title: Association between endothelial dysfunction and frailty: the Toledo Study for Healthy Aging.
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. ADMAvalues 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.
authors: Cristina
authors: C
authors: Alonso-Bouzón
authors: Laure
authors: L
authors: Carcaillon
authors: Francisco J
authors: FJ
authors: García-García
authors: María S
authors: MS
authors: Amor-Andrés
authors: Mariam
authors: M
authors: El Assar
authors: Leocadio
authors: L
authors: Rodríguez-Mañas
mesh_terms: D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D050197:Atherosclerosis / Q000150:complications* / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D015897:Comorbidity; D003710:Demography; D005260:Female; D016330:Frail Elderly; D015577:Geriatric Assessment; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D013030:Spain / Q000453:epidemiology
chemical_list: D015415:Biomarkers; C018524:N,N-dimethylarginine; D001120:Arginine
references: J Am Geriatr Soc. 2010 Nov;58(11):2142-8
references: 21054295
references: PLoS One. 2012;7(4):e35739
references: 22558213
references: Arch Intern Med. 2007 Apr 9;167(7):635-41
references: 17420420
references: J Am Coll Cardiol. 2006 Mar 21;47(6):1239-312
references: 16545667
references: J Epidemiol Community Health. 2012 Jul;66(7):e15
references: 21502089
references: J Am Geriatr Soc. 2005 Aug;53(8):1321-30
references: 16078957
references: JAMA. 2006 May 3;295(17):2018-26
references: 16670410
references: J Nutr Health Aging. 2011 Nov;15(9):756-60
references: 22089224
references: Circulation. 2008 Aug 26;118(9):961-7
references: 18697822
references: Autoimmun Rev. 2010 Oct;9(12):830-4
references: 20678595
references: J Am Geriatr Soc. 2006 Nov;54(11):1674-81
references: 17087693
references: Kidney Int. 2001 Apr;59(4):1466-72
references: 11260409
references: Am J Geriatr Cardiol. 2008 Mar-Apr;17(2):101-7
references: 18326951
references: Arterioscler Thromb Vasc Biol. 2003 Aug 1;23(8):1455-9
references: 12805079
references: Vasc Med. 2005 Jul;10 Suppl 1:S11-7
references: 16444864
references: Atherosclerosis. 2013 Jun;228(2):390-9
references: 23587283
references: Atherosclerosis. 2013 Jul;229(1):149-54
references: 23659870
references: J Am Geriatr Soc. 2006 Jun;54(6):991-1001
references: 16776798
references: J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M158-66
references: 11253157
references: Exp Gerontol. 2012 Sep;47(9):734-40
references: 22776133
references: J Gerontol A Biol Sci Med Sci. 2013 Jan;68(1):62-7
references: 22511289
references: Aging Cell. 2009 Jun;8(3):226-38
references: 19245678
references: Diabetes Res Clin Pract. 2012 Apr;96(1):47-52
references: 22189171
references: J Nutr Health Aging. 2011 Dec;15(10):852-6
references: 22159772
references: J Clin Endocrinol Metab. 2012 Aug;97(8):2898-906
references: 22679065
references: J Clin Epidemiol. 1999 Nov;52(11):1015-21
references: 10526994
references: J Gerontol A Biol Sci Med Sci. 2009 Jun;64(6):675-81
references: 19276189
references: Arch Intern Med. 2002 Nov 11;162(20):2333-41
references: 12418947
references: Circulation. 2011 Nov 1;124(18):2020-45
references: 21959305
references: Pharmacol Rep. 2006 Mar-Apr;58(2):159-78
references: 16702618
references: J Am Coll Cardiol. 2005 Aug 2;46(3):518-23
references: 16053968
references: Circulation. 2003 Aug 26;108(8):933-8
references: 12912818
references: Int Immunopharmacol. 2013 Jun;16(2):322-31
references: 23619555
references: Clin Chem Lab Med. 2004;42(12):1377-83
references: 15576299
references: J Gerontol A Biol Sci Med Sci. 2007 Jul;62(7):731-7
references: 17634320
references: Eur J Clin Invest. 2005 Oct;35(10):622-6
references: 16178881
references: Atherosclerosis. 2012 Dec;225(2):504-10
references: 23092827
references: Atherosclerosis. 2011 May;216(1):109-14
references: 21349522
references: Curr Cardiol Rev. 2010 May;6(2):82-90
references: 21532773
references: J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56
references: 11253156
references: Clin Chem. 2007 Feb;53(2):273-83
references: 17185364
references: Vasc Med. 2005 Jul;10 Suppl 1:S73-81
references: 16444872
references: Arch Intern Med. 2006 Feb 27;166(4):418-23
references: 16505261
references: Med Clin (Barc). 2001 Mar 24;116(11):401-7
references: 11333686
references: Circulation. 2003 Apr 15;107(14):1891-5
references: 12681993
references: PLoS One. 2012;7(3):e32401
references: 22403651
references: Hypertension. 2005 Sep;46(3):454-62
references: 16103272
references: J Clin Epidemiol. 1997 May;50(5):541-6
references: 9180646
references: Circulation. 1999 Jun 22;99(24):3092-5
references: 10377069
references: Front Physiol. 2012 May 28;3:132
references: 22783194