Download PDF
Thromb Haemost 2001; 86(03): 791-799
DOI: 10.1055/s-0037-1616133
Review Articles
Schattauer GmbH

Increased Level of von Willebrand Factor Is Significantly and Independently Associated with Diabetes in Postinfarction Patients

Wojciech Zareba
1   Cardiology Unit, Department of Medicine
,
George Pancio
1   Cardiology Unit, Department of Medicine
,
Arthur J. Moss
1   Cardiology Unit, Department of Medicine
,
Vijay G. Kalaria
1   Cardiology Unit, Department of Medicine
,
Victor J. Marder
2   Vascular Medicine Center, Orthopedic Hospital, UCLA School of Medicine, Los Angeles, CA
,
Harvey J. Weiss
3   Division of Hematology and Oncology, St. Luke’s-Roosevelt Hospital Center, Columbia, University College of Physicians and Surgeons, New York City, NY, USA
,
Luc F. Miller Watelet
4   Department of Biostatistics of University of Rochester Medical Center, Rochester, NY
,
Charles E. Sparks
5   Department of Pathology
,
for THROMBO Investigators › Author AffiliationsThis study was supported by NIH grant 5R01HL-48259.
Further Information

Publication History

Received 05 June 2000

Accepted after resubmission 23 April 2001

Publication Date:
14 December 2017 (online)

    Permissions and Reprints

Summary

Diabetes is an established risk factor for reinfarction and cardiac death in postinfarction patients. Since the underlying mechanism of diabetes-related risk is not fully understood we aimed to evaluate the association between lipids, thrombogenic factors and diabetes in postinfarction patients. The study population consisted of 1,045 post-infarction patients (846 non-diabetic, 125 non-insulin- and 74 insulin-requiring diabetics) with the following blood tests performed 2 months after an index myocardial infarction: lipoprotein (a), apolipoprotein-B, apolipoprotein-A, cholesterol, HDL cholesterol, triglycerides, insulin, von Willebrand factor (vWF), fibrinogen, factor VII, D-dimer, and plasminogen activator inhibitor (PAI-1). After adjustment for relevant clinical covariates, non-insulin-requiring diabetes was significantly (p <0.05) associated with elevated levels of (odd ratios per 1 log unit increase in parenthesis) vWF (1.74) and PAI-1 (1.42) whereas insulin requiring diabetes was associated with even more elevated levels of vWF (4.68), but not with increased levels of PAI-1. No significant differences in lipid levels were observed among three groups. In conclusion, increased level of von Willebrand factor is significantly and independently associated with diabetes in postinfarction patients, suggesting that endothelial damage is the primary mechanisms contributing to an increased occurrence of vascular and cardiac events in diabetic postinfarction patients.

Keywords

Diabetes - Myocardial Infarction - vWF - PAI-1

* THROMBO Investigators are listed in the Appendix, p. 797.


 

