Depressive Symptoms and 24-Hour Urinary Norepinephrine Excretion Levels in Patients With Coronary Disease: Findings From the Heart and Soul Study

Abstract

Objective-Depressive symptoms are associated with an increased risk of cardiac events in patients with heart disease. Elevated catecholamine levels may contribute to this association, but whether depressive symptoms are associated with catecholamine levels in patients with heart disease is unknown. Method-The authors examined the association between depressive symptoms (defined by a PatientHealth Questionnaire score ≥10) and 24-hour urinary norepinephrine, epinephrine, and dopamine excretion levels in 598 subjects with coronary disease.Results-A total of 106 participants (18%) had depressive symptoms. Participants with depressive symptoms had greater mean norepinephrine excretion levels than those without depressive symptoms (65 μg/day versus 59 μg/day, with adjustment for age, sex, body mass index, smoking, urinary creatinine levels, comorbid illnesses, medication use, and cardiac function). In logistic regression analyses, participants with depressive symptoms were more likely than those without depressive symptoms to have norepinephrine excretion levels in the highest quartile and above the normal range. Depressive symptoms were not associated with dopamine or epinephrine excretion levels.Conclusions-In patients with coronary disease, depressive symptoms are associated with elevated norepinephrine excretion levels. Future longitudinal studies are needed to determine whether elevations in norepinephrine contribute to adverse cardiac outcomes in patients with depressive symptoms.Coronary disease and major depression are the two leading causes of disability worldwide (1). Depressive symptoms occur in about 20% of patients with coronary disease (2,3) and are associated with an increased risk of future cardiac events and mortality (4-7). However, the mechanisms linking depressive symptoms with subsequent cardiac events are unknown (8).Enhanced activity of the sympathetic nervous system with increased concentrations of catecholamines has been proposed as one possible mechanism by which depressive symptoms may increase morbidity and mortality (7-9). This hypothesis is based on evidence suggesting that depressed patients without heart disease have elevated catecholamine levels (10-12). Previous studies have also found alterations of the sympathetic nervous system in depressed NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript patients with coronary heart disease, including increased heart rate (13) and decreased heart rate variability (14). High catecholamine levels can damage cardiac myocytes (15,16) and have been associated with cardiac events and mortality in a variety of clinical and population-based samples (17)(18)(19)(20)(21)(22). Thus, altered autonomic tone may contribute to adverse cardiac outcomes in patients with depression.The Heart and Soul Study is an ongoing prospective cohort study of psychosocial factors and health outcomes in patients with coronary disease (3). We examined the association of depressive symptoms with 24-hour levels of uri-nary norepinephrine, epinephr...

Association of a Serotonin Transporter Polymorphism (5-HTTLPR) With Depression, Perceived Stress, and Norepinephrine in Patients With Coronary Disease: The Heart and Soul Study

“…Details regarding our recruitment procedures have been published previously (23)(24)(25). In brief, we used administrative databases to identify outpatients with documented coronary disease at two Department of Veterans Affairs (VA) medical centers in California (San Francisco VA Medical Center and VA Palo Alto Health Care System), one university medical center (University of California, San Francisco), and nine public health clinics in the Community Health Network of San Francisco.…”

“…Details regarding the analysis of 24-hour urinary norepinephrine excretion have been described elsewhere in greater detail (23). In brief, the participants were instructed to collect all urine for 24 hours between the study appointment and the time when a researcher visited their home the next day and to keep the urine collection jugs refrigerated at all times.…”

Depression and Cardiovascular Disease

“…Alterations in cardiac autonomic tone 16 Common genetic vulnerability 17 Enhanced activity of the hypothalamic pituitary-axis 18 Greater platelet activation 19 Increased catecholamine levels 20 Increased whole blood serotonin 21 Inflammatory processes 22 Lower omega-3 fatty acid levels 23 Mental-stress induced ischemia 24 Toxicity of tricyclic antidepressants 25 Potential behavioral mechanisms Dietary factors 26 Lack of exercise 27 Medication nonadherence 28 Poor social support 29 …”

Prognosis in Heart Failure and the Value of β-Blockers Are Altered by the Use of Antidepressants and Depend on the Type of Antidepressants Used

“…This is noteworthy because depression alone is known to worsen the prognosis in HF. [1][2][3][4][5][6][7][8][9][10][11] Various reasons for this observed increased risk of death in depressed patients with HF have been proposed: nonadherence to HF medication, 12,13 smoking and lack of exercise, 14,15 greater catecholamine levels, 16 increased serotonin and platelet activation, 17 and antidepressant toxicity. 18 -20 Polypharmaceutical treatment in patients with HF has not been studied systematically, and because depression is associated with a poorer prognosis, spontaneous observations of interactions are unlikely.…”