Inverse association of the endogenous thrombin potential (ETP) with cardiovascular death : the Ludwigshafen Risk and Cardiovascular Health (LURIC) study
Background Coagulation and prothrombotic potential have genuinely been associated with increased cardiovascular risk. However, not all studies in this regard are conclusive. Some clinical trials have shown an increased frequency of cardiovascular complications in patients receiving direct thrombi...
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sg-ntu-dr.10356-1037872020-11-01T05:25:12Z Inverse association of the endogenous thrombin potential (ETP) with cardiovascular death : the Ludwigshafen Risk and Cardiovascular Health (LURIC) study Schneider, Jochen G. Isermann, Berend Kleber, Marcus E. Wang, Hongjie Boehm, Bernhard O. Grammer, Tanja B. Prueller, Florian Nawroth, Peter P. Maerz, Winfried Lee Kong Chian School of Medicine (LKCMedicine) DRNTU::Science::Biological sciences::Human anatomy and physiology Background Coagulation and prothrombotic potential have genuinely been associated with increased cardiovascular risk. However, not all studies in this regard are conclusive. Some clinical trials have shown an increased frequency of cardiovascular complications in patients receiving direct thrombin inhibitors. Previous data from human subjects after acute cardiovascular events showed an inverse association between the thrombin generation marker F1+2 and cardiovascular endpoints indicating that not the lowest, but a slightly elevated propensity for thrombin generation is associated with a lower risk of cardiovascular events. This observation has been supported by findings in animal models of atherosclerosis. Hence, we evaluated the association between the endogenous thrombin potential (ETP) and cardiovascular death (CVD) and markers of vascular dysfunction in a large prospective study with long-term follow up. Method After excluding patients receiving anticoagulants we tested ETP in 2196 participants (median follow-up 10 years) for its ability to predict vascular death (CVD). In addition, the association between ETP and sVCAM-1, sICAM-1, LpPLA2, hsCRP and SAA was determined. Results We observed an inverse association between ETP and CVD with the lowest hazard ratio in the 4th ETP quartile. The nadirs of sICAM-1 or sVCAM-1 were observed in the 3rd, for LpPLA2 in the 4th ETP quartile. Conversely, hsCRP and SAA were highest in the 4th quartile. Conclusions These results demonstrate that not the lowest ETP possible, but slightly higher levels are associated with a reduced risk of CVD and lower markers of endothelial dysfunction, suggesting a more complex role of thrombin in cardiovascular disease. Accepted version 2015-01-12T02:41:25Z 2019-12-06T21:20:15Z 2015-01-12T02:41:25Z 2019-12-06T21:20:15Z 2014 2014 Journal Article Schneider, J. G., Isermann, B., Kleber, M. E., Wang, H., Boehm, B. O., Grammer, T. B., et al. (2014). Inverse association of the endogenous thrombin potential (ETP) with cardiovascular death : the Ludwigshafen risk and cardiovascular health (LURIC) study. International journal of cardiology, 176(1), 139-144. 0167-5273 https://hdl.handle.net/10356/103787 http://hdl.handle.net/10220/24574 10.1016/j.ijcard.2014.07.026 en International journal of cardiology © 2014 The Authors. This is the author created version of a work that has been peer reviewed and accepted for publication by International Journal of Cardiology, the Authors. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [DOI:http://dx.doi.org/10.1016/j.ijcard.2014.07.026]. 6 p. application/pdf |
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DRNTU::Science::Biological sciences::Human anatomy and physiology Schneider, Jochen G. Isermann, Berend Kleber, Marcus E. Wang, Hongjie Boehm, Bernhard O. Grammer, Tanja B. Prueller, Florian Nawroth, Peter P. Maerz, Winfried Inverse association of the endogenous thrombin potential (ETP) with cardiovascular death : the Ludwigshafen Risk and Cardiovascular Health (LURIC) study |
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Background
Coagulation and prothrombotic potential have genuinely been associated with increased cardiovascular risk. However, not all studies in this regard are conclusive. Some clinical trials have shown an increased frequency of cardiovascular complications in patients receiving direct thrombin inhibitors. Previous data from human subjects after acute cardiovascular events showed an inverse association between the thrombin generation marker F1+2 and cardiovascular endpoints indicating that not the lowest, but a slightly elevated propensity for thrombin generation is associated with a lower risk of cardiovascular events. This observation has been supported by findings in animal models of atherosclerosis. Hence, we evaluated the association between the endogenous thrombin potential (ETP) and cardiovascular death (CVD) and markers of vascular dysfunction in a large prospective study with long-term follow up.
Method
After excluding patients receiving anticoagulants we tested ETP in 2196 participants (median follow-up 10 years) for its ability to predict vascular death (CVD). In addition, the association between ETP and sVCAM-1, sICAM-1, LpPLA2, hsCRP and SAA was determined.
Results
We observed an inverse association between ETP and CVD with the lowest hazard ratio in the 4th ETP quartile. The nadirs of sICAM-1 or sVCAM-1 were observed in the 3rd, for LpPLA2 in the 4th ETP quartile. Conversely, hsCRP and SAA were highest in the 4th quartile.
Conclusions
These results demonstrate that not the lowest ETP possible, but slightly higher levels are associated with a reduced risk of CVD and lower markers of endothelial dysfunction, suggesting a more complex role of thrombin in cardiovascular disease. |
author2 |
Lee Kong Chian School of Medicine (LKCMedicine) |
author_facet |
Lee Kong Chian School of Medicine (LKCMedicine) Schneider, Jochen G. Isermann, Berend Kleber, Marcus E. Wang, Hongjie Boehm, Bernhard O. Grammer, Tanja B. Prueller, Florian Nawroth, Peter P. Maerz, Winfried |
format |
Article |
author |
Schneider, Jochen G. Isermann, Berend Kleber, Marcus E. Wang, Hongjie Boehm, Bernhard O. Grammer, Tanja B. Prueller, Florian Nawroth, Peter P. Maerz, Winfried |
author_sort |
Schneider, Jochen G. |
title |
Inverse association of the endogenous thrombin potential (ETP) with cardiovascular death : the Ludwigshafen Risk and Cardiovascular Health (LURIC) study |
title_short |
Inverse association of the endogenous thrombin potential (ETP) with cardiovascular death : the Ludwigshafen Risk and Cardiovascular Health (LURIC) study |
title_full |
Inverse association of the endogenous thrombin potential (ETP) with cardiovascular death : the Ludwigshafen Risk and Cardiovascular Health (LURIC) study |
title_fullStr |
Inverse association of the endogenous thrombin potential (ETP) with cardiovascular death : the Ludwigshafen Risk and Cardiovascular Health (LURIC) study |
title_full_unstemmed |
Inverse association of the endogenous thrombin potential (ETP) with cardiovascular death : the Ludwigshafen Risk and Cardiovascular Health (LURIC) study |
title_sort |
inverse association of the endogenous thrombin potential (etp) with cardiovascular death : the ludwigshafen risk and cardiovascular health (luric) study |
publishDate |
2015 |
url |
https://hdl.handle.net/10356/103787 http://hdl.handle.net/10220/24574 |
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1683494055392051200 |