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Inflammation, thrombosis and atherosclerosis: results of the Glostrup study
M P M de Maat1, E M Bladbjerg, T Drivsholm
1Department for Thrombosis Research, University of Southern Denmark and Department of Clinical Biochemistry, Ribe County Hospital, Esbjerg, Denmark. mpm.demaat@pg.tno.nl
Insights
Inflammation and thrombosis markers are linked to atherosclerosis severity. Higher C-reactive protein (CRP) correlated with increased intima-media thickness (IMT), while fibrinogen and d-dimer related to plaque occurrence.
Area of Science:
- Cardiovascular Disease Research
- Atherosclerosis Pathophysiology
- Hemostasis and Inflammation
Background:
- Inflammation and thrombosis are key in cardiovascular disease, linked to event risk.
- The association between inflammatory/hemostatic markers and atherosclerosis severity is understudied.
Purpose of the Study:
- To investigate the relationship between plasma inflammatory and hemostatic markers and atherosclerosis severity.
- To assess associations between genetic variations and atherosclerosis markers.
Main Methods:
- Evaluated 695 participants (325 men, 370 women) from the Danish Glostrup study.
- Assessed atherosclerosis via carotid intima-media thickness (IMT) and plaque occurrence.
- Measured plasma levels of CRP, fibrinogen, d-dimer, PAI-1, t-PA, FVII, and analyzed genetic variations (fibrinogen, PAI-1, t-PA, FVII, F XIII, MTHFR).
Main Results:
- Higher CRP levels were associated with increased IMT (P=0.04).
- Fibrinogen and d-dimer concentrations correlated with the number of plaques (P<0.01).
- Genetic variations in t-PA and MTHFR genes were linked to IMT.
Conclusions:
- Inflammation and thrombosis are associated with atherosclerosis severity in the Glostrup population.
- Findings suggest a role for these markers in atherosclerosis progression, indicated by IMT and plaque presence.
Abstract:
Inflammation and thrombosis are important mechanisms in cardiovascular disease, as illustrated by the consistent association between inflammatory and hemostatic variables and the risk of cardiovascular events in epidemiological studies. However, the relationship between plasma concentrations of inflammatory and hemostatic markers and the severity of atherosclerosis is not yet well studied. We have evaluated 325 men and 370 women of 60 years, participating in the Danish Glostrup study. We diagnosed atherosclerosis by ultrasonographic measurement of intima-media thickness (IMT) of the right carotid artery and the assessment of plaque occurrence. Plasma samples were analyzed for the concentration of C-reactive protein (CRP), fibrinogen, d-dimer, plasminogen activator inhibitor type-1 (PAI-1) antigen and activity, tissue-type plasminogen activator (t-PA) antigen and activity, factor VII (FVII) antigen, FVII coagulant activity (FVII:C) and activated FVII (FVIIa). DNA variations were determined for fibrinogen, PAI-1, t-PA, FVII, factor XIII and methylene tetrahydrofolate reductase (MTHFR). Subjects with high IMT (upper 10% of distribution, n = 63) had higher CRP levels [2.2 mg L-1 (SE 0.3)] than subjects with IMT in the lowest tertile (n = 217) [1.7 mg L-1 (SE 0.1), P = 0.04], whereas there was no association between the hemostatic variables and IMT. There was an association between fibrinogen and d-dimer concentrations and number of plaques (P < 0.01), whereas there were no associations between CRP and the other hemostatic variables and the number of plaques. Genetic variation in the t-PA and MTHFR gene was associated with IMT. In conclusion, in the Glostrup population study, thrombosis and inflammation are associated with the severity of atherosclerosis, as reflected by IMT and plaque occurrence.