In Canada and in the United States, over 6% of adults aged 20 years or older live with coronary artery disease (CAD), the most common form of cardiovascular disease [
1,
2]. Along with its elevated prevalence, CAD is also one of the costliest diseases in both countries, with annual direct and indirect costs reaching 219$ billions a year in the United States [
2‐
4]. Although the incidence and mortality rates associated with CAD have decreased in the last decades, it remains one of the leading causes of mortality, hospitalization and disability-adjusted life years lost worldwide [
1,
5,
6].
A variety of interventions may be used to manage the potential consequences of CAD and improve the prognosis of patients [
7‐
9]. Given that up to 90% of the myocardial infarction risk is attributable to nine modifiable risk factors (e.g., cholesterol levels, hypertension, diabetes, smoking, obesity, physical inactivity, alcohol use, diet and psychosocial factors), comprehensive risk factor management programs and cardiac rehabilitation are essential to improve outcomes in patients with CAD [
8,
10,
11]. The management of psychosocial risk factors represents a particular challenge: while decades of research have demonstrated their importance in patients with CAD, the nature and implications of the relationship between CAD and anxiety disorders is not as well understood as that of other CAD risk factors [
12‐
17]. Although much of the research to date has focused on the role of depression, a growing number of studies suggest that anxiety may also lead to negative outcomes in this population [
18‐
22].
Anxiety and coronary artery disease
Elevated anxiety has been independently associated with a 36–88% increase in the risk of adverse cardiac events in patients with CAD [
22‐
32]. However, the relationship between anxiety, CAD and CAD-related mortality remains unclear [
33]. This may be partly due to the fact that anxiety, particularly anxiety disorders, remains understudied in the context of CAD [
33]. One important issue is that most of the studies on this topic assessed anxiety with self-reported questionnaires [
33]. This approach alone cannot be used to diagnose anxiety disorders which, due to their severity and chronic course, are more likely to have a significant impact on CAD prognosis [
21,
28].
Two anxiety disorders, generalized anxiety disorder (GAD) and panic disorder (PD), are of particular interest and importance in patients with CAD as their prevalence rates among this clinical population (24 and 53% respectively), are up to 15 times higher than those in the general population [
21,
33‐
39]. In patients with CAD, the presence of these disorders is also associated with an increased risk of major cardiac events, greater disability, higher psychological distress and lowered quality of life [
21,
39‐
44]. Both disorders are also characterized by an increased suicidal risk and multiple and often unproductive medical consultations [
45‐
50] as well as incident CAD and cardiac events [
22,
51,
52]. Without treatment, PD and GAD have a chronic course and worsen over time, which negatively influence their prognosis and treatment response [
46,
53‐
55].
Diagnosing anxiety disorders such as GAD and PD in patients with CAD can be challenging as there is a significant overlap in the somatic symptoms of both conditions (e.g. chest pain, dizziness, dyspnea, palpitations and tiredness) [
20,
21,
33,
35,
56]. This may explain why anxiety disorders have been found to be more prevalent in the few studies in which they were diagnosed using structured interviews (the gold standard for psychiatric diagnoses) conducted by trained mental health professionals [
33]. Furthermore, a single assessment point, as was used in several reviewed studies, might not be reliable in order to adequately identify pathological anxiety in patients with CAD [
20‐
22,
24,
25,
27,
31‐
33]. Indeed, some authors have expressed concerns that assessing anxiety disorders shortly after a cardiac or life-threatening event may lead to false positives [
28,
35]. In addition, the onset of a chronic illness such as CAD and dealing with its consequences are risk factors for the development of GAD and PD [
57] and could lead to an elevated incidence of these disorders in the following months and years. Thus, further prospective studies using validated structured interviews and a robust methodology to assess the prevalence and incidence of PD and GAD in patients with CAD are needed [
33].
Possible mechanisms linking panic disorder and generalized anxiety disorder with CAD prognosis
Though still unclear, physiological and behavioral pathways have been proposed to explain how anxiety disorders and CAD influence each other and subsequently lead to poorer outcomes. Part of the association between CAD and anxiety disorders may be explained by physiological factors, such as increased inflammation [
20,
21,
36,
39,
58]. Anxiety disorders are also associated with higher rates of hypertension, obesity, diabetes and dyslipidemia, which all increase the cardiovascular risk [
21,
29,
59]. PD and GAD have also been linked to poorer health behaviors [
20,
21,
36,
60‐
64]. For instance, the likelihood of alcohol use disorder, either dependence or abuse, is 79–83% higher in patients with GAD or PD than in patients without these disorders [
65,
66]. These anxiety disorders are also associated with a 50–90% increased risk of daily smoking and nicotine dependence as well as low levels of physical activity [
61,
63,
64,
67‐
70]. Furthermore, high levels of anxiety have been associated with non-attendance and non-completion of cardiac rehabilitation programs and non-adherence to cardiac medication [
64,
70‐
75]. Consequently, another part of the association between anxiety disorders and CAD could be explained by the negative influence of these disorders on health behaviors and adherence to evidence-based risk-reducing recommendations and treatments for CAD [
20,
21,
56,
64,
70,
75].
Summary
Despite the recommendations of the American Heart Association in 2014 [
18], very few studies have prospectively investigated the independent role and differential impacts of anxiety disorders on cardiovascular outcomes in patients with established CAD [
33,
76]. While some studies assessed the prevalence and prognostic implications of GAD in patients with CAD, to our knowledge, no prospective study has documented the potential consequences of PD on these same outcomes.
Anxiety disorders, and more specifically PD and GAD, are associated with a wide array of unhealthy behaviors, but the prevalence and persistence of such behaviors in patients with CAD remain unknown. Moreover, no study has investigated the role of PD and GAD on enrollment, participation and adherence to cardiac rehabilitation. Finally, only one study accounted for both medical and behavioral risk factors while assessing the effects of GAD on adverse cardiac outcomes in patients with CAD [
31]. This low number of studies combined with concerns regarding diagnostic accuracy in most of them severely limit the interpretation of the data available on this issue, underscoring the importance of further research on the prognostic significance of PD and GAD in patients with CAD.