This page contains a Flash digital edition of a book.
Mind & Brain, the Journal of Psychiatry

meta-analysis of 23 randomized controlled trials that eval- uated the impact of adding psychosocial interventions to standard cardiac rehabilitation regimens, Linden et al33 observed that, during the first 2 years of follow-up, lack of psychosocial intervention was associated with greater rates of mortality and recurrent MI.

PROPOSED MECHANISMS EXPLAINING THE LINK BETWEEN ANXIETY CV DISEASE Mechanisms linking anxiety to CV disease can be categor-

ized into two pathways: neurohormonal and behavioral pathways. Below, we discuss the significance and evidence in support of both pathways.

Neurohormonal pathway Activation of the sympathetic nervous system, as manifested

by impaired vagal control, reduction in heart rate variability,34 elevated levels of proinflammatory cytokines,5 and hypercor- tisolemia from activation of the hypothalamic pituitary axis (HPA),35 is increasingly recognized as a favorable link between anxiety and CV disease.3436 Epidemiological evi- dence indicates that negative emotions have cumulative pathophysiological effects that can ultimately lead to CHD events through damage from persistent activation of the neurohormonal systems and other mechanisms.3739 In- creased output from the sympathetic nervous system and HPA can induce a wide variety of physiologic responses.22 Studies have shown that the number of lymphocyte b- adrenergic receptors7981 and b-adrenergic- mediated cyclic AMP generation are decreased among patients with anxiety disorder, especially in the context of panic disorder.82,83 Aronson et al80 demonstrated a negative correlation between trait anxiety and the number of lymphocyte b-adrenergic receptors. Among patients experiencing panic attacks, base- line catecholamine and 3-methoxy-4-hydroxyphenylglycol levels appear to be either normal or mildly elevated.8486 Following infusion of isoproterenol, a smaller change in the heart rate was observed among patients with panic disorder,87 suggesting that chronic anxiety, by increasing sympathetic outflow, can lead to b-adrenergic receptor downregulation.

Data from the Normative Aging Study, which previously identified an excess risk of CHD associated with anxiety, also showed a link between high levels of anxiety and reduced heart rate variability34. With increased anxiety symptoms, there was a corresponding decrease in heart rate variability. This finding supports studies suggesting that the association of anxiety with sudden cardiac death, but not MI,17,18,25 may be related to ventricular arrhythmias. Autonomic alteration could involve either increased sympathetic stimulation, which has been linked to the occurrence of arrhythmias and sudden death,88 or impaired vagal control, which has also been linked to increased cardiac mortality.89,90 Specifically, re- duced vagal control has been linked to impaired vagally mediated baroreflex control of the heart.91 Such impairment appears to be a particularly important risk factor for sudden death.92,93 Watkins et al94 reported reduced baroreflex cardiac

M&B 2011; 2:(1). July 2011 34

control among patients with anxiety, but prospective work is needed to determine whether this is a common operative mechanism for sudden deaths among patients with anxiety syndromes. Consistent with these findings, we previously observed that insomnia, which has been shown to be a form of chronic stress and sympathetic disorder, is in part responsible for the association between anxiety and CV symptoms.14 Furthermore, an atherogenic pathway, pro- moted by recurring activation of the neurohormonal system with subsequent endothelial injury and atherosclerosis, has also been suggested.45

Behavioral pathway Various lifestyle behaviors, including unhealthy diet, physi-

cal inactivity, and smoking, promote the development and clinical manifestations of CHD.22 Studies suggest that individuals with anxiety disorders are prone to unhealthy lifestyle behaviors.16,95 Negative emotions may exacerbate disease progression or reduce survival, either via direct physiological effects or through reduced compliance with recommended medical regimens.96,97 Among patients with CHF, negative emotions are associated with unhealthy life- style,98 and have been shown to be predictors of dietary and exercise adherence.11,99,100

Riegel et al101 suggest that the impact of anxiety on cardiac

diseases may be related to the associated poor uptake of self- care behaviors. Anxiety may impair energy, cognition, and motivation to engage in self-care behaviors.96 Patients with high levels of anxiety have difficulty making lifestyle changes, coping with challenges, and encounter more problems during cardiac rehabilitation.102104 Evidence suggests that anxiety is a predictor of poor adherence to lifestyle change recommen- dations and adherence to medical therapy.105 Among highly anxious patients with recent hospitalization for acute exacer- bation of CHF, adherence to a number of self-care behaviors was extremely poor.11 In that study, only 9% of patients reported self-monitoring for symptoms of worsening CHF, 14% of patients were weighing themselves daily, 31% could not name even one symptom of CHF, and only 34% of patients were taking all the medications as prescribed. These findings suggest that unhealthy lifestyle behaviors may contribute to cardiac risks associated with anxiety.

A general effect of distress

The clustering of psychosocial factors and the similarity of findings between the three negative emotions and CV outcome raise the question as to whether the effects of anxiety, depression, or anger are unique, or just a general effect of distress. It has been suggested that general distress shared by these negative emotional states is a key factor,106 but little work has been done to tease apart these relation- ships. Recently, the uniqueness of these three negative emotions as risk factors for incident CHD was explored in a prospective study of a disease-free population, which was followed for 11 years.96 General stress, anxiety, and depres- sion measured at study entry were each strong predictors of incident CHD over the follow-up period. At the end of the

Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89