It is estimated that 16 million American adults have coronary heart disease (CHD). CHD remains the leading cause of death in the United States with 652,091 registered deaths in 2005 [1
]. To date, multiple longitudinal and cross-sectional studies have examined the association of CHD with psychological functioning, particularly depression [2
]. Over 100 studies have investigated this relationship, thus providing evidence that depression is prevalent (18% to 60%) in patients with CHD. This comorbidity has significant adverse effects on the course and outcome of CHD [4
]. Depressed patients are twice as likely as nondepressed patients to have a major cardiac event within 12 months of the diagnosis of coronary artery disease [8
]. In addition, the risk of mortality is greater in depressed patients compared to nondepressed after the following events: CHD [4
], acute myocardial infarction [9
], an episode of unstable angina [10
], or CABG [4
Although the relationship between depression and cardiac events is well established, the mechanism underlying this relationship remains unclear [11
]. However, three lines of evidence suggest that altered autonomic nervous system (ANS) activity in depressed patients might be responsible for the increased risk of mortality and medical morbidities in patients with CHD. First line of evidence originates from early reports of ANS dysregulation in depression was found in studies of medically ill patients with major depressive disorder (MDD). These studies found elevated levels of plasma and urinary catecholamines, primarily norepinephrine (NE), in depressed patients compared with controls [12
]. These findings are significant because the concentrations of plasma NE generally parallel the level of activity of the sympathetic nervous system (SNS) and are highly correlated with sympathetic neural activity [14
A second line of evidence is based on the consistent findings that resting Heart Rate (HR) is higher in depressed than nondepressed patients [14
]. Depression is also associated with exaggerated HR response to physical and psychological stressors in both medically well individuals [17
] as well as in patients with CHD [18
]. As regulation of HR occurs primarily through a reciprocal interaction of the sympathetic and parasympathetic nervous system, and given that one of the functions of ANS is to regulate HR, elevated HR suggests dysregulation of cardiac ANS function.
A third line of evidence is based on studies reporting decreased Heart Rate Variability (HRV) among depressed patients compared to nondepressed controls [8
]. Over the last two decades, HRV has emerged as an important marker for examining the continuous interplay between the parasympathetic and sympathetic influences on HR that yields information about autonomic flexibility [21
]. Increased HRV has been used as a marker of increased vagal activity and has been consistently associated with greater capacities to regulate stress, emotional arousal, and attention [22
] while low HRV has been associated with excessive cardiac sympathetic modulation, inadequate parasympathetic modulation, or both [23
]. A number of studies have found HRV to be lower in depressed psychiatric patients compared to controls [20
]. There is even greater evidence that HRV is lower in depressed than nondepressed patients with CHD [24
In summary, there is considerable evidence of autonomic cardiovascular dysregulation in depressed patients as well as in patients with CHD. However, it is unknown whether patients with CHD and depression have greater ANS dysregulation relative to patients with either depression or CHD alone (i.e., comorbidity versus single morbidity). It is also unknown whether ANS dysregulation explains the increased morbidity and mortality in patients with both disorders. Thus, the purpose of this study was twofold. First, we compared three markers of ANS function in four groups of patients: 1) Patients with coronary heart disease and depression (CHD/DEP), 2) Patients without CHD but with depression (NonCHD/Dep), 3) Patients with CHD but without depression (CHD/NonDep), and 4) Patients without CHD and depression (NonCHD/NonDep). Second, we investigated the association of ANS activity (HR, HRV, and plasma NE levels) impact of depression and autonomic nervous system activity on CABG outcomes.
Second, we investigated the association between these markers of ANS function and group classification in cardiac patients (i.e., CHD/DEP vs. CHD/NonDep) and CABG outcomes (i.e., in-hospital length of stay and patient's type of discharge (i.e., routine or nonroutine), while holding constant potential differences in medical (e.g., diabetes, history of myocardial infarction, etc.) and sociodemographic (e.g., age, gender, etc.) variables. We hypothesized that patients in the CHD/Dep group will have the greatest dysregulation in autonomic function while patients in the NonCHD/NonDep group will have the least amount of autonomic dysregulation compared to the other 2 groups. We also hypothesized that ANS markers and group classification in cardiac patients will significantly predict in-hospital length of stay and patient's type of discharge. Specifically, there will be a significant positive association between HR and plasma NE levels and in-hospital length of stay. There will be a significant negative association between HRV and in-hospital length stay. In addition, patients in the CHD/Dep group will more likely be discharged non-routinely discharged following a CABG operation than those with CHD only. Both of these hypotheses reflect a possible additive effect of depression and heart disease on ANS dysregulation.