Thromb Haemost 1997; 77(04): 697-700
DOI: 10.1055/s-0038-1656036
Coagulation
Schattauer GmbH Stuttgart

Thrombin Generation Markers and Coronary Heart Disease Risk Factors in a Polish Population Sample

Jacek Musiał
The Department of Medicine and School of Public Health, Jagiellonian University School of Medicine, Krakow, Poland
,
Andrzej Pająk
The Department of Medicine and School of Public Health, Jagiellonian University School of Medicine, Krakow, Poland
,
Anetta undas
The Department of Medicine and School of Public Health, Jagiellonian University School of Medicine, Krakow, Poland
,
Ewa Kawalec
The Department of Medicine and School of Public Health, Jagiellonian University School of Medicine, Krakow, Poland
,
Roman Topór-Mądry
The Department of Medicine and School of Public Health, Jagiellonian University School of Medicine, Krakow, Poland
,
Tadeusz Pażucha
The Department of Medicine and School of Public Health, Jagiellonian University School of Medicine, Krakow, Poland
,
Marek Grzywacz
The Department of Medicine and School of Public Health, Jagiellonian University School of Medicine, Krakow, Poland
,
Andrzej Szczeklik
The Department of Medicine and School of Public Health, Jagiellonian University School of Medicine, Krakow, Poland
› Author Affiliations
Further Information

Publication History

Received 25 March 1996

Accepted after revision 12 December 1996

Publication Date:
11 July 2018 (online)

Summary

Thrombosis plays a major role in the development of atherosclerosis and its acute vascular complications. Epidemiological studies have shown that elevated levels of plasma fibrinogen are associated with an increased risk of coronary heart disease (CHD). It is not clear whether this association is linked to hemostatic functions of fibrinogen which serves as a substrate for thrombin. Generation of thrombin in vivo can be evaluated by measurement of its specific markers in plasma, i.e. thrombin-antithrombin III complex (TAT) and prothrombin fragment 1+2 (F1+2). We determined plasma levels of TAT and F1+2 in a population sample of southeastern Poland and evaluated relations of these markers with plasma fibrinogen, factor VII coagulant activity (FVIIc), and other known CHD risk factors. The population studied consisted of 215 men and 251 women, aged 43-75 years. Final analysis was performed on 195 men and 222 women.

The distribution of plasma TAT and F1+2 concentrations were highly skewed with the higher median values for women than for men. Log values of TAT correlated with log values of F1+2 in men (r = 0.27, p <0.01) and in women (r = 0.15, p <0.05). In the regression analysis both markers were positively related to age in women but not in men. After adjustment to age there was a positive relation between TAT and fibrinogen in both sexes. In women, but not in men, F1+2 showed a positive association with FVIIc. Total plasma cholesterol was negatively related to TAT in women only. There was no association between thrombin generation markers and plasma triglycerides, HDL-choles- terol, LDL-cholesterol, blood pressure, cigarette smoking and body mass index (BMI).

The association of plasma fibrinogen and FVIIc with thrombin generation markers points to an important role of the hemostatic system in the pathogenesis of atherosclerosis and coronary heart disease in humans.

