Sex-specific multivariable linear regression analysis adjusted for age, cardiovascular risk factors, cardiovascular diseases and therapy, was used to assess clinical determinants of thrombin generation. Another potential contributor to the prolonged lag time could be altered TFPI levels between subjects. However, assessing the TFPI levels in the presented cohort is a part of another study and beyond the scope of the current study. Figure 1. Open in a separate window Survival over Deoxygalactonojirimycin HCl 10 years for markers of thrombin generation above and below reference limits. Kaplan-Meier survival curves of the overall study sample demonstrating the 10-12 months survival of individuals with the thrombin generation parameters lag time (left panels), endogenous thrombin potential (ETP) (middle panels), and peak height (right panels) within the range of the reference group (green line), individuals above the 90th percentile of the reference group (blue line), and individuals above the 97.5th percentile of the reference group (red line), at 1 (upper panels) and 5 pM (lower panels) tissue factor (TF). For the lag occasions at both 1 and 5 pM TF, for 10 minutes). A previous small-scale analysis by Loeffen and colleagues16 showed TMEM2 that in order to eliminate residual platelets and microparticles, which may contribute to variability in TG results, double-centrifuged samples are preferable. We cannot, therefore, exclude that residual platelets and microparticles contributed to the observed associations between CVRF and TG parameters. Next, Deoxygalactonojirimycin HCl we had only cumulative mortality data available, so conclusions could not be made regarding associations between TG variables and specific causes of mortality. However, the standardized clinical investigation of the cardiovascular profile, standardized laboratory measurements of the large Gutenberg Health Study sample and availability of prospective Deoxygalactonojirimycin HCl mortality data are essential strenghts of our study, which delivers important evidence around the TG assay as a potential tool for improving risk stratification for CVD. In conclusion, this is the first, large, population-based study demonstrating an important relation between TG parameters, such as the time to minimum thrombin formed or the amount of thrombin formed, and total mortality. Further research is Deoxygalactonojirimycin HCl required around the underlying mechanism as well as to explore the potential role of the parameters as impartial biomarkers for increased mortality risk. The observed association of TG and traditional CVRF, particularly obesity, is an important obtaining in light of the growing globesity issue worldwide.31 Acknowledgments We are indebted to all study participants and all co-workers of the Gutenberg Health Study, who were involved in the planning and conduct of this study. Funding Statement em Funding: The Gutenberg Health Study is usually funded through the government of Rhineland-Palatinate (Stiftung RheinlandPfalz fr Development, contract AZ 961C386261/733), the research programs Wissen schafft Zukunft and Center for Translational Vascular Biology (CTVB) of the Johannes Gutenberg- University of Mainz, and its contract with Boehringer Ingelheim and PHILIPS Medical Systems, including unrestricted grants for the Gutenberg Health Study. This work was supported by the German Federal Ministry of Education and Research (BMBF 01EO1003) and the Center for Translational Vascular Biology (CTVB) of the University Medical Center Mainz (to PSW). HtC is usually a Fellow of the Gutenberg Deoxygalactonojirimycin HCl Research Foundation. /em .