  • References

  • 1 Jacoby R, Nesto R. Acute myocardial infarction in the diabetic patient: Pathophysiology, clinical course and prognosis. J Am Coll Cardiol 1992; 20: 736-44.
    CrossrefPubMedGoogle Scholar
  • 2 Behar S, Boyko V, Reicher-Reiss H, Goldbourt U. Ten-year survival after acute myocardial infarction: Comparison of patients with and without diabetes. Am Heart J 1997; 133: 290-5.
    CrossrefPubMedGoogle Scholar
  • 3 Aronson D, Rayfield E, Chesebro J. Mechanisms determining course and outcome of diabetic patients who have had acute myocardial infarction. Ann Intern Med. 1997; 126: 296-306.
    CrossrefPubMedGoogle Scholar
  • 4 Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors and 2-year cardiovascular mortality for men screened in the MRFIT trial. Diabetes Care 1993; 16: 434.
    CrossrefPubMedGoogle Scholar
  • 5 Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995; 92: 657-71.
    CrossrefPubMedGoogle Scholar
  • 6 DeWood MA, Spore J, Notske R, Mouser LT, Burroughs R, Golden MS, Lang HT. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Eng J Med 1980; 303: 897-900.
    CrossrefPubMedGoogle Scholar
  • 7 Vane JR, Anggard EE, Botting RM. Mechanisms of disease: regulatory functions of the vascular endothelium. N Engl J Med 1990; 322: 27-36.
    PubMedGoogle Scholar
  • 8 Meade TW, Mellos S, Brozovnic M, Miller GJ, Chakrabarti RR, North WR, Haines AP, Stirling Y, Imeson JD, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart study. Lancet 1986; 2: 533-7.
    PubMedGoogle Scholar
  • 9 Meade TW, North WRS. Population-based distributions of haemostatic variables. Br Med Bull 1977; 33: 283-8.
    CrossrefPubMedGoogle Scholar
  • 10 Jannson JH, Nilsson TK, Johnson O. von Willebrand factor in plasma: a novel risk factor for recurrent myocardial infarction and death. Br Heart J 1991; 66: 351-5.
    CrossrefPubMedGoogle Scholar
  • 11 Blann AD, McCollum CN. Von Willebrand factor, endothelial cell damage and ahterosclerosis. European Journal of Vascular Surgery. 1994; 8: 1045.
    PubMedGoogle Scholar
  • 12 Jansson JH, Olofsson BO, Nilsson TK. Predictive values of tissue plasminogen activator mass concentration on long-term mortality in patients with coronary artery disease: a 7-year follow-up. Circulation 1993; 88: 2030-34.
    CrossrefPubMedGoogle Scholar
  • 13 Hamsten A, DeFaire U, Walldius G, Dahlen G, Szamosi A, Landou C, Blomback M, Wiman B. Plasminogen activator inhibitor in plasma: Risk for recurrent myocardial infarction. Lancet 1987; 2: 3-9.
    PubMedGoogle Scholar
  • 14 Kannel WB, Wofl PA, Castelli WP, D’Agostino RB. Fibrinogen and risk of cardiovascular disease. The Framingham study. JAMA 1987; 258: 1183-86.
    CrossrefPubMedGoogle Scholar
  • 15 Dormandy J, Ernst E, Matrai A, Flute P. Hemorheological changes following acute myocardial infarction. Am Heart J 1982; 104: 1364-7.
    CrossrefPubMedGoogle Scholar
  • 16 Andreassen AK, Berg K, Torsvik H. Changes in Lp(a) lipoprotein and other plasma proteins during acute myocardial infarction. Clin Genet 1994; 46: 410-6.
    PubMedGoogle Scholar
  • 17 Niewiarowski S, Rao AK. Contribution of thrombogenic factors to the pathogenesis of atherosclerosis. Prog Cardiovasc Dis 1983; 26: 197-222.
    CrossrefPubMedGoogle Scholar
  • 18 Cortellaro M, Cofrancesco E, Boschetti C, Mussoni L, Donati MB, Cardillo M, Catalano M, Gabrielli L, Lombardi B, Specchia G. Increased fibrin turnover and high PAI-1 activity as predictors of ischemic events in athero-sclerotic patients: a case-controlled study. Atheroscler Thromb 1993; 13: 1412-7.
    CrossrefPubMedGoogle Scholar
  • 19 Bridges AB, McAlpine HM, Pringle TH, Mclaren M, Belch JF. Endothelial dysfunction in the acute myocardial infarction after reperfusion. Am Heart J 1993; 126: 451-52.
    CrossrefPubMedGoogle Scholar
