PDF herunterladen
Thromb Haemost 1993; 70(03): 380-385
DOI: 10.1055/s-0038-1649589
Original Article
Clinical Studies
Schattauer GmbH Stuttgart

Associations of Factor VIII and von Willebrand Factor with Age, Race, Sex, and Risk Factors for Atherosclerosis

The Atherosclerosis Risk in Communities (ARIC) Study
Maureen G Conlan
1   The University of Texas Medical School, Division of Hematology-Oncology, Houston, TX, USA
,
Aaron R Folsom
2   The Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, MN
,
Andrea Finch
1   The University of Texas Medical School, Division of Hematology-Oncology, Houston, TX, USA
,
C E Davis
3   The University of North Carolina, Collaborative Studies Coordinating Center, Chapel Hill
,
Paul Sorlie
4   The National Heart, Lung, and Blood Institute, Division of Epidemiology and Clinical Applications, Federal Building, Bethesda, USA
,
Gretchen Marcucci
3   The University of North Carolina, Collaborative Studies Coordinating Center, Chapel Hill
,
Kenneth K Wu
1   The University of Texas Medical School, Division of Hematology-Oncology, Houston, TX, USA
,
For the ARIC Study Investigators › Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 19. April 1991

Accepted after revision 05. April 1993

Publikationsdatum:
05. Juli 2018 (online)

Auch verfügbar auf
  als PDF herunterladen  Lizenzen und Reprints

Summary

Several coagulation proteins have been implicated as possible risk factors for the development of atherosclerotic diseases, among which are factor VIII and von Willebrand factor. As part of the Atherosclerosis Risk in Communities (ARIC) Study, a prospective study designed to assess risk factors for the development of atherosclerotic diseases, baseline measurements of factor VIII and von Willebrand factor (vWF) were performed to determine their relationship to the development of atherosclerosis. We herein report the associations of factor VIII and vWF with constitutional, lifestyle, and biochemical factors. Factor VIII and vWF were strongly correlated with each other (r = 0.73), and, therefore, had similar associations with risk factors. Mean levels of both factors were higher in women than in men, in blacks than in whites, and increased with age. In univariate analysis, both were positively associated with diabetes, body mass index, waist-to-hip ratio, serum insulin, and plasma triglycerides. Both were negatively associated with alcohol intake, educational level, physical activity (with some exceptions), and HDL-cholesterol. No correlations were observed between factor VIII or vWF and plasma LDL-cholesterol or lipoprotein(a). Although factor VIII was negatively associated with smoking in both sexes, vWF was not associated with smoking status. Most of these associations were confirmed in multivariate analysis. The strongest associations observed were of factor VIII and vWF with race and diabetes. In multivariate analysis, blacks had factor VIII and vWF levels 15 to 18 percentage points higher than whites, and diabetics had factor VIII and vWF levels 11 to 18 percentage points higher than non-diabetics. These associations must be taken into account when analyzing the possible role of factor VIII and vWF in the development of atherosclerotic diseases.

Support was provided by National Heart, Lung, and Blood Institute Contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022


 

