• Open Access

Identification of a metabolic signature for multidimensional impairment and mortality risk in hospitalized older patients

Authors

  • Luigi Fontana,

    1. Department of Medicine, Salerno University Medical School, Salerno, Italy
    2. Division of Geriatrics and Nutritional Science, Washington University in St.Louis, St.Louis, MO, USA
    3. CEINGE Biotecnologie Avanzate, Napoli, Italy
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  • Filomena Addante,

    1. Department of Medical Sciences, Gerontology-Geriatric Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
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  • Massimiliano Copetti,

    1. Unit of Biostatistics, IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy
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  • Giulia Paroni,

    1. Department of Medical Sciences, Gerontology-Geriatric Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
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  • Andrea Fontana,

    1. Unit of Biostatistics, IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy
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  • Daniele Sancarlo,

    1. Department of Medical Sciences, Gerontology-Geriatric Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
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  • Fabio Pellegrini,

    1. Unit of Biostatistics, IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Italy
    2. Unit of Biostatistics, DCPE, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy
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  • Luigi Ferrucci,

    Corresponding author
    1. National Institute on Aging, Longitudinal Studies Section, Harbor Hospital Center, Baltimore, MD, USA
    • Department of Medicine, Salerno University Medical School, Salerno, Italy
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  • Alberto Pilotto

    Corresponding author
    1. Department of Medical Sciences, Gerontology-Geriatric Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
    2. Geriatrics Unit, Azienda ULSS 16 Padova, S Antonio Hospital, Padova, Italy
    • Department of Medicine, Salerno University Medical School, Salerno, Italy
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Correspondence

Luigi Fontana, Division of Geriatrics and Nutritional Science, Washington University, School of Medicine, 4566 Scott Avenue, Campus Box 8113, St. Louis, MO 63110, USA. Tel.: +1 314 362 3506; fax: +1 314 362 7657; e-mail: lfontana@dom.wustl.edu;

Alberto Pilotto, Geriatrics Unit, Azienda ULSS 16 Padova, Saint Antonio Hospital, Via Facciolati 71, 35127 Padova, Italy. Tel./fax: (+39) 049 8215300; email: alberto.pilotto@sanita.padova.it

Summary

A combination of several metabolic and hormonal adaptations has been proposed to control aging. Little is known regarding the effects of multiple deregulations of these metabolic and hormonal systems in modulating frailty and mortality in hospitalized elderly patients. We measured 17 biological serum parameters from different metabolic/hormonal pathways in 594 hospitalized elderly patients followed up to 1 year who were stratified into three groups according to their multidimensional impairment, evaluated by a Comprehensive Geriatric Assessment (CGA)-based Multidimensional Prognostic Index (MPI). The mortality incidence rates were 7% at 1 month and 21% at 1 year. Our data show that frailty and mortality rate were positively associated with chronic inflammation and with a down-regulation of multiple endocrine factors. Of the 17 biomarkers examined, blood levels of IGF-1, triiodothyronine, C-reactive protein, erythrocyte sedimentation rate, white blood cell and lymphocyte counts, iron, albumin, total cholesterol, and LDL-c were significantly associated with both MPI severity grade and mortality. In multivariate Cox proportional hazard model, the following biomarkers most strongly predicted the risk of mortality (adjusted hazard ratio (HR) per 1 quintile increment in predictor distribution): IGF-1 HR = 0.71 (95% CI: 0.63–0.80), CRP HR = 1.48 (95% CI: 1.32–1.65), hemoglobin HR = 0.82 (95% CI: 0.73–0.92), and glucose HR = 1.17 (95% CI: 1.04–1.30). Multidimensional impairment assessed by MPI is associated with a distinctive metabolic ‘signature’. The concomitant elevation of markers of inflammation, associated with a simultaneous reduction in multiple metabolic and hormonal factors, predicts mortality in hospitalized elderly patients.

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