  • 20 Abe S, Maruyama I, Arima S, Yamaguchi H, Okino H, Hamasaki S, Yamashita T, Nomoto K, Tahara M, Atsuchi Y. Increased heparin-releasable platelet factor 4 and D-dimer in patients one month after the onset of acute myocardial infarction: persistent activation of platelets and the coagulation/fibrinolytic system. Int J Cardiol 1994; 47 suppl S7-S12.
    CrossrefPubMedGoogle Scholar
  • 21 Francis CW, Connaghan DG, Scott WL, Marder VJ. Increased plasma concentration of crossed-linked fibrin polymers in acute myocardial infarction. Circulation 1987; 75: 1170-7.
    CrossrefPubMedGoogle Scholar
  • 22 Lee AJ, Lowe GD, Woodward M, Tunstall-Pedoe H. Fibrinogen in relation to personal history of prevalent hypertension, diabetes, stroke, intermittent claudication, coronary heart disease, and family history: the Scottish Heart Health Study. Br Heart J 1993; 69: 338-42.
    CrossrefPubMedGoogle Scholar
  • 23 Kannel WB, D’Agostino RB, Wilson WFP, Belanger AJ, Gagnon DR. Diabetes, fibrinogen and risk of cardiovascular disease: the Framingham experience. Am Heart J 1990; 120: 672-6.
    CrossrefPubMedGoogle Scholar
  • 24 Korsan-Bengtsen K, Wilhelmsen L, Elmfeldt D, Tibblin G. Blood coagulation and fibrinogen in men after a myocardial infarction compared with a representative population sample. Atherosclerosis 1972; 16: 83-8.
    CrossrefPubMedGoogle Scholar
  • 25 Ernst E, Resch KL. Fibrinogen as a cardiovascular risk factor: A meta-analysis and review of the literature. Ann Intern Med 1993; 118: 956-63.
    CrossrefPubMedGoogle Scholar
  • 26 The Caerphilly and Speedwell Collaborative Group.. Caerphilly collaborative heart disease studies. J Epidemiol Community Health 1984; 38: 259-62.
    CrossrefPubMedGoogle Scholar
  • 27 Carmassi F, Morale M, Puccetti R, De Negri F, Monzani F, Navalesi R, Mariani G. Coagulation and fibrinolytic system impairement insulin-dependent diabetes mellitus. Thrombosis Research 1992; 67: 643-54.
    CrossrefPubMedGoogle Scholar
  • 28 Mansfield MW, Strickland MH, Grant PJ. Plasminogen activator inhibitor (PAI-1) promoter polymorphism and coronary artery disease in NIDDM. Thromb Haemost 1995; 74: 1032-34.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Gough SCL, Grant PJ. The fibrinolytic system in diabetes mellitus. Diabetic Med 1991; 8: 898-905.
    CrossrefPubMedGoogle Scholar
  • 30 Stehouwer CDA, Nauta JJP, Zeldenrust GC, Hackeng WHL, Donker AJM, den Ottolander GJH. Albuminuria, cardiovascular disease, and endothelial dysfunction in non-insulin-dependent diabetes mellitus. Lancet 1992; 340: 319-323.
    CrossrefPubMedGoogle Scholar
  • 31 Juhan-Vague I, Alessi MC, Vague P. Increased plasminogen activator inhibitor 1 levels. A possible link between insulin resistance and atherothrombosis. Diabetologia 1991; 34: 457-62.
    CrossrefPubMedGoogle Scholar
  • 32 Juhan-Vague I, Vague P, Alessi MC, Badier C, Valadier J, Aillaud MF, Atlan C. Relationships between insulin, triglyceride, body mass index, plasminogen activator inhibitor-1. Diabetes Metab 1987; 13: 331-6.
    PubMedGoogle Scholar
  • 33 Bern MM, Cassani MP, Horton J, Rand L, Davis G. Changes of fibrinolysis and Factor VIII coagulant, antigen, and ristocetin cofactor in diabetes mellitus and atherosclerosis. Thromb Res 1980; 19: 831-9.
    CrossrefPubMedGoogle Scholar
  • 34 Sowers J, Epstein M. Diabetes Mellitus and hypertension: Emerging therapeutic perspectives. Cardiovasc Drug Rev 1995; 12: 149-210.
    PubMedGoogle Scholar
  • 35 Moss A, Goldstein R, Marder VJ, Sparks C, Oakes D, Greenberg H, Weiss HJ, Zareba W, Brown M, Liang C, Lichstein E, Little W, Gillespie J, Van Voorhees L, Krone R, Bodenheimer M, Hochman J, Dwyer E, Arora R, Marcus F, Miller-Watelet L. Case R: For THROMBO Research Group.. Thrombogenic factors and recurrent cardiac events. Circulation 1999; 99: 2517-22.
    CrossrefPubMedGoogle Scholar
  • 36 Clauss A. Gerinnungsphysiologische schnellmethode zur bestimmung des fibrinogens. Acta Haematol 1975; 17: 237-46.