  • References

  • 1 Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984; 311: 501-505
    CrossrefPubMedGoogle Scholar
  • 2 Meade TW, Mellows S, Brozovic M, Miller GJ, Chakrabarti RR, North WRS, 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: 533-537
    PubMedGoogle Scholar
  • 3 Kannel WB, Wolf PA, Castelli WP, D’Agostino RB. Fibrinogen and risk of cardiovascular disease. The Framingham Study. JAMA 1987; 258: 1183-1186
    CrossrefPubMedGoogle Scholar
  • 4 Egeberg O. Clotting factor levels in patients with coronary atherosclerosis. Scand J Clin Lab Invest 1962; 14: 253-258
    CrossrefPubMedGoogle Scholar
  • 5 Cooperberg AA, Teitelbaum JI. The concentration of antihemophilic globulin (AHG) in patients with coronary artery disease. Ann Int Med 1961; 54: 899-907
    CrossrefPubMedGoogle Scholar
  • 6 Bern MM, Cassani MP, Horton J, Rand L, Davis G. Changes of fibrinolysis and Factor VIII coagulant, antigen, and ristocetin co-factor in diabetes mellitus and atherosclerosis. Thromb Res 1980; 19: 831-839
    CrossrefPubMedGoogle Scholar
  • 7 Rak K, Beck P, Udvardy M, Pfliegler G, Misz M, Boda Z. Plasma levels of beta-thromboglobulin and Factor VIII-related antigen in diabetic children and adults. Thromb Res 1983; 29: 155-162
    CrossrefPubMedGoogle Scholar
  • 8 Sugrue DD, Trayner I, Thompson GR, Vere VJ, Imeson JD, Stirling Y, Meade TW. Coronary artery disease and haemostatic variables in heterozygous familial hypercholesterolemia. Br Heart J 1985; 53: 265-268
    CrossrefPubMedGoogle Scholar
  • 9 Myreng Y, Aursnes I, Hjermann I, Stormorken H, Sund T, Hellem A. Von Willebrand Factor and cardiovascular risk. Thromb Res 1986; 41: 867-871
    CrossrefPubMedGoogle Scholar
  • 10 Stormorken H, Erikssen J. Plasma antithrombin III and Factor VIII antigen in relation to angiographic findings, angina and blood groups in middle-aged men. Thromb Haemostas 1977; 38: 874-880
    PubMedGoogle Scholar
  • 11 Hamsten A, Blomb ck, Wiman B, Svensson J, Szamosi A, DeFaire U, Mettinger L. Haemostatic function in myocardial infarction. Br Heart J 1986; 55: 58-66
    CrossrefPubMedGoogle Scholar
  • 12 Schmitz-Huebner U, Thompson SG, Balleisen L, Fechtrup C, Grosse-Heitmeyer W, Kirchhof B, Most E, Müller U-S, Seiffert C, Seiffert D, van de LooJ. Lack of association between haemostatic variables and the presence or the extent of coronary atherosclerosis. Br Heart J 1988; 59: 287-291
    CrossrefPubMedGoogle Scholar
  • 13 Meade TW, Chakrabarti R, Haines AP, North WRS, Stirling Y, Thompson SG. Haemostatic function and cardiovascular death: Early results of a prospective study. Lancet 1980; 1: 1050-1054
    PubMedGoogle Scholar
  • 14 ARIC Investigators. The Atherosclerosis Risk in Communities (ARIC) Study: Design and objectives. Am J Epidemiol 1989; 129: 687-702
    CrossrefPubMedGoogle Scholar
  • 15 Papp AC, Hatzakis H, Bracey A, Wu KK. ARIC hemostasis study-I. Development of a blood collection and processing system suitable for multicenter hemostatic studies. Thromb Haemostas 1989; 66: 15-29
    PubMedGoogle Scholar
  • 16 National Heart, Lung, and Blood Institute. Atherosclerosis Risk in Communities (ARIC) Study Protocol, Manual 9: Hemostasis Determinations. ARIC Study Coordinating Center, School of Public Health, University of North Carolina, Suite 203, NCNB Plaza, 137 E. Franklin Street, Chapel Hill, North Carolina
    PubMedGoogle Scholar
  • 17 Nagele U, Hagele EO, Sauer G, Wiedemann E, Lehmann P, Wahlefeld AW, Gruber W. Reagent for the enzymatic determination of serum total triglycerides with improved lipolytic efficiency. J Clin Chem Biochem 1984; 22: 165-174
    PubMedGoogle Scholar
  • 18 Siedel J, Hegele EO, Ziegenhom J, Wahlefeld AW. Reagent for the enzymatic determination of total serum Cholesterol with improved lipolytic efficiency. Clin Chem 1983; 29: 1075-1080
    PubMedGoogle Scholar
