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Thromb Haemost 2012; 107(05): 895-902
DOI: 10.1160/TH11-10-0703
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Variability of fibrinogen measurements in post-myocardial infarction patients

Results from the AIRGENE study center Augsburg
Jens Baumert
1   Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
,
Mahir Karakas
2   Department of Internal Medicine II -Cardiology, University of Ulm Medical Center, Ulm, Germany
,
Sonja Greven
3   Department of Statistics, Ludwig-Maximilians-Universität München, Munich, Germany
,
Regina Rückerl
1   Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
,
Annette Peters
1   Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
,
Wolfgang Koenig
2   Department of Internal Medicine II -Cardiology, University of Ulm Medical Center, Ulm, Germany
› Author Affiliations
Further Information

Publication History

Received: 13 October 2011

Accepted after major revision: 18 January 2012

Publication Date:
25 November 2017 (online)

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Summary

Elevated fibrinogen levels are strongly and consistently associated with incident coronary heart disease (CHD). A possible causal contribution of fibrinogen in the pathway leading to atherothrombotic cardiovascular disease complications has been suggested. However, for implementation in clinical practice, data on validity and reliability, which are still scarce, are needed that are still scarce, especially in subjects with a history of CHD. For the present study, levels of plasma fibrinogen were measured in 200 post-myocardial infarction (post-MI) patients aged 39–76 years, with approximately six blood samples collected at monthly intervals between May 2003 and March 2004, giving a total of 1,144 samples. Inter-individual variability (between-subject variance component, VCb and coefficient of variation, CVb), intra-individual and analytical variability (VCw+a and CVw+a), intraclass correlation coefficient (ICC) and the number of measurements required for an ICC of 0.75 were estimated to assess the reliability of serial fibrinogen measurements. Mean fibrinogen concentration of all subjects over all samples was 3.34 g/l (standard deviation 0.67). Between-subject variation for fibrinogen was VCb = 0.34 (CVb,=17.5%) whereas within-subject and analytical variation was estimated as VCw+a = 0.14 (CVw+a=11.0%). The variation was mainly explained by between-subject variability, shown by the proportion of total variance of 71.3%. Two different measurements were required to reach sufficient reliability, if subjects with extreme values were not excluded. The present study indicates a fairly good reproducibility of serial individual fibrinogen measurements in post-MI subjects.

Keywords

Myocardial infarction - fibrinogen - cardiovascular risk factors - biological variation - number of measurements
 

