Plasma Fibrinolysis Parameters in Smokers and Non-smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study
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.
KeywordsFibrinolysis 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.
- Barua RS, Ambrose JA, Srivastava S, DeVoe MC, Eales-Reynolds LJ (2003) Reactive oxygen species are involved in smoking-induced dysfunction of nitric oxide biosynthesis and upregulation of endothelial nitric oxide synthase: an in vitro demonstration in human coronary artery endothelial cells. Circulation 107:2342–2347PubMedCrossRefGoogle Scholar
- Kirtane AJ, Martinezclark P, Rahman AM, Ray KK, Karmpaliotis D, Murphy SA, Giugliano RP, Cannon CP, Antman EM, Roe MT, Harrington RA, Ohman EM, Braunwald E, Gibson CM (2005) Association of smoking with improved myocardial perfusion and the angiographic characterization of myocardial tissue perfusion after fibrinolytic therapy for ST-segment elevation myocardial infarction. J Am Coll Cardiol 45:321–323PubMedCrossRefGoogle Scholar
- Newby DE, McLeod AL, Uren NG, Flint L, Ludlam CA, Webb DJ, Fox KA, Boon NA (2001) Impaired coronary tissue plasminogen activator release is associated with coronary atherosclerosis and cigarette smoking: direct link between endothelial dysfunction and atherothrombosis. Circulation 103:1936–1941PubMedCrossRefGoogle Scholar