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

Abstract

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 145 862 participants, 61 235 (58%) were male and the mean (SD) age was 50.05 (9.7) years. Of those, 15 983 (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.

Figure 1.. Associations Between Number of Depressive Symptoms and Primary Outcomes

Relative risks of incident cardiovascular disease (CVD), mortality, and the combined outcome (the first of either incident CVD or death) increased with the number of symptoms of depression. Participants who were either asymptomatic or only reported feeling sad, blue, or depressed received a Short-Form Composite International Diagnostic Interview (CIDI-SF) score of 0. We report hazard ratios (HRs) for each CIDI-SF score from 1 to 7 relative to those with a score of 0, using Cox proportional hazards models adjusted for age, sex, educational attainment, urban/rural residence, use of statins, 1 or 2 or more disabilities, former and current smoking and alcohol use, hypertension, diabetes, social isolation (an index from 0-5), and including random intercepts for study center (model 2). P for trend was modeled using the CIDI-SF score as a continuous variable.

Figure 2.. Associations Between ≥4 Symptoms of Depression and Mortality and Incident CVD, in Subgroups Determined by Traditional NCD Risk Factors and Social Determinants of Health

Associations between depression and incident cardiovascular death (CVD), mortality, and the combined outcome (the first of either incident CVD or death) were stronger in men compared with women but were otherwise independent of traditional risk factors after adjustments for age, sex, educational attainment, urban/rural residence, use of statins, 1 or 2 or more disabilities, current smoking, alcohol use, hypertension, diabetes, and social isolation index and including random intercepts for center (model 2). HR indicates hazard ratio; NCD, noncommunicable diseases; WHR, waist-to-hip ratio.