Context: The stress hormone cortisol has been linked with unfavorable cardiovascular risk factors, but longitudinal studies examining whether high levels of cortisol predict cardiovascular mortality are largely absent.

Objective: The aim of this study was to examine whether urinary cortisol levels predict all-cause and cardiovascular mortality over 6 yr of follow-up in a general population of older persons.

Design and Setting: Participants were part of the InCHIANTI study, a prospective cohort study in the older general population with 6 yr of follow-up.

Participants: We studied 861 participants aged 65 yr and older.

Main Outcome Measure: Twenty-four-hour urinary cortisol levels were assessed at baseline. In the following 6 yr, all-cause and cardiovascular mortality was ascertained from death certificates. Cardiovascular mortality included deaths due to ischemic heart disease and cerebrovascular disease.

Results: During a mean follow-up of 5.7 (sd = 1.2) yr, 183 persons died, of whom 41 died from cardiovascular disease. After adjustment for sociodemographics, health indicators, and baseline cardiovascular disease, urinary cortisol did not increase the risk of noncardiovascular mortality, but it did increase cardiovascular mortality risk. Persons in the highest tertile of urinary cortisol had a five times increased risk of dying of cardiovascular disease (hazard ratio = 5.00; 95% confidence interval = 2.02–12.37). This effect was found to be consistent across persons with and without cardiovascular disease at baseline (p interaction = 0.78).

Conclusions: High cortisol levels strongly predict cardiovascular death among persons both with and without preexisting cardiovascular disease. The specific link with cardiovascular mortality, and not other causes of mortality, suggests that high cortisol levels might be particularly damaging to the cardiovascular system.