  • References

  • 1 Vasan RS. Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation 2006; 113: 2335-2362.
    CrossrefPubMedGoogle Scholar
  • 2 Kaptoge S, Di Angelantonio E, Lowe G. et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 2010; 375: 132-140.
    CrossrefPubMedGoogle Scholar
  • 3 Danesh J, Lewington S, Thompson SG. et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. J Am Med Assoc 2005; 294: 1799-809.
    PubMedGoogle Scholar
  • 4 Koenig W, Ernst E. The possible role of hemorheology in atherothrombogenesis. Atherosclerosis 1992; 94: 93-107.
    CrossrefPubMedGoogle Scholar
  • 5 Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999; 340: 115-126.
    CrossrefPubMedGoogle Scholar
  • 6 Tosetto A, Prati P, Baracchini C. et al. Association of plasma fibrinogen, C-reactive protein and G-455>A polymorphism with early atherosclerosis in the VITA Project cohort. Thromb Haemost 2011; 105: 329-335.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Koenig W. Fibrin(ogen) in cardiovascular disease: an update. Thromb Haemost 2003; 89: 601-609.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Folsom AR, Conlan MG, Davis CE. et al. Relations between hemostasis variables and cardiovascular risk factors in middle-aged adults. Atherosclerosis Risk in Communities (ARIC) Study Investigators. Ann Epidemiol 1992; 02: 481-494.
    CrossrefPubMedGoogle Scholar
  • 9 Uitte dW, de Visser MC, Houwing-Duistermaat JJ. et al. Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen gamma' levels. Blood 2005; 106: 4176-4183.
    CrossrefPubMedGoogle Scholar
  • 10 de Lange M, de Geus EJ, Kluft C. et al. Genetic influences on fibrinogen, tissue plasminogen activator-antigen and von Willebrand factor in males and females. Thromb Haemost 2006; 95: 414-419.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Thorand B, Baumert J, Doring A. et al. Sex differences in the relation of body composition to markers of inflammation. Atherosclerosis 2006; 184: 216-224.
    CrossrefPubMedGoogle Scholar
  • 12 Kolz M, Baumert J, Gohlke H. et al. Association study between variants in the fibrinogen gene cluster, fibrinogen levels and hypertension: results from the MON-ICA/KORA study. Thromb Haemost 2009; 101: 317-324.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Jacquemin B, Antoniades C, Nyberg F. et al. Common genetic polymorphisms and haplotypes of fibrinogen alpha, beta, and gamma chains affect fibrinogen levels and the response to proinflammatory stimulation in myocardial infarction survivors: the AIRGENE study. J Am Coll Cardiol 2008; 52: 941-952.
    CrossrefPubMedGoogle Scholar
  • 14 Dehghan A, Yang Q, Peters A. et al. Association of novel genetic Loci with circulating fibrinogen levels: a genome-wide association study in 6 population-based cohorts. Circ Cardiovasc Genet 2009; 02: 125-133.
    CrossrefPubMedGoogle Scholar
  • 15 Carty CL, Cushman M, Jones D. et al. Associations between common fibrinogen gene polymorphisms and cardiovascular disease in older adults. The Cardiovascular Health Study. Thromb Haemost 2008; 99: 388-395.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Stampfer MJ, Ridker PM, Dzau VJ. Risk factor criteria. Circulation 2004; 109: IV3-IV5.
    PubMedGoogle Scholar
  • 17 Thompson SG, Martin JC, Meade TW. Sources of variability in coagulation factor assays. Thromb Haemost 1987; 58: 1073-1077.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Blomback M, Eneroth P, Landgren BM. et al. On the intraindividual and gender variability of haemostatic components. Thromb Haemost 1992; 67: 70-75.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Chambless LE, McMahon R, Wu K. et al. Short-term intraindividual variability in hemostasis factors. The ARIC Study. Atherosclerosis Risk in Communities Intraindividual Variability Study. Ann Epidemiol 1992; 02: 723-733.
    CrossrefPubMedGoogle Scholar
  • 20 Marckmann P, Sandstrom B, Jespersen J. The variability of and associations between measures of blood coagulation, fibrinolysis and blood lipids. Atherosclerosis 1992; 96: 235-244.
    CrossrefPubMedGoogle Scholar
  • 21 Rosenson RS, Tangney CC, Hafner JM. Intraindividual variability of fibrinogen levels and cardiovascular risk profile. Arterioscler Thromb 1994; 14: 1928-1932.
    CrossrefPubMedGoogle Scholar
