title: Aging and the burden of multimorbidity: associations with inflammatory and anabolic hormonal biomarkers.
abstract: BACKGROUND
  Multimorbidity increases with aging, but risk factors beyond age are unknown.
  
  
  OBJECTIVE
  To investigate the association of inflammatory and anabolic hormonal biomarkers with presence and prospective development of multimorbidity.
  
  
  METHODS
  Nine-year longitudinal study of 1018 participants aged 60 years or older (InCHIANTI Study). Multimorbidity was evaluated at baseline and follow-up visits as number of diagnosed diseases from a predefined list of 15 candidate chronic conditions, defined according to standard clinical criteria. Linear mixed models were used to test cross-sectional and longitudinal associations between candidate biomarkers and multimorbidity.
  
  
  RESULTS
  At baseline, multimorbidity was significantly higher in older participants (p < .001) and higher IL-6, IL-1ra, TNF-α receptor II (TNFAR2), and lower dehydroepiandrosterone sulfate were associated with higher number of diseases, independent of age, sex, body mass index, and education. The rate of longitudinal increase in number of chronic diseases was significantly steeper in participants who were older at baseline (p < .001). In addition, higher baseline IL-6 and steeper increase of IL-6 levels were significantly and independently associated with a steeper increase in multimorbidity over time (p < .001 and p = .003, respectively). Sensitivity analyses, performed using 15 different models obtained by removing each of 15 conditions included in the original list of candidate diseases, confirmed that results were not driven by any specific condition.
  
  
  CONCLUSIONS
  Accumulation of chronic diseases accelerates at older ages and in persons with higher baseline levels and steeper increase over time of IL-6. High IL-6 and increase in IL-6 may serve as early warning sign to better target interventions aimed at reducing the burden of multimorbidity.
authors.affiliation: Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland. Department of Medical and Surgical Sciences, University of Bologna, Italy. elisa.fabbri@nih.gov.
authors.forename: Elisa
authors.initials: E
authors.lastname: Fabbri
authors.affiliation: Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
authors.forename: Yang
authors.initials: Y
authors.lastname: An
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Zoli
authors.affiliation: Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Simonsick
authors.affiliation: Department of Epidemiology and Public Health, Division of Gerontology, University of Maryland School of Medicine, Baltimore.
authors.forename: Jack M
authors.initials: JM
authors.lastname: Guralnik
authors.affiliation: Department of Geriatric Medicine, ASF - Firenze, Florence, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.affiliation: Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Boyd
authors.affiliation: Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D015897:Comorbidity; D003430:Cross-Sectional Studies; D005260:Female; D006728:Hormones / Q000097:blood*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D007558:Italy / Q000453:epidemiology; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D006728:Hormones; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6
keywords: Aging; Chronic diseases.; Inflammation; Interleukin-6; Multimorbidity
references.citation: J Gerontol A Biol Sci Med Sci. 2014 Jun;69 Suppl 1:S4-9
references.pmid: 24833586
references.citation: Lancet. 2012 Jul 7;380(9836):37-43
references.pmid: 22579043
references.citation: JAMA. 2012 Jun 20;307(23):2493-4
references.pmid: 22797447
references.citation: Blood. 2004 Oct 15;104(8):2263-8
references.pmid: 15238427
references.citation: Ann Clin Biochem. 2005 Jan;42(Pt 1):11-8
references.pmid: 15802027
references.citation: Am J Respir Crit Care Med. 2013 Apr 1;187(7):728-35
references.pmid: 23392440
references.citation: Chronic Illn. 2007 Sep;3(3):202-18
references.pmid: 18083677
references.citation: Acta Biomed. 2010;81 Suppl 1:19-29
references.pmid: 20518188
references.citation: J Clin Epidemiol. 1993 May;46(5):469-73
references.pmid: 8501473
references.citation: Aging (Albany NY). 2013 Jan;5(1):84-93
references.pmid: 23474627
references.citation: Prev Chronic Dis. 2013 Apr 25;10:E59
references.pmid: 23618539
references.citation: Am J Public Health. 2008 Jul;98(7):1198-200
references.pmid: 18511722
references.citation: J Clin Endocrinol Metab. 2011 Apr;96(4):1053-9
references.pmid: 21239514
references.citation: Prev Med. 2012 May;54 Suppl:S29-37
references.pmid: 22178471
references.citation: Ageing Res Rev. 2009 Jan;8(1):18-30
references.pmid: 18692159
references.citation: Circulation. 2000 Mar 7;101(9):1007-12
references.pmid: 10704168
references.citation: Eur J Gen Pract. 2008;14 Suppl 1:28-32
references.pmid: 18949641
references.citation: J Clin Epidemiol. 2001 Jul;54(7):661-74
references.pmid: 11438406
references.citation: Curr Opin Hematol. 2005 Mar;12(2):123-8
references.pmid: 15725902
references.citation: World J Biol Psychiatry. 2012 Dec;13(8):588-98
references.pmid: 21929378
references.citation: BMC Public Health. 2012 Aug 30;12:715
references.pmid: 22935268
references.citation: J Clin Epidemiol. 1998 May;51(5):367-75
references.pmid: 9619963
references.citation: J Am Geriatr Soc. 2000 Dec;48(12):1618-25
references.pmid: 11129752
references.citation: J Am Geriatr Soc. 2012 Oct;60(10):E1-E25
references.pmid: 22994865
references.citation: Ann Fam Med. 2012 Mar-Apr;10(2):142-51
references.pmid: 22412006
references.citation: Age (Dordr). 2011 Jun;33(2):209-17
references.pmid: 20617391
references.citation: J Gerontol A Biol Sci Med Sci. 2009 Dec;64(12):1268-74
references.pmid: 19713299
references.citation: JAMA. 2007 Sep 12;298(10):1160-2
references.pmid: 17848649
references.citation: J Gerontol A Biol Sci Med Sci. 2014 Jun;69 Suppl 1:S1-3
references.pmid: 24833579
references.citation: Clin Exp Immunol. 2003 Apr;132(1):24-31
references.pmid: 12653832
references.citation: J Lab Clin Med. 1998 Apr;131(4):316-23
references.pmid: 9579384
references.citation: Arch Gerontol Geriatr. 2012 May-Jun;54(3):e387-91
references.pmid: 22305611
references.citation: Blood. 2005 Mar 15;105(6):2294-9
references.pmid: 15572589
references.citation: BMC Health Serv Res. 2012 Apr 03;12:89
references.pmid: 22471952
references.citation: Circulation. 2001 Feb 20;103(7):947-53
references.pmid: 11181468
references.citation: CMAJ. 2013 Nov 5;185(16):E763-70
references.pmid: 24043651
references.citation: Aging Clin Exp Res. 2004 Jun;16(3):240-3
references.pmid: 15462468
references.citation: JAMA. 2010 Apr 7;303(13):1303-4
references.pmid: 20371790
references.citation: J Gerontol A Biol Sci Med Sci. 2014 Feb;69(2):165-73
references.pmid: 23689826
references.citation: Arch Intern Med. 2007 Nov 12;167(20):2249-54
references.pmid: 17998499
references.citation: J Gerontol A Biol Sci Med Sci. 2009 Feb;64(2):243-8
references.pmid: 19182229