Depression and cardiac surgery

Abstract: Cardiovascular disease and depression are likely to be two of the three leading causes of global burden of disease. Depression is common in patients with coronary artery disease and is independently associated with increased cardiovascular morbidity and mortality. The incidence of major depressive disorder is two to three times higher in patients with cardiovascular disease than in the general population. In patients with coronary artery disease, clinically significant depression is prevalent in 31% to 45% of patients. Moderate to severe depression before coronary artery bypass grafting (CABG) is an indicator of worse long-term survival. The overall aim of this thesis was to study the association between depression and cardiovascular morbidity and mortality in patients undergoing cardiac surgery by epidemiological methods and cross-linking of national Swedish registers. Study I investigated the association between preoperative antidepressant use and long- term survival following primary isolated CABG. Of 10884 patients 11% were using antidepressants before surgery. After multivariable adjustment, antidepressant use was associated with increased mortality hazard ratio (HR) 1.45; 95% confidence interval (CI) 1.18–1.77, compared with non-use of antidepressants. Antidepressant use was also associated with an increased risk of rehospitalization (HR1.40; 95% CI 1.19–1.65) and the composite endpoint rehospitalization or death (HR 1.44; 95% CI 1.26–1.65). Study II We hypothesized that depressed patients would have lower use of guideline- directed medical therapy for secondary prevention of cardiovascular events following CABG. We included all 10586 patients who underwent primary isolated CABG in Sweden between 2006 and 2008. During the first year after CABG, 93% of all patients had at least two dispensed prescriptions for an antiplatelet agent, 68% for an ACEI/ARB, 91% for a beta-blocker, and 92% for a statin. 57% had prescriptions for all four medication classes. After four years (n=4034), 44% had filled prescriptions for all four medication classes. Preoperative depression was not significantly associated with a lower use of all four medication classes. Study III investigated major depression in 56064 patients who underwent primary, isolated, non-emergent CABG. During a mean follow-up of 7.5 years, 114 patients (35%) with depression died, compared with 13767 patients (25%) in the control group. Depression was significantly associated with increased mortality and the combined end point of death or rehospitalization for MI, heart failure, or stroke (multivariable- adjusted HR 1.65 95% CI 1.37 to 1.99 and 1.61, 1.38 to 1.89, respectively). Study IV investigated if socioeconomic factors modified the association between preoperative depression and survival following CABG. Antidepressant use was a proxy for depression. During a mean follow-up of 4.1 years, 11% patients died in the antidepressant group and 9.7% patients died in the control group. The adjusted risk for death was higher in patients with preoperative antidepressant use (HR 1.27; 95% CI 1.13–1.43), and was practically unchanged after the addition of educational level, family disposable income, and civil status (HR 1.25; 95% CI 1.11–1.41). Study V was a systematic review and meta-analysis performed to provide a summary estimate of the association between preoperative depression and long-term survival after CABG. Seven studies were included with a combined study population of 89490 patients (4002 depressed/85488 non-depressed). All studies observed a positive association between preoperative depression and all-cause mortality, and in 4 studies the association was statistically significant. Patients with depression had a pooled HR of 1.46 (95% CI: 1.23-1.73, p<0.001) for all-cause mortality with moderate heterogeneity (I2 = 50.1% p=0.061). In conclusion depression is a significant, independent risk factor, in patients with cardiovascular disease and should be considered as important as other well-known risk factors like for example heart failure and chronic kidney disease in patients undergoing CABG.