Rinske Loeffen1, Kristien Winckers2, Ian Ford3, J Wouter Jukema4, Michele Robertson3, David J Stott5, Henri M Spronk2, Hugo ten Cate2, Gordon D Lowe5. 1. Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands. rinske.loeffen@maastrichtuniversity.nl. 2. Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands. 3. The Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK. 4. Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. 5. Faculty of Medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK.
Abstract
BACKGROUND: Hypercoagulability may be an important contributor to the pathophysiology of atherosclerosis and atherothrombosis. As thrombin fulfills a central role in coagulation and links to several cellular mechanisms involved in arterial disease, we hypothesized that thrombin generation is associated with cardiovascular events in elderly patients. METHODS: We studied the relationship between plasma thrombin generation and incident coronary heart disease (CHD) and stroke in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). From this multicenter prospective cohort, 4,932 samples of subjects (70-82 years) with pre-existing vascular disease or risk factors were available for thrombin generation measurements. RESULTS: Within the 3.2 years of follow-up incident stroke and CHD was observed in 227 and 545 subjects, respectively. Baseline thrombin generation was significantly decreased in subjects with incident stroke compared with subjects without: normalized peak height 71.1±40.8% versus 82.3±44.9%, p = .0002, and normalized endogenous thrombin potential 79.1±23.3% versus 87.0±24.8%, p < .0001 (mean and SDs). Thrombin generation was independently and inversely associated with stroke risk: hazard ratio 0.71 (95%CI: 0.60-0.85), 0.68 (95%CI: 0.58-0.79), for normalized peak height and normalized endogenous thrombin potential, respectively (all p < .001). In subjects with incident CHD, thrombin generation was comparable to subjects without a coronary event. Only an increased normalized peak height was significantly associated with incident CHD (hazard ratio 1.17 [95% CI: 1.06-1.28], p = .002). CONCLUSIONS: We demonstrate that a delayed and decreased thrombin generation is a strong and independent predictor for stroke in elderly people at increased risk of vascular disease. However, no convincing consistent association could be demonstrated between thrombin generation and incident CHD.
BACKGROUND: Hypercoagulability may be an important contributor to the pathophysiology of atherosclerosis and atherothrombosis. As thrombin fulfills a central role in coagulation and links to several cellular mechanisms involved in arterial disease, we hypothesized that thrombin generation is associated with cardiovascular events in elderly patients. METHODS: We studied the relationship between plasma thrombin generation and incident coronary heart disease (CHD) and stroke in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). From this multicenter prospective cohort, 4,932 samples of subjects (70-82 years) with pre-existing vascular disease or risk factors were available for thrombin generation measurements. RESULTS: Within the 3.2 years of follow-up incident stroke and CHD was observed in 227 and 545 subjects, respectively. Baseline thrombin generation was significantly decreased in subjects with incident stroke compared with subjects without: normalized peak height 71.1±40.8% versus 82.3±44.9%, p = .0002, and normalized endogenous thrombin potential 79.1±23.3% versus 87.0±24.8%, p < .0001 (mean and SDs). Thrombin generation was independently and inversely associated with stroke risk: hazard ratio 0.71 (95%CI: 0.60-0.85), 0.68 (95%CI: 0.58-0.79), for normalized peak height and normalized endogenous thrombin potential, respectively (all p < .001). In subjects with incident CHD, thrombin generation was comparable to subjects without a coronary event. Only an increased normalized peak height was significantly associated with incident CHD (hazard ratio 1.17 [95% CI: 1.06-1.28], p = .002). CONCLUSIONS: We demonstrate that a delayed and decreased thrombin generation is a strong and independent predictor for stroke in elderly people at increased risk of vascular disease. However, no convincing consistent association could be demonstrated between thrombin generation and incident CHD.
Authors: Alan A Cohen; Véronique Legault; Georg Fuellen; Tamàs Fülöp; Linda P Fried; Luigi Ferrucci Journal: Exp Gerontol Date: 2017-07-16 Impact factor: 4.032
Authors: Rinske Loeffen; René van Oerle; Mathie P G Leers; Johannes A Kragten; Harry Crijns; Henri M H Spronk; Hugo Ten Cate Journal: PLoS One Date: 2016-07-15 Impact factor: 3.240
Authors: Marie-Claire F Kleinegris; Joke Konings; Jan W Daemen; Yvonne Henskens; Bas de Laat; Henri M H Spronk; Arina J Ten Cate-Hoek; Hugo Ten Cate Journal: Front Cardiovasc Med Date: 2017-04-20
Authors: C P D M de Breet; S Zwaveling; M J A Vries; R G van Oerle; Y M C Henskens; A W J Van't Hof; P E J van der Meijden; L Veenstra; H Ten Cate; R H Olie Journal: Front Cardiovasc Med Date: 2021-06-10