Abstract
Arterial thrombotic disease is the most frequent cause of morbidity and mortality in developed countries. There is good evidence that an imbalance in the hemostatic system can lead to arterial thrombosis. The arterial thrombotic diseases such as ischemic stroke or acute coronary syndrome arise from two processes, atherosclerosis and thrombosis. The identification of factors associated with the risk of developing arterial thrombosis will lead to a better understanding of the mechanism of thrombotic disease. Ultimately these data should be translated to the clinic for the prevention and treatment of arterial thromboembolic disease. Functional TAFI and the 46 C/T polymorphism in the gene F12 are two factors related to venous thomboembolic disease. Scarce information exists about their association with the risk of arterial thomboembolic disease such as ischemic stroke or acute coronary syndrome.We performed a case-control study with patients that were between 20 and 80 years old and each had at least one episode of ischemic stroke or acute coronary syndrome. The objectives were:
1- To determine the variations of Functional TAFI associated with age, sex, conventional cardiovascular risk factors and its correlation with other haemostatic risk factors.
2- To establish the association of Functional TAFI levels with the risk of ischemic stroke and acute coronary syndrome.
3- To establish the prevalence of the 46 C/T polymorphism in the F12gene in the Spanish population and the association of the different genotypes with Factor XIIc levels.
4- To investigate the association of the 46 C/T polymorphism in the F12 gene and Factor XII levels with the risk of ischemic stroke and acute coronary artery disease.
The results were:
1. Younger women showed lower levels of functional TAFI levels compared with older women. We did not find differences of functional TAFI levels among different age groups of men. No correlation of functional TAFI levels with conventional cardiovascular risk factors or other haemostatic factors were found. Only women with dyslipidemia showed higher levels of Functional TAFI.
2. Functional TAFI levels above 126% were associated with a 4-fold increased risk of acute coronary syndrome and Functional TAFI levels above 120% were associated with a 6-fold increased risk of ischemic stroke.
3. The prevalence of the genotype C/C of the 46 C/T polymorphism in the F12 gene in the Spanish population was 60% and this genotype was associated with Factor XIIc levels between 124% and 127%. The prevalence of the genotype C/T of the 46 C/T polymorphism in the F12 gene in the Spanish population was 38% and this genotype was associated with Factor XIIc levels between 95% and 98%. The prevalence of the genotype T/T of the 46 C/T polymorphism in the F12 gene in the Spanish population was 2%, and this genotype was associated with Factor XIIc levels between 58% and 52.5%.
4. Homozygosis of the T allele of 46 C/T polymorphism in the gene F12 was associated with a 4-fold increase risk of ischemic stroke and a 6-fold increase risk of acute coronary syndrome. Factor XII levels lower than 74% were associated with a 3-fold increase risk of ischemic stroke and Factor XII levels lower than 68% were associated with a 5-fold increase risk of acute coronary syndrome.
Therefore we may safely conclude that high Functional TAFI levels are associated with a high risk of arterial thromboembolic disease.Thus, it can be considered a new biomarker of thomboembolic risk. And the 46 C/T polymorphism in the F12 gene may be considered as a new genetic risk factor of arterial thromboembolic disease in the Spanish population and should be included in thrombophilic workups.
| Date of Award | 4 Jul 2005 |
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| Original language | Spanish |
| Supervisor | Miquel Lluis Rutllant Bañeres (Director) & Jorge Fontcuberta Boj (Director) |