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Effects of depressive symptoms and coronary heart disease and their interactive associations on mortality in middle-aged adults: the Whitehall II cohort study
  1. Hermann Nabi1,2,
  2. Martin J Shipley3,
  3. Jussi Vahtera4,5,
  4. Martica Hall6,
  5. Jyrki Korkeila7,
  6. Michael G Marmot3,
  7. Mika Kivimäki3,5,
  8. Archana Singh-Manoux1,2,3,8
  1. 1INSERM, U1018, Centre for Research in Epidemiology and Population Health, Epidemiology of Occupational and Social Determinants of Health, France
  2. 2University of Versailles, St Quentin, UMRS 1018, France
  3. 3Department of Epidemiology and Public Health, University College London, UK
  4. 4Department of Public Health, University of Turku and Turku University Hospital, Finland
  5. 5Finnish Institute of Occupational Health, Helsinki, Finland
  6. 6Department of Psychiatry, University of Pittsburgh School of Medicine, Pennsylvania, USA
  7. 7Department of Psychiatry, University of Turku and Harjavalta Hospital, Satakunta Hospital District, Finland
  8. 8Hôpital Ste Périne, AP-HP, Centre de Gérontologie, Paris, France
  1. Correspondence to Dr Hermann Nabi, Centre for Research in Epidemiology and Population Health /U1018, Hôpital, Paul Brousse, Bâtiment 15/16, 16 avenue Paul Vaillant Couturier 94807 Villejuif Cedex, France; hermann.nabi{at}


Background Depression and mortality have been studied separately in patients with coronary heart disease (CHD) and in populations healthy at study inception. This does not allow comparisons across risk-factor groups based on the cross-classification of depression and CHD status.

Objective To examine effects of depressive symptoms and CHD and their interactive associations on mortality in middle-aged adults followed over 5.6 years.

Design and setting A prospective population-based cohort study of 5936 middle-aged men and women from the British Whitehall II study. We created four risk-factor groups based on the cross-classification of depressive symptoms and CHD status.

Results The age-adjusted and sex-adjusted hazard ratios for death from all causes were 1.67 (p<0.05) for participants with only CHD, 2.10 (p<0.001) for those with only depressive symptoms and 4.99 (p<0.001) for those with both CHD and depressive symptoms when compared to participants without either condition. The two latter risk-factor groups remained at increased risk after adjustments for relevant confounders. The relative excess risk due to the interaction between depressive symptoms and CHD for all-cause mortality was 3.58 (95% CI −0.09 to 7.26), showing some evidence of an additive interaction. A similar pattern was also observed for cardiovascular death.

Conclusions This study provides evidence that depressive symptoms are associated with an increased risk of all-cause and cardiovascular death and that this risk is particularly marked in depressive participants with co-morbid CHD.

  • Coronary heart disease
  • depressive symptoms, survival, depression, epidemiology

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  • Funding The Whitehall II study is supported by grants from the Medical Research Council; British Heart Foundation; Health and Safety Executive; Department of Health; National Heart Lung and Blood Institute (R01HL036310), US, NIH: National Institute on Ageing (R01AG013196 and R01AG034454), US, NIH; Agency for Health Care Policy Research (HS06516); and the John D and Catherine T MacArthur Foundation Research Networks on Successful Midlife Development and Socio-economic Status and Health. MK and JV are supported by the Academy of Finland (projects 124271, 124322, 129262 and 132944) and EU New OSH ERA Programme and MK is additionally supported by the BUPA Foundation, UK, the National Heart, Lung, and Blood Institute and the National Institute on Aging, USA. MJS is supported by a grant from the British Heart Foundation. AS-M is supported by a “European Young Investigator Award” from the European Science Foundation.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethical approval for the Whitehall II study was obtained from the University College London Medical School committee on the ethics of human research, and written informed consent was obtained from each participant.

  • Provenance and peer review Not commissioned; externally peer reviewed.