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Association between endothelial dysfunction and frailty: the Toledo Study for Healthy Aging

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Abstract

Cardiovascular disease (CVD), both clinical and subclinical, has been proposed as one of the mechanisms underlying frailty. However, there is no evidence addressing the relationship between the earliest stage of CVD (endothelial dysfunction) and frailty. The goal of the study was to analyze the association between endothelial dysfunction, evaluated by asymmetric dimethylarginine (ADMA) levels, and frailty. We used data from the Toledo Study for Healthy Aging, a prospective Spanish cohort study. Biological samples were obtained and ADMA levels were determined using an enzyme immunoassay method. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals of frailty associated with ADMA. Adjustments were made for age, gender, cardiovascular risk factors, and presence of atherosclerotic disease (assessed by ankle–brachial index; ABI). One thousand two hundred eighty-seven community-dwelling elderly were included. One hundred seven (8.3 %) were identified as frail, 542 (42.1 %) as pre-frail, and 638 (49.6 %) as non-frail. ADMA values were higher in frail subjects than in non-frail ones. In addition, an interaction between the presence of atherosclerotic disease and ADMA on the odds of frailty (p = 0.045) was detected. After adjustments for age, classical cardiovascular risk factors, and ABI, the risk of frailty was associated with increasing levels of ADMA in subjects without atherosclerotic disease [OR for 1 standard deviation increase in ADMA = 1.14 (1.01–1.28), p = 0.032] but not in those with atherosclerotic disease. In our study, endothelial dysfunction, assessed by ADMA levels, is associated with frailty. These findings provide additional support for a relevant role of vascular system since its earliest stage in frailty.

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Acknowledgments

This work was supported by grants from Ministerio de Economía y Competitividad [Instituto de Salud Carlos III, PI08/1649, PI11/01068, RETICEF RD06/0013], Spanish Government.

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Authors and Affiliations

  1. Geriatric Department, Hospital Universitario de Getafe, Carretera de Toledo, Km, 12.500, 28905, Getafe, Madrid, Spain

    Cristina Alonso-Bouzón & Leocadio Rodríguez-Mañas

  2. Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, Hormones and Cardiovascular Disease Team, 94807, Villejuif, France

    Laure Carcaillon

  3. Geriatric Department, Hospital Virgen del Valle, Complejo Hospitalario de Toledo, Toledo, Spain

    Francisco J. García-García & María S. Amor-Andrés

  4. Fundación para la Investigación Biomédica del Hospital Universitario de Getafe, Madrid, Spain

    Mariam El Assar

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  1. Cristina Alonso-Bouzón
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  2. Laure Carcaillon
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  3. Francisco J. García-García
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  5. Mariam El Assar
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  6. Leocadio Rodríguez-Mañas
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Correspondence to Leocadio Rodríguez-Mañas.

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Alonso-Bouzón, C., Carcaillon, L., García-García, F.J. et al. Association between endothelial dysfunction and frailty: the Toledo Study for Healthy Aging. AGE 36, 495–505 (2014). https://doi.org/10.1007/s11357-013-9576-1

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