 
  • References

  • 1 Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes: Part 1. N Engl J Med 1992; 326: 242-250
  • 2 Nachman RL. Thrombosis and atherogenesis: Molecular connections. Blood 1992; 79: 1897-1906
  • 3 Bauer K, Rosenberg RD. The pathophysiology of the prethrombotic state in humans: insights gained from studies using markers of hemostatic system activation. Blood 1987; 70: 343-349
  • 4 Prisco D. Markers of increased thrombin generation. Res Clin Lab 1990; 20: 217-225
  • 5 Ernst E, Resch KL. Fibrinogen as a cardiovascular risk factor: A meta analysis and review of a literature. Ann Intern Med 1993; 118: 956-963
  • 6 Eber B, Schumacher M. Fibrinogen: its role in the hemostatic regulation in atherosclerosis. Semin Thromb Hemost 1993; 19: 104-107
  • 7 Hamsten A. The hemostatic system and coronary heart disease. Thromb Res 1993; 70: 01-38
  • 8 Broadhurst P, Kelleher C, Hughes L, Imeson JD, Raftery EB. Fibrinogen, factor VII clotting activity and coronary artery disease severity. Atherosclerosis 1990; 85: 169-173
  • 9 Rywik S, Sznajd J, Przestalska H, Magdon M, Wagrowska H, Pajak A, Kulesza W, Celinski A, Kupsc W, Konarska R. Monitoring of cardiovascular incidence, fatality and mortality trends and their determinants – longitudinal study Pol-MONICA. Part I: Methodological principals of the study. PrzegLek 1985; 42: 250-255
  • 10 Rywik S, Pająk A, Kupsc W, Baczynska E, Sznajderman M, Celinski A, Kulesza W, Czemecka H, Przestalska H, Idzior B, Wagrowska H, Malczewska M, Mizera R. Monitoring of cardiovascular incidence, fatality and mortality trends and their determinants – longitudinal study PolMONICA. Part III: Principals of standardization and quality control. Przeg Lek 1985; 42: 280-286
  • 11 Warnick GR, Albers JJ. A comprehensive evaluation of the heparinmanganese precipitation procedure for estimating high density lipoprotein cholesterol. J Lipid Res 1987; 19: 65-70
  • 12 Friedewald WT, Levy RI, Friedrickson D. Estimation of the concentration of low-density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-504
  • 13 Kienast J, Thompson SG, Raskino C, Pelzer H, Fechtrup C, Ostermann H, van deLoo J. Prothrombin activation fragment 1+2 and thrombin antithrombin III complexes in patients with angina pectoris: relation to the presence and severity of coronary atherosclerosis. Thromb Haemost 1993; 70: 550-553
  • 14 Rugman FP, Jenkins JA, Duguid JK, Bolton MaggsP, Hay CRM. Prothrombin fragment F1+2: correlations with cardiovascular risk factors. Blood Coagulation and Fibrinolysis 1994; 5: 335-340
  • 15 Giansante C, Fiotti N, Cattin L, Da ColPG, Calabrese S. Fibrinogen, D-Dimer and thrombin-antithrombin complexes in a random population sample: Relationships with other cardiovascular risk factors. Thromb Haemost 1994; 71: 581-586
  • 16 Miller GJ, Bauer KA, Barzegar S, Foley AJ, Mitchell JP, Cooper JA, Rosenberg RD. The effects of quality and timing of venipuncture on markers of blood coagulation in healthy middle-aged men. Thromb Haemost 1995; 73: 82-86
  • 17 Hafner G, Schinzel H, Ehrental W, Wagner C, Konheiser U, Zotz R, Lotz J, Blank R, Weilemann LS, Prellwitz W. Influence of blood sampling from venipunctures and catheter systems on serial determinations of prothrombin activation fragment 1+2 and thrombin-antithrombin III complex. Ann Hematol 1993; 67: 121-125
  • 18 Cadroy Y, Pierrejean D, Fontan B, Sié P, Boneu B. Influence of aging on the activity of the hemostatic system: prothrombin fragment 1+2, thrombinantithrombin III complexes and D-dimers in 80 healthy subjects with age ranging from 20 to 94 years. Nouv Rev Fr Hematol 1992; 34: 43-46
  • 19 Estivals M, Pelzer H, Sié P, Pichon J, Boccalon H, Boneu B. Prothrombin fragment 1+2, thrombin-antithrombin III complex and D-dimers in acute deep vein thrombosis: effects of heparin treatment. Br J Haematol 1991; 78: 421-424
  • 20 Boisclair MD, Lane DA, Philippou H, Sheikh S, Hunt B. Thrombin production, inactivation and expression during open heart surgery measured by assays for activation fragments including a new ELISA for prothrombin fragment F1+2 . Thromb Haemost 1993; 70: 253-258
  • 21 Miller GJ, Wilkes HC, Meade TW, Bauer KA, Barzegar S, Rosenberg RD. Haemostatic changes that constitute the hypercoagulable state. Lancet 1991; 02: 1079
  • 22 Folsom AR. Epidemiology of fibrinogen. Eur Heart J 1995; 16 supplement A 21-23
  • 23 Lacoste L, Lam JYT, Hung J, Letchacovski G, Solymoss CB, Waters D. Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction. Circulation 1995; 92: 3172-3177
  • 24 Davi G, Ganci A, Avema M, Giammarresi C, Brabagallo C, Catalano I, Cala A, Notarbartolo A. Thromboxane biosynthesis, neutrophil and coagulative activation in type Ha hypercholesterolemia. Thromb Haemost 1995; 74: 1015-1019
  • 25 Wada H, Mori Y, Kaneko T, Wakita Y, Nakase T, Minimikawa K, Ohiwa M, Tamaki S, Tanigawa M, Kageyama S. Elevated plasma levels of vascular endothelial cell markers in patients with hypercholesterolemia. Am J Hematol 1993; 44: 112-116
  • 26 Kario K, Matsuo T. Lipid-related hemostatic abnormalities in the elderly: imbalance between coagulation and fibrinolysis. Atherosclerosis 1993; 103: 131-136
  • 27 Szczeklik A. Thrombin generation in myocardial infarction and hypercholesterolemia: effects of aspirin. Thromb Haemost 1995; 74: 77-80
  • 28 Szczeklik A, Musial J, Undas A, Swadźba J, Góra PF, Piwowarska W, Duplaga M. Inhibition of thrombin generation by aspirin is blunted in hypercholesterolemia. Arterioscler Thromb Vase Biol 1996; 16: 948-954
  • 29 Donders SH, Lustermans FA, van WerschJW. Prothrombin fragment 1.2 in both treated and untreated hypertensive patients. Neth J Med 1993; 43: 174-178