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Background: Vital exhaustion, a psychological measure characterized by fatigue and depressive symptoms, has been suggested to be an independent risk factor for ischaemic heart disease (IHD) but the generality of the phenomenon remains in question. The aim of this study is to describe prevalence of these symptoms in a community sample and determine whether they prospectively predict increased risk of IHD and all-cause mortality in men and women., Methods: The study base was 4084 men and 5479 women aged 20-98 free of IHD examined in 1991-1993 in the Copenhagen City Heart Study. Events were ascertained through record linkage until 1998 for IHD and September 2000 for all-cause mortality. There were 483 first hospital admissions and deaths caused by IHD and 1559 deaths from all causes during follow-up., Results: The 17 items on the vital exhaustion questionnaire were frequently endorsed with prevalence ranging from 6 to 47 per cent, higher in women. All but 4 of the 17 items were significantly associated with IHD with significant relative risks (RR) ranging between 1.36 (95% CI: 1.08, 1.72) and 2.10 (95% CI: 1.63, 2.71). Associations with all-cause mortality were also observed, but were weaker. RR of both IHD and all-cause mortality increased with increasing item sum score and were similar in men and women. For IHD, RR reached a maximum of 2.57 (95% CI: 1.65, 4.00) for subjects endorsing >9 items. The similar RR for all-cause mortality was 2.50 (95% CI: 2.09, 2.99). Multivariate adjustment for biological, behavioural, and socioeconomic risk factors did not substantially affect the association for IHD but attenuated the association with all-cause mortality., Conclusions: Measures of fatigue and depression were common symptoms in this population sample and convey increased risk of IHD and of all-cause mortality. We propose this knowledge begin to be implemented in risk assessment in clinical practice.