Association of tumor necrosis factor-related apoptosis-inducing ligand with total and cardiovascular mortality in older adults.
OBJECTIVE
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits biological activity on vascular cells in vitro. Rapid variation of circulating TRAIL levels occurs during acute coronary ischemia, suggesting that biological pathways involving TRAIL may be activated during ischemic heart disease. However, whether differential levels of soluble TRAIL in normal individuals are associated with adverse health outcomes has not been investigated. We tested the hypothesis that TRAIL levels predict mortality in a population based sample of community dwelling men and women.


METHODS
Plasma TRAIL level was measured by ELISA at baseline in 1282 adults (mean age 68 years) enrolled in the InCHIANTI study. Vital status was ascertained over the six-year follow-up.


RESULTS
In multivariable Cox regression analysis adjusted for potential confounders including prevalent cardiovascular diseases (CVD), ankle-brachial index, electrocardiogram abnormalities, and inflammatory markers, baseline TRAIL levels were inversely related to all-cause mortality (p=0.008). In stratified analyses, the prognostic effect of TRAIL level was strong and highly significant in participants with prevalent CVD (N=321), (lowest versus highest quartile: HR 3.1; 95% CI 1.5-6.5) while it was negligible in those free of CVD (p value for the interaction term between CVD status and TRAIL levels=0.038). Similar findings were obtained when CVD mortality was considered as the outcome of interest.


CONCLUSIONS
In older patients with CVD, low levels of TRAIL were associated with increased risk of death over a period of 6 years. Lower concentration of circulating TRAIL may be related to the clinical evolution of older adults with CVD.
Department of Clinical and Experimental Medicine, Section of Internal Medicine, Gerontology and Geriatrics, University of Ferrara, Via Savonarola, 9, I-44100 Ferrara, Italy. vlt@unife.it
Stefano
S
Volpato
Luigi
L
Ferrucci
Paola
P
Secchiero
Federica
F
Corallini
Giovanni
G
Zuliani
Renato
R
Fellin
Jack M
JM
Guralnik
Stefania
S
Bandinelli
Giorgio
G
Zauli
D000328:Adult; D000368:Aged; D055109:Ankle Brachial Index; D002318:Cardiovascular Diseases / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood*
D053221:TNF-Related Apoptosis-Inducing Ligand