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J Am Geriatr Soc. 2019 Jan 17. doi: 10.1111/jgs.15731. [Epub ahead of print]

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

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INSERM U970, Paris Cardiovascular Research Center, Paris Descartes University, Sorbonne Paris Cité, Paris, France.
Service de Médecine et Réadaptation, Hôpitaux de Saint-Maurice, Saint-Maurice, France.
Bordeaux Population Health Research Center, Team HEALTHY, UMR1219, University of Bordeaux, Inserm, Bordeaux, France.
CHU de Bordeaux, Pole de Sante Publique, Service d'Information Medicale, Bordeaux, France.
Inserm, U1061, La Colombière Hospital, Montpellier, France.
Inserm, U1061, University of Montpellier, Montpellier, France.



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.


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.


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.


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 00:1-7, 2019.


cardiovascular events; depressive symptoms; elderly individuals; longitudinal study; mortality


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