Increased levels of soluble Receptor for Advanced Glycation End-Products (RAGE) are associated with a higher risk of mortality in frail older adults

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Author
Butcher, Lee
Carnicero, Jose
Gomez-Cabrero, David
Dartigues, Jean-Francois
Peres, Karine
Garcia-Garcia, Francisco Jose
Rodriguez-Mañas, Leocadio
Erusalimsky, Jorge
Date
2019-06-18Acceptance date
2019-05-24
Date Accepted
2019-05-29
Type
Article
acceptedVersion
Publisher
Oxford University Press
ISSN
1468-2834
Metadata
Show full item recordAbstract
Objective: To evaluate the relationship between serum levels of the soluble
Receptor for Advanced Glycation End-products (sRAGE) and mortality in frail and
non-frail older adults.
Methods: We studied 691 subjects (141 frail and 550 non-frail) with a median age of
75 years from two population-based cohorts, the Toledo Study of Healthy Aging and
the AMI study, who were enrolled to the FRAILOMIC initiative. Multivariate Cox
proportional hazards regression and Kaplan-Meier survival analysis were used to
assess the relationship between baseline sRAGE and mortality.
Results: During 6 years of follow-up 101 participants died (50 frail and 51 non-frail).
Frail individuals who died had significantly higher sRAGE levels than those who
survived (median [IQR]: 1563 [1015-2248] vs 1184 [870-1657] pg/mL, P=0.006),
whilst no differences were observed in the non-frail group (1262 [1056-1554] vs 1186
[919-1551] pg/mL, P=0.19). Among frail individuals higher sRAGE levels were
associated with an increased risk of death after adjustment for relevant covariates
(HR=2.72 per unit increment in ln-sRAGE, 95%CI 1.48-4.99, P=0.001). In contrast,
in non-frail individuals sRAGE showed no association with mortality. Survival curves
demonstrated that among frail individuals the incidence of death was significantly
higher in the top sRAGE quartile compared to the three lower quartiles (P=0.002).
Area under the ROC curve analysis demonstrated that for frail individuals, inclusion
of sRAGE in the hazard model increased its predictive accuracy by ~3%.
Conclusions: sRAGE is an independent predictor of mortality among frail
individuals. Determination of sRAGE in frail subjects could be useful for prognostic
assessment and treatment stratification.
Journal/conference proceeding
Age and Ageing;
Description
Article published in Age and Ageing on 18 June 2019, available at: https://doi.org/10.1093/ageing/afz073.
Sponsorship
Cardiff Metropolitan University (Grant ID: Cardiff Metropolian (Internal))
The FRAILOMIC study was supported by the European Union Seventh Framework Programme under grant agreement number 305483.
The AMI project was funded by AGRICA (CAMARCA, CRCCA, CCPMA PREVOYANCE, CPCEA, AGRI PREVOYANCE), la Mutualité Sociale Agricole (MSA) de Gironde, la Caisse Centrale de la Mutualité Sociale Agricole (CCMSA).
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