Plasma Fibrinolysis Parameters in Smokers and Non-smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study

  • Graciela E. Delgado
  • Rüdiger Siekmeier
  • Bernhard K. Krämer
  • Winfried März
  • Marcus E. KleberEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 858)


Cardiovascular diseases (CVD) are an important cause of morbidity and mortality worldwide. Parameters of coagulation and fibrinolysis are risk factors of CVD and might be affected by cigarette smoking. Aim of our study was to analyze the effect of cigarette smoking on parameters of fibrinolysis in active smokers (AS) and life-time non-smokers (NS) of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study as well as the use of these parameters for risk prediction. We determined plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen (t-PA), protein C activity, and D-dimers in 3,316 LURIC patients. Smoking status was assessed by a questionnaire and measurement of plasma cotinine concentration. Cox regression was used to assess the effect of parameters on mortality. We found that of the 3,316 LURIC patients 777 were AS and 1,178 NS. Within the observation period of 10 years (median) 221 AS and 302 NS died. In male AS vs. NS, PAI-1 (19.0 (10.0–35.0) vs. 15.0 (9.0–29.0) U/ml; p = 0.026) and t-PA antigen (12.7 (9.6–16.3) vs. 11.6 (8.9–14.6) μg/l; p = 0.020) were slightly increased, while t-PA activity was slightly decreased (0.63 (0.30–1.05) vs. 0.68 (0.42–1.10) U/l; p = 0.005). In female AS vs. NS, t-PA antigen (10.5 (8.3–13.9) vs. 11.5 (8.8–15.0) μg/l; p = 0.025) and protein C (108.0 ± 24.1 % vs. 118.0 ± 25.7 %; p = 0.004) were decreased. All parameters except for protein C were predictive for mortality in AS. Fully adjusted hazard ratios (95 % CI) were 1.14 (1.04–1.25), 1.19 (1.06–1.34), and 1.29 (1.11–1.49) per 1SD increase for D-dimer, t-PA, and PAI-1, respectively. Including fibrinolysis parameters in risk prediction models for mortality improved the area-under-the-curve (AUC) significantly compared with the conventional risk factors. In conclusion, we found alterations in the fibrinolytic system in smokers, which were more pronounced in male AS. PAI-1, t-PA and D-dimers were significant predictors of mortality in AS in LURIC and should be included into the assessment of cardiovascular risk particularly in patients at risk.


Fibrinolysis Hemostasis Mortality Smoking Thrombosis 



We extend our appreciation to the participants of the LURIC study; without their collaboration this article would not have been written. We thank the LURIC study team who were either temporarily or permanently involved in patient recruitment as well as sample and data handling, in addition to the laboratory staff at the Ludwigshafen General Hospital and the Universities of Freiburg and Ulm, Germany. This work was supported by the 7th Framework Program (grant agreement number 201668 and RiskyCAD, grant agreement number 305739) of the European Union and by the INTERREG IV Oberrhein Program (Project A28, Genetic mechanisms of cardiovascular diseases) with support from the European Regional Development Fund (ERDF) and the Wissenschaftsoffensive TMO.

Conflicts of Interest

The authors declare no conflicts of interest in relation to this article.


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Graciela E. Delgado
    • 1
  • Rüdiger Siekmeier
    • 2
  • Bernhard K. Krämer
    • 1
  • Winfried März
    • 1
    • 3
    • 4
  • Marcus E. Kleber
    • 1
    • 5
    Email author
  1. 1.Fifth Department of Medicine, Medical Faculty MannheimHeidelberg UniversityHeidelbergGermany
  2. 2.Drug Regulatory Affairs, Pharmaceutical InstituteUniversity BonnBonnGermany
  3. 3.Clinical Institute of Medical and Chemical Laboratory DiagnosticsMedical University GrazGrazAustria
  4. 4.Synlab Academy, Synlab Services LLCMannheimGermany
  5. 5.Mannheim Institute for Public Health, Social and Preventive MedicineMannheimGermany

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