Depression Increases the Risk of Death Independently From Vascular Events in Elderly Individuals: The Three-City Study

J Am Geriatr Soc. 2019 Mar;67(3):546-552. doi: 10.1111/jgs.15731. Epub 2019 Jan 17.


Background: How much the association between depressive symptoms (DSs) and all-cause mortality depends on cardiovascular disease (CVD) events is poorly known. We aimed to prospectively quantify the association between DSs at repeated study visits and all-cause and cause-specific mortality, and the influence of incident CVD on this association.

Methods: The Three-City Study has included adults 65 years and older, who were examined at baseline between 1999 and 2001 and after 2, 4, 7, and 10 years of follow-up. At each visit, a score of 16 or greater on the 20-item Center for Epidemiologic Studies Depression Scale defined the presence of DSs. DS status and incident coronary heart disease or stroke events were used as time-dependent variables in a Cox proportional hazard model of mortality.

Results: We studied 7377 participants (63.7% females) aged 73.8 years (SD = 5.4 years) without a history of CVD at baseline examination. DSs were present in 19% to 22% of subjects at each study visit. During a median follow-up of 9.4 years, 650 subjects developed a first CVD, and 1255 had died. After adjustment for baseline sociodemographic variables, vascular risk factors, impairment in daily life activities, and antidepressants, time-dependent DSs were associated with a 28% increased risk of mortality (hazard ratio [HR] = 1.28; 95% confidence interval [CI] = 1.06-1.55), and incident CVD event was associated with a 63% increased risk (HR = 1.63; 95% CI = 1.30-2.04). However, the association between DSs and mortality was not influenced by the occurrence of CVD (HR for DS and CVD interaction = 1.03; 95% CI = 0.66-1.61). A mediation analysis confirmed that incident CVD only explained 6.9% of the excess of mortality associated with DSs.

Conclusion: In older participants, the increased risk of all-cause mortality associated with the presence of DSs at baseline and during follow-up is not modified by and is moderately mediated by incident CVD. J Am Geriatr Soc 67:546-552, 2019.

Keywords: cardiovascular events; depressive symptoms; elderly individuals; longitudinal study; mortality.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living*
  • Aged
  • Antidepressive Agents / therapeutic use*
  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / mortality
  • Cardiovascular Diseases* / psychology
  • Depression* / diagnosis
  • Depression* / drug therapy
  • Depression* / epidemiology
  • Depression* / physiopathology
  • Female
  • Follow-Up Studies
  • France / epidemiology
  • Humans
  • Incidence
  • Longitudinal Studies
  • Male
  • Mortality
  • Proportional Hazards Models
  • Risk Factors
  • Socioeconomic Factors


  • Antidepressive Agents