    PubMedGoogle Scholar
  • 37 Weiss HJ, Pietu G, Meyer D, Rabinowitz R, Girma JP, Rogers J. Heterogenous abnormalities in multimeric structure, antigenic properties, and plasma/platelet content of FVII/vWF in classical (Type I) and three sub-types of variant (Type II) von Willebrands’s disease. J Lab Clin Med 1983; 101: 411-25.
    PubMedGoogle Scholar
  • 38 Marder VJ, Shulman NR. Clinical aspects of congenital factor VII deficiency. Am J Med 1964; 37: 182-94.
    CrossrefPubMedGoogle Scholar
  • 39 Morrissey JH, Macik BG, Neuenschwander PF, Comp PC. Quantitation of activated factor VII levels in plasma using a tissue factor mutant selectively deficient in promoting factor VII activation. Blood 1993; 81: 734-44.
    PubMedGoogle Scholar
  • 40 DeClerck PJ, Allessi MC, Verstreken M, Kruithof EKO, Juhan-Vague I, Collen D. Measurement of plasminogen activator inhibitor-1 in biological fluids with a murine monoclonal antibody-based enzyme-linked immunosorbent assay. Blood 1988; 71: 220-5.
    PubMedGoogle Scholar
  • 41 Elms MJ, Bunce IH, Bundesen PF, Gylatt DB, Webber AJ, Masci PP, Whitaker AN. Measurement of crosslinked fibrin degradation products: an immunoassay using monoclonal antibodies. Thromb Haemost 1983; 50: 591-4.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of preparation ultracentrifuge. Clin Chem 1972; 18: 499-502.
    PubMedGoogle Scholar
  • 43 Conlan MG, Folsom AR, Finch A, Davis CE, Sorlie P, Marcucci G, Wu KK. Associations of factor VIII and von Willebrand factor with age, race, sex, and risk factors for atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study. Thromb Haemost 1993; 70: 380-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 44 Collier A, Rumley A, Rumley AG, Paterson JR, Leach JP, Lowe GD. Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminuria. Diabetes 1992; 41: 909-13.
    CrossrefPubMedGoogle Scholar
  • 45 Potter van Loon BJ, Kluft K, Radder JK, Blankenstein MA, Meinders AE. The cardiovascular risk factor plasminogen activator inhibitor type-I is related to insulin resistance. Metabolism 1993; 42: 945-9.
    CrossrefPubMedGoogle Scholar
  • 46 Nagi DK, Krowler WC, Hanson RL, Mohamed Ali V, Yudkin JS. Plasminogen Activator Inhibitor (PAI-1) and Non-insulin-dependent Diabetes in PIMA Indians, South Asians, and Europeans. Thromb Haemost 1996; 76 (Suppl. 06) 921-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 47 Calles-Escandon J, Mirza SA, Sobel BE, Schneider DJ. Induction of hyperinsulinemia combined with hyperglycemia and hypertriglyceridemia inceases plasminogen activator inhibitor-1 in blood in normal human subjects. Diabetes 1998; 47: 290-3.
    CrossrefPubMedGoogle Scholar
  • 48 Ceriello A, Taboga C, Giacomello R, DeStasio G, Motz E. Fibrinogen plasma levels as a marker of thrombin activation in diabetes. Diabetes 1994; 43: 430-3.
    CrossrefPubMedGoogle Scholar
  • 49 Missov RM, Stolk RP, van der Bom JG, Hofman A, Bots ML, Pols HA. et al. Plasma fibrinogen in NIDDM: the Rotterdam Study. Diabetes Care 1996; 19 (Suppl. 02) 157-9.
    CrossrefPubMedGoogle Scholar
  • 50 Bruno G, Cavallo-Perin P, Bargero G, Borra M, D’Errico N, Panano G. Association of fibrinogen with glycemic control and albumin excretion rate in patients with non-insulin dependent diabetes mellitus. Ann Int Med 1996; 125 (Suppl. 08) 653-7.
    CrossrefPubMedGoogle Scholar
  • 51 Ginsberg NH. Lipoprotein physiology in nondiabetic and diabetic states: relationship to atherosclerosis. Diabetes Care 1991; 14: 839-55.
    CrossrefPubMedGoogle Scholar
  • 52 Howard BV. Lipoprotein metabolism in diabetes mellitus. J Lipid Res 1987; 28: 613-28.
    PubMedGoogle Scholar
  • 52 Taskinen MR. Quantitative and qualitative lipoprotein abnormalities in diabetes mellitus. Diabetes 1992; 41 (Suppl. 02) 12-7.
    PubMedGoogle Scholar