Download PDF
Thromb Haemost 1999; 82(03): 1106-1111
DOI: 10.1055/s-0037-1614337
Letters to the Editor
Schattauer GmbH

Gender Differences in the Relation between Fibrinogen, Tissue-type Plasminogen Activator Antigen and Markers of Insulin Resistance: Effects of Smoking

Louise I. Mennen
1   From the INSERM, Unit 258, and the Faculty of Medicine Paris- Sud, Villejuif, France
,
Beverley Balkau
1   From the INSERM, Unit 258, and the Faculty of Medicine Paris- Sud, Villejuif, France
,
Marie-Aline Charles
1   From the INSERM, Unit 258, and the Faculty of Medicine Paris- Sud, Villejuif, France
,
Alain D’Hour
2   Centre d’Examens de Santé, Le Mans, France
,
Jean-Michel le Mauff
3   Centre d’examens de Santé, Blois, France
› Author Affiliations the D.E.S.I.R. Study Group
Further Information

Publication History

Received 29 January 1999

Accepted after revision 21 April 1999

Publication Date:
09 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

A stronger positive association between fibrinogen or tissue-type plasminogen activator antigen (tPA-ag) and fasting insulin is observed in women than in men. We investigated whether this effect could be explained by a difference in smoking habits.

The relations between markers for insulin resistance [fasting insulin and insulin resistance as estimated by the homeostasis model assessment (HOMA-IR)] and fibrinogen and tPA-ag were examined cross-sectionaly in 4976 (582 for tPA-ag) subjects from the D.E.S.I.R. (Data from an Epidemiological Study on the Insulin Resistance syndrome) study. The modifying effect of smoking habits were evaluated.

Seventeen percent of women and 27% of men were smokers. Fibrinogen concentrations were higher in smokers than in non-smokers, in men only. Female smokers had lower concentrations of tPA-ag than non-smokers. In both women and men, fibrinogen was positively associated with fasting insulin [women: β = 0.33 mg/U (95% confidence interval: 0.29, 0.37); men: β = 0.15 mg/U (0.11, 0.19)] and with HOMA-IR [women: β= 0.17 μg/μU mol/l (0.15, 0.19); men: β = 0.06 (0.04, 0.08)]. For tPA-ag these associations were for insulin β = 0.76 mg/U (0.54, 0.98) and β = 0.89 mg/U (0.67, 1.11), and for HOMA-IR β = 0.47 μg/μU mol/l (0.33, 0.61) and β = 0.45 μg/μU mol/l (0.33, 0.57), women and men respectively. The associations of fibrinogen and tPA-ag with insulin and HOMA-IR were sharply reduced in male smokers compared to male non-smokers, however the strength of the associations in male non-smokers did not reach that in women.

Fibrinogen and tPA-ag are independetly related with markers of insulin resistance, with the relation with fibrinogen being stronger in women than in men. The strong modifying effect of smoking habits does not completely explain this gender difference.

 

  • References

  • 1 Meade TW, Brozovic M, Chakrabarti RR, Haines AP, Imeson JD, Mellows S, Miller GJ, North WRS, Stirling Y, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; 6: 533-7.
    PubMedGoogle Scholar
  • 2 Cortellaro M, Boschetti C, Cofrancesco E, Zanussi C, Catalano M, de Gaetano G, