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Original Investigation
June 10, 2020

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

Author Affiliations
  • 1Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, Tavistock Place, London, United Kingdom
  • 2Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
  • 3Department of Molecular and Clinical Medicine, Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Sweden
  • 4Eternal Heart Care Centre & Research Institute, Jaipur, India
  • 5Health Action by People, Trivandrum, India
  • 6Department of Medicine, University of Ottawa, Ontario, Canada
  • 7Faculty of Health Sciences, Simon Fraser University, Burnaby, Division of Cardiology, Providence Health Care, Vancouver, British Columbia, Canada
  • 8Department of Cardiac Sciences, King Fahad Cardiac Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  • 9University of the Philippines College of Medicine, Manila, Philippines
  • 10Masira Research Institute, Medical School, Universidad de Santander (UDES), FOSCAL, Bucaramanga, Colombia
  • 11Department of Medicine, Universidade de Santo Amaro, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
  • 12Universidad de La Frontera, Temuco, Chile
  • 13Istanbul Medeniyet University, Faculty of Medicine, Department of Internal Medicine, Istanbul, Turkey
  • 14Africa Unit for Transdisciplinary Health Research, North-West University, Potchefstroom, South Africa
  • 15Estudios Clínicos Latinoamérica (ECLA), Rosario, Santa Fe, Argentina
  • 16Faculty of Medicine, UiTM, Malaysia
  • 17University of Zimbabwe College of Health Sciences, Department of Physiology, Harare, Zimbabwe
  • 18Department of Medicine, Queen's University, Kingston, Ontario, Canada
  • 19Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
  • 20Department of Medicine, Dubai Medical University, Hatta Hospital, Dubai Health Authority, Dubai, United Arab Emirates
  • 21Department of Angiology, Wroclaw Medical University, Poland
  • 22Advocate Research Institute, Advocate Health Care, Downers Grove, Illinois
  • 23Institute for Community and Public Health, Birzeit University, Birzeit, Palestine
  • 24Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan
  • 25Independent University, Bangladesh, Dhaka, Bangladesh
  • 26National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China
JAMA Psychiatry. Published online June 10, 2020. doi:10.1001/jamapsychiatry.2020.1351
Key Points

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 145 862 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.


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.

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