  • 19 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein Cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502
    CrossrefPubMedGoogle Scholar
  • 20 Warnick GR, Benderson JM, Albers JJ. Quantitation of high-density-lipoprotein subclasses after Separation by dextran sulfate and Mg2+ precipitation (Abstract). Clin Chem 1982; 28: 1574
    PubMedGoogle Scholar
  • 21 Gaubitz JW, Cushing GL, Morrisett JD. Quantitation, isolation and characterization of human lipoprotein (a). Methods Enzymol 1986; 129: 167-186
    PubMedGoogle Scholar
  • 22 Baecke JAH, Burema J, Frijters JER. A short questionnaire for the measurement of habitual physical activity in epidemiologic studies. Am J Clin Nutr 1982; 36: 936-942
    CrossrefPubMedGoogle Scholar
  • 23 SAS User’ Guide. Statistics. Cary, NC: SAS Institute, Inc 1985
    PubMedGoogle Scholar
  • 24 Chakrabarti R, Brozovic M, North WRS, Stirling Y, Meade TW. Effects of age on fibrinolytic activity and factors V, VII and VIII. Proc R Soc Med 1975; 68: 267-268
    PubMedGoogle Scholar
  • 25 Jeremic M, Weisert O, Gedde-Dahl TW. Factor VIII (AHG) levels in 1016 regular blood donors. The effects of age, sex, and ABO blood groups. Scand J Clin Lab Invest 1976; 36: 461-466
    CrossrefPubMedGoogle Scholar
  • 26 Cooperberg AA, Teitelbaum J. The concentration of antihaemophilic globulin (AHG) related to age. Br J Haematol 1960; 6: 281-287
    CrossrefPubMedGoogle Scholar
  • 27 Pitney WR, Kirk RL, Arnold BJ, Stenhouse NS. Plasma antihaemophilic factor (factor VIII) concentrations in normal families. Br J Haematol 1962; 8: 421-428
    CrossrefPubMedGoogle Scholar
  • 28 Balleisen L, Bailey J, Epping P-H, Schulte H, van de LooJ. Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population: I. Baseline data on the relation to age, gender, body-weight, smoking, alcohol, pill-using, and menopause. Thromb Haemostas 1985; 54: 475-479
    PubMedGoogle Scholar
  • 29 Christe M, Fritschi J, Lämmle B, Tran TH, Marbet GA, Berger W, Duckert F. Fifteen coagulation and fibrinolysis parameters in diabetes mellitus and in patients with vasculopathy. Thromb Haemostas 1984; 52: 138-143
    PubMedGoogle Scholar
  • 30 Meade TW, Brozovic M, Chakrabarti R, Haines AP, North WRS, Stirling Y. Ethnie group comparisons of variables associated with ischaemic heart disease. Br Heart J 1978; 40: 789-795
    CrossrefPubMedGoogle Scholar
  • 31 Kerr CB, Preston AE, Barr A, Biggs R. Further studies on the inheritance of factor VIII. Br J Haematol 1966; 12: 212-233
    CrossrefPubMedGoogle Scholar
  • 32 Preston AE, Barr A. The plasma concentration of factor VIII in the normal population. II. The effects of age, sex and blood group. Br J Haematol 1964; 10: 238-245
    CrossrefPubMedGoogle Scholar
  • 33 Meade TW, North WRS, Chakrabarti R, Haines AP, Stirling Y. Population-based distributions of haemostatic variables. Br Med Bull 1977; 33: 283-288
    CrossrefPubMedGoogle Scholar
  • 34 Wahlberg TB, Blombäck M, Magnusson D. Influence of sex, blood group, secretor character, smoking habits, acetylsalicylic acid, oral contraceptives, fasting and general health state on blood coagulation variables in randomly selected young adults. Haemostasis 1984; 14: 312-319
    PubMedGoogle Scholar
  • 35 Chetty N, Reavis S, Solomons HD, Pienaar N, Baynes R, Meriwether D, Atkinson PM. Platelet aggregations, fatty acids, clotting factors and serum lipids in rural and urban blacks, and urban whites in South Africa. Artery 1988; 15: 234-243
    PubMedGoogle Scholar
  • 36 Walker RH. (ed) Technical Manual of the American Association of Blood Banks. l0.. Arlington, VA: American Association of Blood Banks; 1990. Chapter 10
    Google Scholar
  • 37 Lufkin EG, Fass DN, O’Fallon WM, Bowie EJW. Increased von Willebrand factor in diabetes mellitus. Metabolism 1979; 28: 63-66
    CrossrefPubMedGoogle Scholar
