Alterations in the Coagulation System of Active Smokers from the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study

  • G. Delgado
  • R. Siekmeier
  • T. B. Grammer
  • B. O. Boehm
  • W. März
  • M. E. KleberEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 832)


Smoking is an important and preventable risk factor of cardiovascular diseases with effects on blood coagulation. Our aim was to analyze the influence of smoking on coagulation parameters. Concentrations or activities of blood coagulation factors were compared in 777 active smokers and 1,178 lifetime non-smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. The association with mortality was examined using Cox regression. The findings show that AS had a tendency toward thrombosis. They displayed significantly higher values for fibrinogen, soluble fibrinogen, factor XIII, and tissue factor pathway inhibitor; whereas FVII, FVIII, FXII, von Willebrand factor (vWF), and thrombomodulin were decreased. The Cox regression analysis showed fibrinogen, FVIII, vWF, thrombomodulin, and tissue factor pathway inhibitor to be independent risk factors for mortality in active smokers with hazard ratios of 1.16 (95 % CI: 1.02–1.31), 1.40 (1.22–1.59), 1.37 (1.22–1.56), 1.19 (1.07–1.31), and 1.22 (1.06–1.40) per increase of one standard deviation. We conclude that active smokers have an increased thrombogenic potential associated with significant changes in the coagulation system. Individual parameters of the coagulation system are independent predictors of mortality. Therefore, parameters of the coagulation system, apart from other risk factors for cardiovascular disease (e.g., lipids or life-style) should be determined for risk prediction in active smokers.


Cardiovascular disease 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. LURIC has received funding from the 6th Framework Program (integrated project Bloodomics, grant LSHM-CT-2004-503485) and from the 7th Framework Program (Atheroremo, grant agreement number 201668 and RiskyCAD, grant agreement number 305739) of the European Union.

Conflicts of Interest

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


  1. Anastasiou G, Gialeraki A, Merkouri E, Politou M, Travlou A (2012) Thrombomodulin as a regulator of the anticoagulant pathway: implication in the development of thrombosis. Blood Coagul Fibrinolysis 23:1–10PubMedCrossRefGoogle Scholar
  2. Ariens RA, Kohle HP, Mansfield MW, Grant PJ (1999) Subunit antigen and activity levels of blood coagulation factor XIII in healthy individuals. Relation to sex, age, smoking, and hypertension. Arterioscler Thromb Vasc Biol 19:2012–2016PubMedCrossRefGoogle Scholar
  3. Barua RS, Ambrose JA (2013) Mechanisms of coronary thrombosis in cigarette smoke exposure. Arterioscler Thromb Vasc Biol 33:1460–1467PubMedCrossRefGoogle Scholar
  4. Barua RS, Ambrose JA, Eales-Reynolds LJ, DeVoe MC, Zervas JG, Saha DC (2001) Dysfunctional endothelial nitric oxide biosynthesis in healthy smokers with impaired endothelium-dependent vasodilatation. Circulation 104:1905–1910PubMedCrossRefGoogle Scholar
  5. Barua RS, Ambrose JA, Saha DC, Eales-Reynolds LJ (2002) Smoking is associated with altered endothelial-derived fibrinolytic and antithrombotic factors: an in vitro demonstration. Circulation 106:905–908PubMedCrossRefGoogle Scholar
  6. Danaei G, Ding EL, Mozaffarian D, Taylor B, Rehm J, Murray CJ, Ezzati M (2009) The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med 6(4):e1000058PubMedCentralPubMedCrossRefGoogle Scholar
  7. Dotevall A, Johansson S, Wilhelmsen L (1994) Association between fibrinogen and other risk factors for cardiovascular disease in men and women. Results from the Goteborg MONICA survey 1985. Ann Epidemiol 4:369–374PubMedCrossRefGoogle Scholar
  8. Li M, Yu D, Williams KJ, Liu ML (2010) Tobacco smoke induces the generation of procoagulant microvesicles from human monocytes/macrophages. Arterioscler Thromb Vasc Biol 30:1818–1824PubMedCentralPubMedCrossRefGoogle Scholar
  9. Pretorius E, Oberholzer HM, van der Spuy WJ, Meiring JH (2010) Smoking and coagulation: the sticky fibrin phenomenon. Ultrastruct Pathol 34:236–239PubMedCrossRefGoogle Scholar
  10. Price JF, Mowbray PI, Lee AJ, Rumley A, Lowe GD, Fowkes FG (1999) Relationship between smoking and cardiovascular risk factors in the development of peripheral arterial disease and coronary artery disease: Edinburgh Artery Study. Eur Heart J 20:344–353PubMedCrossRefGoogle Scholar
  11. Winckers K, ten Cate H, Hackeng TM (2013) The role of tissue factor pathway inhibitor in atherosclerosis and arterial thrombosis. Blood Rev 27:119–132PubMedCrossRefGoogle Scholar
  12. Winkelmann BR, Marz W, Boehm BO, Zotz R, Hager J, Hellstern P, Senges J, LURIC Study Group (LUdwigshafen RIsk and Cardiovascular Health) (2001) Rationale and design of the LURIC study – a resource for functional genomics, pharmacogenomics and long-term prognosis of cardiovascular disease. Pharmacogenomics 2:S1–S73PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • G. Delgado
    • 1
  • R. Siekmeier
    • 2
  • T. B. Grammer
    • 1
  • B. O. Boehm
    • 3
    • 4
  • W. März
    • 1
    • 5
    • 6
  • M. E. Kleber
    • 1
    Email author
  1. 1.Fifth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of MannheimHeidelberg UniversityMannheimGermany
  2. 2.Drug Regulatory AffairsUniversity of BonnBonnGermany
  3. 3.Division of Endocrinology, Department of MedicineUniversity HospitalUlmGermany
  4. 4.LKC School of MedicineImperial College London and Nanyang Technological UniversitySingaporeSingapore
  5. 5.Clinical Institute of Medical and Chemical Laboratory DiagnosticsMedical University GrazGrazAustria
  6. 6.Synlab Academy, Synlab Services GmbHMannheimGermany

Personalised recommendations