title: Association of D-dimer levels with all-cause mortality in a healthy adult population: findings from the MOLI-SANI study.
abstract: Elevated D-dimer levels are reportedly associated with higher risk of total mortality in patients with different diseases. We investigated whether a similar association could be found in a large, apparently healthy population. A large sample of individuals (N=17,359, 47% men, age ≥ 35 years) free of clinically recognized cardiovascular and cancer disease, for whom baseline D-dimer level was available, were studied within the MOLI-SANI cohort, randomly recruited from the general adult population of Southern Italy. The cohort was followed for a median of 4.2 years (73,807 person-years). D-dimer was measured in fresh citrated plasma by an automated latex-enhanced immunoassay. Hazard ratios were calculated using three Cox-proportional hazard models. Two hundred and eighty deaths were recorded. When modeled as a continuous variable, D-dimer level at baseline showed a non-linear association with mortality, whose incidence increased only in the upper quartile of the distribution (D-dimer ≥ 221 ng/mL). Thus, the group of individuals with D-dimer <221 ng/mL (75% of the population) acted as the reference group, while the remaining individuals were subdivided in tertiles and compared with the former group. Multivariable hazard ratios for mortality were 1.06, 1.45 and 1.97, respectively (P for trend <0.0001) across the three categories of increasing D-dimer concentration. The association was slightly attenuated, but still highly significant (P for trend 0.0002), after further adjustment for white blood cell count and C-reactive protein. In conclusion, Elevated D-dimer levels were independently associated with increased risk of death from any cause in an apparently healthy adult population.
authors: Laboratorio di Epidemiologia Genetica ed Ambientale, Fondazione di Ricerca e Cura “Giovanni Paolo II”, UniversitàCattolica del Sacro Cuore, Campobasso, Italy. dicastel@ngi.it
authors: Augusto
authors: A
authors: Di Castelnuovo
authors: Amalia
authors: A
authors: de Curtis
authors: Simona
authors: S
authors: Costanzo
authors: Mariarosaria
authors: M
authors: Persichillo
authors: Marco
authors: M
authors: Olivieri
authors: Francesco
authors: F
authors: Zito
authors: Maria Benedetta
authors: MB
authors: Donati
authors: Giovanni
authors: G
authors: de Gaetano
authors: Licia
authors: L
authors: Iacoviello
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends*; D011159:Population Surveillance / Q000379:methods*
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D
references: Lancet. 2002 Feb 23;359(9307):667-71
references: 11879863
references: Am J Hematol. 2009 Jun;84(6):349-53
references: 19472201
references: Haematologica. 2012 Aug;97(8):1158-64
references: 22371182
references: Nutr Metab Cardiovasc Dis. 2009 Dec;19(10):697-706
references: 19303267
references: Thromb Haemost. 1999 Aug;82(2):667-72
references: 10605766
references: Nutr Metab Cardiovasc Dis. 2012 Apr;22(4):347-54
references: 21093229
references: Int J Public Health. 2012 Jun;57(3):589-97
references: 22187041
references: Thromb Res. 2010 Apr;125 Suppl 2:S92-5
references: 20434016
references: Thromb Res. 2001 Jun 15;102(6):V215-24
references: 11516455
references: Circulation. 1994 Nov;90(5):2236-40
references: 7955179
references: Eur J Prev Cardiol. 2013 Oct;20(5):862-71
references: 22609891
references: Thromb Haemost. 2002 Jun;87(6):928-9
references: 12083497
references: Circulation. 1996 Aug 1;94(3):425-31
references: 8759084
references: Circulation. 2001 May 15;103(19):2323-7
references: 11352877
references: Arterioscler Thromb Vasc Biol. 1999 Mar;19(3):493-8
references: 10073948
references: Tumori. 1997 Nov-Dec;83(6):948-52
references: 9526590
references: J Am Coll Cardiol. 2010 Jun 15;55(24):2701-9
references: 20538163
references: Best Pract Res Clin Haematol. 2009 Mar;22(1):49-60
references: 19285272
references: Haematologica. 2011 Aug;96(8):1180-8
references: 21546503
references: Circulation. 1999 May 18;99(19):2517-22
references: 10330382
references: Thromb Haemost. 1998 Jan;79(1):129-33
references: 9459337
references: Lancet. 1986 Sep 6;2(8506):533-7
references: 2875280
references: J Thromb Haemost. 2006 May;4(5):1017-22
references: 16689753
references: Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):3321-5
references: 9409328
references: Int J Cardiol. 1995 Oct;51(3):245-51
references: 8586473
references: Circulation. 1997 Aug 19;96(4):1102-8
references: 9286936
references: Blood. 2003 Feb 15;101(4):1243-8
references: 12393393
references: Eur J Prev Cardiol. 2012 Aug;19(4):723-30
references: 21571772
references: Br J Haematol. 1998 Mar;100(4):758-63
references: 9531345
references: Thromb Haemost. 2007 Jul;98(1):126-8
references: 17598003
references: Arterioscler Thromb. 1993 Oct;13(10):1412-7
references: 8399077
references: Lancet. 1993 Jul 10;342(8863):84-6
references: 8100915
references: Arterioscler Thromb Vasc Biol. 2001 Apr;21(4):603-10
references: 11304479
references: Thromb Diath Haemorrh. 1975 Dec 15;34(3):652-60
references: 1108282
references: Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2793-9
references: 17023678