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A comparison of the associations between seven hemostatic or inflammatory variables and coronary heart disease
M Woodward1, A Rumley, P Welsh
1Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, UK.
Insights
Inflammatory markers like C-reactive protein (CRP) and interleukin-6 (IL-6) are linked to coronary heart disease (CHD) risk. D-dimer and IL-6 show potential for improving CHD risk prediction beyond traditional factors.
Area of Science:
- Cardiovascular Medicine
- Inflammation Biology
- Hemostasis Research
Background:
- Established links exist between hemostatic variables and coronary heart disease (CHD) risk.
- Some hemostatic variables may function as acute-phase reactants, influenced by inflammation.
Purpose of the Study:
- To investigate the association between hemostatic variables and inflammatory markers (CRP, IL-6).
- To assess the impact of adjusting for inflammatory markers and conventional risk factors on the association between hemostatic variables and CHD risk.
Main Methods:
- Nested case-control study within the Fletcher Challenge cohort (10,529 participants).
- 247 CHD cases and 473 controls matched for age and sex.
- Analysis of plasma levels of hemostatic variables, CRP, and IL-6, with multivariable adjustments.
Main Results:
- Most hemostatic variables correlated with CRP and IL-6, excluding VWF and Lp(a).
- Fibrinogen, VWF, t-PA, D-dimer, Lp(a), CRP, and IL-6 were associated with CHD risk.
- After adjusting for conventional risk factors, CRP, D-dimer, and IL-6 remained significant predictors of CHD risk.
Conclusions:
- Associations of fibrinogen, VWF, t-PA, and Lp(a) with CHD risk were attenuated by inflammatory markers and conventional risk factors.
- D-dimer and IL-6 showed sustained significant associations with CHD risk, even after multivariable adjustments.
- D-dimer and IL-6 may enhance the prediction of CHD risk independently of conventional 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.
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