Depression and cardiovascular morbidity and mortality: cause or consequence?

Background: Depression after myocardial infarction has been associated with increased cardiovascular mortality. This study assessed whether depressive symptoms were associated with adverse outcomes in people with a history of an acute coronary syndrome, and evaluated possible explanations for such an association.
Methods and Results: Depressive symptoms were assessed using the General Health Questionnaire at least 5 months after hospital admission for acute myocardial infarction or unstable angina in 1130 participants of the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study, a multicentre, placebo-controlled, clinical trial of cholesterol-lowering treatment. Cardiovascular symptoms, self-rated general health, cardiovascular risk factors, employment status, social support and life events were also assessed at the baseline visit. Cardiovascular death (n=114), non-fatal myocardial infarction (n=108), non-fatal stroke (n=53) and unstable angina (n=274) were documented during a median follow-up period of 8.1 years. Individuals with depressive symptoms (General Health Questionnaire score >/=5; 22% of participants) were more likely to report angina, dyspnoea, claudication, poorer general health, not being in paid employment, few social contacts and/or adverse life events (P<0.05 for all). There was a modest association between depressive symptoms and cardiovascular events (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.13-1.77), but not cardiovascular death (HR 1.12. 95% CI 0.71-1.77). After adjustment for symptoms related to cardiovascular disease, the HR for cardiovascular events was 1.22 (95% CI 0.97-1.53). After further adjustment for employment status, social support and life events, the HR was 1.13 (95% confidence interval 0.87-1.47).
Conclusions: There was no significant association between depressive symptoms and fatal or non-fatal cardiovascular events after adjustment for cardiovascular symptoms associated with poorer prognosis. Previously observed associations between depression and cardiovascular mortality may not be causal.