  • 38 Coller BS, Frank RN, Milton RC, Gralnick HR. Plasma cofactors of platelet function: Correlation with diabetic retinopathy and hemoglobins Ala-c. Studies in diabetic patients and normal persons. Ann Intern Med 1978; 88: 311-316
    CrossrefPubMedGoogle Scholar
  • 39 Mayne EE, Bridges JM, Weaver JA. Platelet adhesiveness, plasma fibrinogen and factor VIII levels in diabetes mellitus. Diabetologia 1970; 6: 436-440
    CrossrefPubMedGoogle Scholar
  • 40 Borkenstein MH, Muntean WE. Elevated factor VIII activity and factor VHI-related antigen in diabetic children without vascular disease. Diabetes 1982; 31: 1006-1009
    CrossrefPubMedGoogle Scholar
  • 41 Porta M, Townsend C, Clover GM, Nanson M, Alderson AR, McCraw A, Kohner EM. Evidence for functional endothelial cell damage in early diabetic retinopathy. Diabetologia 1981; 20: 597-601
    PubMedGoogle Scholar
  • 42 Gensini GF, Abbate R, Favilla S, Neri SerneriGG. Changes of platelet function and blood clotting in diabetes mellitus. Thromb Haemostas 1979; 42: 983-993
    PubMedGoogle Scholar
  • 43 Pandolfi M, Almér L-O, Holmberg L. Increased von Willebrand-antihaemophilic factor A in diabetic retionopathy. Acta Ophthal 1974; 52: 823-827
    PubMedGoogle Scholar
  • 44 Vukovich TC, Schernthaner G, Knöbl PN, Hay U. The effect of nearnormoglycemic control on plasma factor VHI/von Willebrand factor and fibrin degradation products in insulin-dependent diabetic patients. J Clin Endocrinol Metab 1989; 69: 84-89
    CrossrefPubMedGoogle Scholar
  • 45 Borsey DQ, Prowse CV, Gray RS, Dawes J, James K, Elton RA, Clarke BF. Platelet and coagulation factors in proliferative diabetic retinopathy. J Clin Pathol 1984; 37: 659-664
    CrossrefPubMedGoogle Scholar
  • 46 Hughes A, McVerry BA, Wilkinson L, Goldstone AH, Lewis D, Bloom A. Diabetes, a hypercoagulable Haemostatic variables in newly diagnosed type 2 diabetic patients. Acta Haematol 1983; 69: 254-259
    CrossrefPubMedGoogle Scholar
  • 47 Gamba G, Solerte SB, Grignani G, Pacchiarini L, Montani N, Ferrari E. Haemostatic variables, serum lipid abnormalities and vascular complications in diabetes mellitus: A 5-year follow-up study. Blut 1988; 56: 257-260
    CrossrefPubMedGoogle Scholar
  • 48 Iso H, Folsom AR, Wu KK, Finch A, Munger RG, Sato S, Shimamoto T, Terao A, Komachi Y. Hemostatic variables in Japanese and Caucasian men. Plasma fibrinogen, factor VIIc, factor VIII c, and von Willebrand factor and their relations to cardiovascular disease risk factors. Am J Epidemiol 1989; 130: 925-934
    CrossrefPubMedGoogle Scholar
  • 49 Balleisen L, Assmann G, Bailey J, Epping P-H, Schulte H, van de LooJ. Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population II. Baseline data on the relation to blood pressure, blood glucose, uric acid, and lipid fractions. Thromb Haemostas 1985; 54: 721-723
    PubMedGoogle Scholar
  • 50 Korsan-Bengtsen K, Bengtsson C, Tibblin E. Blood coagulation, fibrinolysis and platelet function in women aged 38, 46, 50, 54 and 60. The study of women in Gothenburg 1968-1969. Acta Med Scand 1973; 193: 543-546
    PubMedGoogle Scholar
  • 51 Meilahn E, Kuller LH, Kiss JE, Matthews KA, Lewis JH. Coagulation parameters among pre- and postmenopausal women (Abstract). Am J Epidemiol 1988; 128: 908
    PubMedGoogle Scholar
  • 52 Mink IB, Courey NG, Niswander KR, Moore RH, Lillie MA, Ambrus JL. Progestational agents and blood coagulation. V. Changes induced by sequential oral contraceptive therapy. Am J Obstet Gynecol 1974; 119: 401-405
    CrossrefPubMedGoogle Scholar
  • 53 Egeberg O, Owren PA. Oral contraception and blood coagulability. Br Med J 1963; 1: 220-221
    CrossrefPubMedGoogle Scholar
  • 54 Jansson J-H, Nilsson TK, Johnson O. Von Willebrand factor in plasma: a novel risk factor for recurrent myocardial infarction and death. Br Heart J 1991; 66: 351-355
    CrossrefPubMedGoogle Scholar