Association of Symptoms of Depression With Cardiovascular Disease and Mortality in Low-, Middle-, and High-Income Countries

This cohort study identifies associations between depressive symptoms and incident cardiovascular disease and all-cause mortality in countries at different levels of economic development and in urban and rural areas Importance Depression is associated with incidence of and premature death from cardiovascular disease (CVD) and cancer in high-income countries, but it is not known whether this is true in low- and middle-income countries and in urban areas, where most people with depression now live. Objective To identify any associations between depressive symptoms and incident CVD and all-cause mortality in countries at different levels of economic development and in urban and rural areas. Design, Setting, and Participants This multicenter, population-based cohort study was conducted between January 2005 and June 2019 (median follow-up, 9.3 years) and included 370 urban and 314 rural communities from 21 economically diverse countries on 5 continents. Eligible participants aged 35 to 70 years were enrolled. Analysis began February 2018 and ended September 2019. Exposures Four or more self-reported depressive symptoms from the Short-Form Composite International Diagnostic Interview. Main Outcomes and Measures Incident CVD, all-cause mortality, and a combined measure of either incident CVD or all-cause mortality. Results Of 145862 participants, 61235 (58%) were male and the mean (SD) age was 50.05 (9.7) years. Of those, 15983 (11%) reported 4 or more depressive symptoms at baseline. Depression was associated with incident CVD (hazard ratio [HR], 1.14; 95% CI, 1.05-1.24), all-cause mortality (HR, 1.17; 95% CI, 1.11-1.25), the combined CVD/mortality outcome (HR, 1.18; 95% CI, 1.11-1.24), myocardial infarction (HR, 1.23; 95% CI, 1.10-1.37), and noncardiovascular death (HR, 1.21; 95% CI, 1.13-1.31) in multivariable models. The risk of the combined outcome increased progressively with number of symptoms, being highest in those with 7 symptoms (HR, 1.24; 95% CI, 1.12-1.37) and lowest with 1 symptom (HR, 1.05; 95% CI, 0.92 -1.19; P for trend < .001). The associations between having 4 or more depressive symptoms and the combined outcome were similar in 7 different geographical regions and in countries at all economic levels but were stronger in urban (HR, 1.23; 95% CI, 1.13-1.34) compared with rural (HR, 1.10; 95% CI, 1.02-1.19) communities (P for interaction = .001) and in men (HR, 1.27; 95% CI, 1.13-1.38) compared with women (HR, 1.14; 95% CI, 1.06-1.23; P for interaction < .001). Conclusions and Relevance In this large, population-based cohort study, adults with depressive symptoms were associated with having increased risk of incident CVD and mortality in economically diverse settings, especially in urban areas. Improving understanding and awareness of these physical health risks should be prioritized as part of a comprehensive strategy to reduce the burden of noncommunicable diseases worldwide. Question Does the increased risk of incident cardiovascular disease and mortality in middle-aged adults with depressive symptoms vary across and within countries? Findings In this cohort study from 21 countries and 145862 participants, cardiovascular events and death increased by 20% in people with 4 or more depressive symptoms compared with people without. The relative risk increased in countries at all economic levels but was more than twice as high in urban than rural areas. Meaning Adults with depressive symptoms experience poor physical health outcomes and increased risk of mortality across the world and in different settings, especially in urban areas.