., 2007). The mechanisms responsible for the link between positive affect and improved health ought to be found in behavioral and biological pathways such as a healthy lifestyle and inflammation (Dockray and Steptoe, 2010). Assuming the mechanisms between negative and positive affect are similar and acting in opposite manners, positive affect is expected to render an anti-inflammatory effect as negative affect has been associated with higher pro-inflammatory levels (Ferketich et al., 2005, Johansson et al., 2011, Parissis et al., 2004). Indeed, previous studies have found positive affect to be associated with functional changes of the immune system (Cohen et al., 1999, Cohen et al., 2003, Cohen et al., 2006, Marsland et al., 2006), and specifically also with lower levels of the stress hormones epinephrine, norepinephrine and cortisol (Pressman and Cohen, 2005). These hormones are important regulators of immune functioning, and subsequently of the level of inflammatory biomarkers (i.e. Interleukin-6 (IL-6), Tumor necrosis factor alpha (TNFα), C-reactive protein (CRP)) in the body. (Pressman and Cohen, 2005). IL-6 and CRP are crucial in the regulation of thrombopoiesis, the acute phase response, and the formation of fibrosis in cardiac tissue (Hirschfield and Pepys, 2003). Several studies have observed an association between positive affect and levels of IL-6 and CRP (Brydon et al., 2009, Dockray and Steptoe, 2010, Friedman et al., 2007, Prather et al., 2007, Steptoe et al., 2008). Some studies found an inverse association between positive affect and levels of IL-6 in healthy adults (Friedman et al., 2007, Prather et al., 2007), women (Steptoe et al., 2008) or men (Brydon et al., 2009), adjusting for age, ethnicity, socioeconomic status, body mass index (BMI), smoking and depressed mood. Furthermore, positive affect was associated with reduced levels of the inflammatory marker CRP in healthy women from the Whitehall II study, but not in men (Steptoe et al., 2008). There are also several studies linking mood to TNFα and its receptors, which also play a pivotal role in relation to HF as cells within the myocardium are able to synthesize and release TNF-α in response to cardiac stress, such as left ventricular pressure, or volume overload. TNF-α release then leads to an increase in soluble receptors sTNFr1 and sTNFr2 which act as immunomodulatory elements (Aderka et al., 1992). However, most studies on TNFα and its receptors have used negative affect states such as depression (Kop et al., 2011), and did not further investigate positive affect.

Despite several studies reporting an association between positive affect and lower levels of inflammation, the association is not always found for all cytokines (Prather et al., 2007), and sometimes even entirely absent (Andreasson et al., 2012). An explanation for this could be the use of different instruments for positive affect in a variety of populations, making it difficult to compare the results. Moreover, since there seems to be little agreement on what is actually meant by positive affect (Cohen and Pressman, 2006), one can also not just assume that what these instruments measure is identical. On top of that, many studies examining the relation between positive affect and prognosis or survival are limited by a lack of control for potential confounders such as negative affect. Therefore the aim of this study was first of all, to examine the differences in three positive affect constructs which are commonly used in cardiovascular populations, i.e., the Global Mood Scale (GMS), the Positive and Negative Affect Schedule (PANAS) and the positive affect dimension of the Hospital Anxiety and Depression Scale (Cohen and Pressman, 2006), in a single patient population, and second, to examine whether these positive affect constructs differ in their association with five inflammatory biomarkers (e.g., TNFα, sTNF1, sTNFr2, IL-6, CRP) using a prospective mixed model, additionally correcting for depressive symptoms.