Poor health behaviors largely explain link between depression and cardiovascular events

Objective, To understand the association between depressive symptoms and increased risk of cardiovascular events. Design. Prospective cohort study Setting and participants. A total of 1024 patients with stable coronary heart disease were recruited between September 2000 and December 2002 from 12 outpatient Veterans Affairs, university, and public health clinics in the San Francisco Bay area and were followed through January 2008. Patients were eligible for enrollment if they had a history of myocardial infarction, prior exercise-induced ischemia on an exercise or pharmacologic stress test, ≥ 50% stenosis in ≥ 1 coronary vessels, history of coronary revascularization, or diagnosis of coronary artery disease documented by an internist or cardiologist. Of the initial participants who completed the baseline examination, 7 could not be reached for follow-up, leaving 1017 for evaluation. Participants completed the intake examination, fasting blood draw, psychiatric interview, depression questionnaire, echocardiogram, 24-hour ambulatory electrocardiogram, and 24-hour urine collection. Main outcome measures. Proportional hazards models were used to evaluate the extent to which baseline cardiovascular disease (CVD) and biologic and behavioral mediators explained the association between depressive symptoms and cardiovascular outcome events. Depressive symptoms were assessed with the 9-item Patient Health Questionnaire (PHQ) and the Computerized Diagnostic Interview Schedule for DSM-IV. Cardiovascular events were defined as heart failure hospitalizations, nonfatal myocardial infarctions, stroke, transient ischemic attacks, or death. Main results. Overall, a total of 341 cardiovascular events occurred over 4876 person-years of follow-up. Mean follow-up was 4.8 years. Of the 1017 patients, 199 (19.6%) had depressive symptoms as determined by PHQ scores ≥ 10. The age-adjusted annual rate of cardiovascular events was 10% in patients with depressive symptoms compared with 6.7% in those without depressive symptoms (hazard ratio [HR], 1.50 [95% confidence interval {CI}, 1.16-1.95]; P = 0.002). Patients with depressive symptoms were more likely to be female, younger, smokers, less physically active, less adherent to medications, have a higher body mass index, have more comorbidities, use more antidepressants, and have greater urinary norepinephrine excretion, higher C-reactive protein (CRP) levels, and lower omega-3 fatty acid levels. After adjusting for CVD severity and other comorbid conditions, depressive symptoms were still associated with a 31% higher rate of cardiovascular events (HR, 1.31 [95% CI, 1.00-1.71]; P = 0.04). Further adjustment for CRP somewhat attenuated this relationship (HR, 1.24 [95% CI, 0.94-1.63]; P = 0.12), and subsequent adjustment for smoking, medication nonadherence, and physical inactivity completely eliminated the relationship between depressive symptoms and cardiovascular events (HR, 1.05 [95% CI, 0.79-1.40]; P = 0.75). In the final overall model, physical inactivity was associated with a 44% higher rate of cardiovascular events (HR, 1.44 [95% CI, 1.14-1.82]; P = 0.002), adjusting for depressive symptoms, age, disease severity, comorbid conditions, CRP, smoking, and medication adherence. Conclusion. In patients with stable coronary heart disease, those with depressive symptoms at baseline had a 50% greater rate of subsequent cardiovascular events. Health-related behaviors, such as physical inactivity, explained much of the association between depressive symptoms and future cardiovascular events.