BACKGROUND: While meta-analyses of prospective studies have established that plasma levels of several hemostatic variables are associated with the risk of coronary heart disease (CHD), these have been suggested to be acute-phase reactant proteins. This study examines their associations with inflammatory markers [C-reactive protein (CRP) and interleukin-6 (IL-6)] and the effect of adjustment on their associations with CHD risk. METHODS AND RESULTS: In a nested case-control study, 247 CHD cases and 473 controls were matched for age and sex from 10 529 men and women in the Fletcher Challenge cohort. Plasma levels of all hemostatic variables except von Willebrand factor (VWF) and lipoprotein (a) [Lp(a)] showed significant associations with CRP and IL-6. Fibrinogen, VWF, tissue plasminogen activator antigen (t-PA), D-dimer, Lp(a), CRP and IL-6 levels were significantly associated with risk of CHD. After adjustment for conventional risk factors, CRP, D-dimer and IL-6 levels were significantly associated with risk of CHD. On further adjustments for the other six hemostatic and inflammatory variables these associations were reduced, but remained significant for D-dimer and IL-6; odds ratios (95% CI), comparing the highest to lowest third, were 3.10 (1.25-7.67) and 2.79 (1.11-6.99), respectively. CONCLUSION: The associations of plasma levels of some hemostatic variables (fibrinogen, VWF, t-PA and Lp(a); but not fibrin D-dimer) with CHD risk are attenuated when inflammatory markers (CRP and IL-6) as well as conventional risk factors are included in multivariable analyses. D-dimer and IL-6 each have the potential to increase the prediction of CHD, in addition to conventional risk factors.
BACKGROUND: While meta-analyses of prospective studies have established that plasma levels of several hemostatic variables are associated with the risk of coronary heart disease (CHD), these have been suggested to be acute-phase reactant proteins. This study examines their associations with inflammatory markers [C-reactive protein (CRP) and interleukin-6 (IL-6)] and the effect of adjustment on their associations with CHD risk. METHODS AND RESULTS: In a nested case-control study, 247 CHD cases and 473 controls were matched for age and sex from 10 529 men and women in the Fletcher Challenge cohort. Plasma levels of all hemostatic variables except von Willebrand factor (VWF) and lipoprotein (a) [Lp(a)] showed significant associations with CRP and IL-6. Fibrinogen, VWF, tissue plasminogen activator antigen (t-PA), D-dimer, Lp(a), CRP and IL-6 levels were significantly associated with risk of CHD. After adjustment for conventional risk factors, CRP, D-dimer and IL-6 levels were significantly associated with risk of CHD. On further adjustments for the other six hemostatic and inflammatory variables these associations were reduced, but remained significant for D-dimer and IL-6; odds ratios (95% CI), comparing the highest to lowest third, were 3.10 (1.25-7.67) and 2.79 (1.11-6.99), respectively. CONCLUSION: The associations of plasma levels of some hemostatic variables (fibrinogen, VWF, t-PA and Lp(a); but not fibrin D-dimer) with CHD risk are attenuated when inflammatory markers (CRP and IL-6) as well as conventional risk factors are included in multivariable analyses. D-dimer and IL-6 each have the potential to increase the prediction of CHD, in addition to conventional risk factors.
Authors: Donna K Arnett; Robyn L McClelland; Alan Bank; David A Bluemke; Mary Cushman; Alexander J Szalai; Nishank Jain; Antoinette S Gomes; Susan R Heckbert; W Gregory Hundley; João A Lima Journal: Int J Mol Epidemiol Genet Date: 2011-11-28
Authors: G H Tofler; J Massaro; C J O'Donnell; P W F Wilson; R S Vasan; P A Sutherland; J B Meigs; D Levy; R B D'Agostino Journal: Thromb Res Date: 2016-02-03 Impact factor: 3.944
Authors: Sebhat Erqou; Stephen Kaptoge; Philip L Perry; Emanuele Di Angelantonio; Alexander Thompson; Ian R White; Santica M Marcovina; Rory Collins; Simon G Thompson; John Danesh Journal: JAMA Date: 2009-07-22 Impact factor: 56.272
Authors: Paul J Mills; Sonia Ancoli-Israel; Roland von Känel; Brent T Mausbach; Kirstin Aschbacher; Thomas L Patterson; Michael G Ziegler; Joel E Dimsdale; Igor Grant Journal: Brain Behav Immun Date: 2008-10-04 Impact factor: 7.217
Authors: Anna M Kucharska-Newton; David J Couper; James S Pankow; Ronald J Prineas; Thomas D Rea; Nona Sotoodehnia; Aravinda Chakravarti; Aaron R Folsom; David S Siscovick; Wayne D Rosamond Journal: Arterioscler Thromb Vasc Biol Date: 2009-10-01 Impact factor: 8.311