  • 22 Nguyen ND, Ghaddar H, Stinson V. et al. ARIC hemostasis study--IV. Intraindividual variability and reliability of hemostatic factors. The Atherosclerosis Risk in Communities (ARIC). Thromb Haemost 1995; 73: 256-260.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 de Maat M P, de Bart AC, Hennis BC. et al. Interindividual and intraindividual variability in plasma fibrinogen, TPA antigen, PAI activity, and CRP in healthy, young volunteers and patients with angina pectoris. Arterioscler Thromb Vasc Biol 1996; 16: 1156-1162.
    CrossrefPubMedGoogle Scholar
  • 24 De Bacquer D, De Backer G, Braeckman L. et al. Intra-individual variability of fibrinogen levels. J Clin Epidemiol 1997; 50: 393-399.
    CrossrefPubMedGoogle Scholar
  • 25 Salomaa V, Rasi V, Stengard J. et al. Intra- and interindividual variability of he-mostatic factors and traditional cardiovascular risk factors in a three-year follow-up. Thromb Haemost 1998; 79: 969-974.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Sakkinen PA, Macy EM, Callas PW. et al. Analytical and biologic variability in measures of hemostasis, fibrinolysis, and inflammation: assessment and implications for epidemiology. Am J Epidemiol 1999; 149: 261-267.
    CrossrefPubMedGoogle Scholar
  • 27 Rosenson RS, Mosca L, Staffileno BA. et al. Variability in fibrinogen measurements: an obstacle to cardiovascular risk stratification. Atherosclerosis 2001; 159: 225-230.
    CrossrefPubMedGoogle Scholar
  • 28 Rudez G, Meijer P, Spronk HM. et al. Biological variation in inflammatory and he-mostatic markers. J Thromb Haemost 2009; 07: 1247-1255.
    CrossrefPubMedGoogle Scholar
  • 29 Peters A, Schneider A, Greven S. et al. Air pollution and inflammatory response in myocardial infarction survivors: gene-environment interactions in a high-risk group. Inhal Toxicol 2007; 19 (Suppl. 01) 161-175.
    PubMedGoogle Scholar
  • 30 Löwel H, Meisinger C, Heier M. et al. The population-based acute myocardial infarction (AMI) registry of the MONICA/KORA study region of Augsburg. Gesundheitswesen 2005; 67 (Suppl. 01) S31-S37.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Alpert JS, Thygesen K, Antman E. et al. Myocardial infarction redefined--a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000; 36: 959-969.
    CrossrefPubMedGoogle Scholar
  • 32 Luepker RV, Apple FS, Christenson RH. et al. Case definitions for acute coronary heart disease in epidemiology and clinical research studies: a statement from the AHA Council on Epidemiology and Prevention; AHA Statistics Committee; World Heart Federation Council on Epidemiology and Prevention; the European Society of Cardiology Working Group on Epidemiology and Prevention; Centers for Disease Control and Prevention; and the National Heart, Lung, and Blood Institute. Circulation 2003; 108: 2543-2549.
    CrossrefPubMedGoogle Scholar
  • 33 Fleiss J. The Design and Analysis of Clinical Experiments. New York: NY; 1986
    Google Scholar
  • 34 Bland JM, Altman DG. Measuring agreement in method comparison studies. Stat Methods Med Res 1999; 08: 135-160.
    CrossrefPubMedGoogle Scholar
  • 35 Fraser CG, Harris EK. Generation and application of data on biological variation in clinical chemistry. Crit Rev Clin Lab Sci 1989; 27: 409-437.
    CrossrefPubMedGoogle Scholar
  • 36 Karakas M, Baumert J, Greven S. et al. Reproducibility in Serial C-Reactive Protein and Interleukin-6 Measurements in Post-Myocardial Infarction Patients: Results from the AIRGENE Study. Clin Chem 2010; 56: 861-864.
    CrossrefPubMedGoogle Scholar
  • 37 Khuseyinova N, Greven S, Rückerl R. et al. Variability of serial lipoprotein-associated phospholipase A2 measurements in post myocardial infarction patients: results from the AIRGENE Study Center Augsburg. Clin Chem 2008; 54: 124-130.
    PubMedGoogle Scholar
  • 38 Ricos C, Alvarez V, Cava F. et al. Current databases on biological variation: pros, cons and progress. Scand J Clin Lab Invest 1999; 59: 491-500.
    CrossrefPubMedGoogle Scholar
  • 39 Rückerl R, Peters A, Khuseyinova N. et al. Determinants of the acute-phase protein C-reactive protein in myocardial infarction survivors: the role of comorbidities and environmental factors. Clin Chem 2009; 55: 322-335.
    PubMedGoogle Scholar
  • 40 Brook RD, Rajagopalan S, Pope CA III. et al. Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation 2010; 121: 2331-2378.
    CrossrefPubMedGoogle Scholar