Abstract 14102: Associations Between Thrombin Generation and the Risk of Cardiovascular and Cerebrovascular Events in the Elderly: Results From the PROSPER Study
Introduction: Studies suggest a contribution of hypercoagulability to the pathophysiology of atherosclerosis and -thrombosis. As thrombin fulfills a central role in coagulation and links to several mechanisms involved in arterial disease, we hypothesized that thrombin generation (TG) is associated with arterial events in the elderly.
Methods: We studied the relationship between plasma TG and cardio- and cerebrovascular events in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). From this multi-center prospective cohort, 4932 samples of subjects aged 70-82 with known cardiovascular risk factors or previous cardiovascular disease, were available for TG assessment (1 and 5 pM tissue factor trigger). The associations between TG and vascular endpoints were investigated using Cox proportional hazard models adjusted for country, treatment, age, sex, cardiovascular risk factors, IL-6, and CRP.
Results: Within the 3.2 years of follow-up 227 subjects had incident stroke (156 confirmed ischemic) and 545 subjects developed a coronary event. TG was decreased in subjects with a stroke during follow-up compared to subjects without; normalized peak height (nPeak) 71% vs. 82% and normalized endogenous thrombin potential (nETP) 79% vs. 87%. TG at 1 pM TF was independent and inversely associated with stroke risk with hazard ratios of 0.71 (95%CI: 0.60-0.85) and 0.68 (95%CI: 0.58-0.79), all P<0.001, for nPeak and nETP, respectively. The associations remained significant when triggering with 5 pM TF and did not change when analysis were restricted to ischemic strokes. In subjects with a coronary event during follow-up, TG was comparable with subjects without an event; nPeak 84% vs. 81%, and nETP 87% vs. 87%. Only an increased nPeak (1 pM TF) was significantly associated with cardiovascular risk (HR 1.17 [95% CI, 1.06-1.28], P=0.002).
Conclusions: In elderly people at increased risk of vascular disease, a delayed and decreased TG is a strong and independent risk factor for stroke. Only a limited association could be demonstrated between TG and coronary events. These results show there are vascular bed specific associations between TG and arterial events, suggesting different effects of TG in the etiologies for cardio- and cerebrovascular disease.
- © 2013 by American Heart Association, Inc.