Comorbid depression and anxiety symptoms as predictors of cardiovascular events: results from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) study.

Among psychiatric symptoms linked to cardiovascular disease (CVD), anxiety and depression are perhaps the most common. Both conditions are widespread among cardiac patients (1-3), each is associated with behavioral and pathophysiological markers of CVD risk (4-7), and the independence of anxiety and depression as predictors of CVD outcomes is supported by multiple studies (8-15). Anxiety and depressive disorders also share treatment approaches, with serotonin reuptake inhibitor medications, cognitive behavioral therapy, and their combination recognized as effective interventions for both conditions (16). The high degree of overlap between anxiety and depression symptoms with regard to their co-morbidity in clinical populations, effective methods of treatment, and specific symptoms may represent more than coincidence. Some have suggested that anxiety and depression may be characteristics of a broader negative affect dimension (17-18). Others have argued that they are produced by the same dysfunctional biology or that they may originate from parallel genetic dispositions (19-21). Despite the strong convergence between these two psychiatric conditions and evidence of their independent value in predicting CVD risk, few studies have investigated the combined or interactive contribution of anxiety and depression in the prediction of CVD events (22-23). If anxiety and depression are indeed variations of a similar biopsychosocial origin, then either of two outcomes could follow: 1) These conditions could interchangeably predict CVD events, and the presence of both would not be more predictive than either alone; or 2) The co-occurrence of anxiety and depression could predict CVD risk above and beyond their independent predictions. The literature provides differing views regarding these hypotheses. For one, depression is a more established predictor of cardiovascular outcomes than anxiety (13-14), the latter boasting a smaller and less consistent empirical literature to date (17). This observation appears to argue against treating the conditions interchangeably in regards to CVD risk, but comes with the limitation that much of the previous anxiety-CVD research has focused on men (e.g., 24). In contrast, recent findings drawn from large female cohorts such as the Nurse's Health Study (25) and Women's Health Initiative (26) have supported relationships between anxiety symptom severity and/or anxiety disorders with adverse cardiac events. Two prospective studies to date have directly compared anxiety and depression alone versus jointly in predicting CVD outcomes (22-23). These studies produced evidence of independent statistical relationships between anxiety and depressive disorders with adverse cardiac events (22), and between questionnaire measures of phobic anxiety and depression and ventricular arrhythmias (23), respectively. Whereas Frasure-Smith (22) reported no added predictive effects of combining anxiety and depression status, Watkins and colleagues (23) also described the largest associations with ventricular arrhythmias as resulting from a composite of anxiety and depression scores. The fact that women comprised less than 30% of the sample in both studies could be important given the higher rates of anxiety and depressive disorders diagnosed in women relative to men (27). This study describes relationships among anxiety, depression, and CVD mortality and events in a sample of women undergoing coronary angiography as part of an evaluation for suspected myocardial ischemia. We were able to expand upon previous research in this area using a large female cohort, followed for a median of nearly 6-years, in which we were able to directly control for CAD severity with the use of quantitative angiograms. Using questionnaire-measured severity of trait anxiety and depression symptoms, we specifically compared independent versus interactive prediction models.