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The vitamin K antagonists (VKA) are necessary drugs of prevention and treatment of thrombo-embolic disease. The AVKAL study assesses the impact of VKA treatment on the aortic calcifications development. This is a biomedical research without health product, transversal and monocentric study which compares the aortic calcifications levels of two populations : one treated by VKA and the other which has never been treated by VKA.
The vitamin K antagonists exercise their anticoagulant effect by preventing the vitamin K dependant gamma-carboxylation of coagulation II, VII, IX and X factors which forms the final step of their activation.
They inhibit the vitamin K epoxide reductase VKORC1 enzyme, which is responsible of the vitamin K epoxide recycling in vitamin K hydroquinone (its reduced form). The carboxylation also can be inhibited by the Matrix Gla protein (MGP), inhibitor factor of vascular calcifications.
Warfarin (the most used VKA at the word level) is employed on animal for produce vascular calcifications by inhibiting the MGP activation.
Epidemiologic data indicate that warfarin could increase the calcifications of cardiac valves and coronary arteries. However, these studies were not interested in abdominal aorta's calcifications which are considered like an important marker of cardiovascular risk and did not concern the fluindione which is the most used VKA in France. Even if a class effect seems logical, the investigators can't dismiss the local effects, different to warfarin. In these studies, the calcifications assessment were rarely quantitative and the MGP levels were not measured. The vascular calcifications constitute a potential adverse effect of VKA which could limit their benefit in certain populations.
In this work there is an assumption that the aortic calcifications levels are upper in patients receiving VKA than in patients who are not receiving VKA and the aortic calcifications increase is owed to the non-activation of MGP.
The main objective is to assess if the taking of VKA is associated with the aortic calcifications development in patients receiving VKA.
Investigators will compare 2 populations: one group treated by VKA treatment for at least 6 months and one focus group which have never been treated by VKA treatment.
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| Measure | Description | Time Frame |
|---|---|---|
| Calcifications scores | Agatston's method | at inclusion |
| Measure | Description | Time Frame |
|---|---|---|
| Plasmatic concentrations in dp-ucMGP | The first measure of MGP is actually a measure of the dephosphorylated MGP [ dpMGP ] performed by ELISA | 12 months |
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Inclusion Criteria:
Exclusion Criteria:
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One group treated by VKA treatment for at least 6 months and one focus droup which have never been treated by VKA treatment.
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| Name | Affiliation | Role |
|---|---|---|
| Cedric RENARD | CHU Amiens | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Amiens | Amiens | 80054 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 6607731 | Background | Price PA, Urist MR, Otawara Y. Matrix Gla protein, a new gamma-carboxyglutamic acid-containing protein which is associated with the organic matrix of bone. Biochem Biophys Res Commun. 1983 Dec 28;117(3):765-71. doi: 10.1016/0006-291x(83)91663-7. | |
| 15265793 | Background | Schurgers LJ, Aebert H, Vermeer C, Bultmann B, Janzen J. Oral anticoagulant treatment: friend or foe in cardiovascular disease? Blood. 2004 Nov 15;104(10):3231-2. doi: 10.1182/blood-2004-04-1277. Epub 2004 Jul 20. |
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| ID | Term |
|---|---|
| D061205 | Vascular Calcification |
| ID | Term |
|---|---|
| D002114 | Calcinosis |
| D002128 | Calcium Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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A tube of blood on EDTA tubes of 6 ml will be taken at the elbow to the Clinical Research Center and then frozen at -80 ° . At the end of the study the tubes of all patients will be routed to VetAgro Sup Lyon in dry ice.
DNA will be extracted from EDTA tubes . It will be stored frozen in the laboratory until analysis of polymorphisms of interest, by PCR technique .
The promoter and the coding sequence of VKORC1 will be amplified by PCR and sequenced to detect the possible presence of SNPs
| 9743228 | Background | Price PA, Faus SA, Williamson MK. Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Arterioscler Thromb Vasc Biol. 1998 Sep;18(9):1400-7. doi: 10.1161/01.atv.18.9.1400. |
| 18841280 | Background | Schurgers LJ, Cranenburg EC, Vermeer C. Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb Haemost. 2008 Oct;100(4):593-603. |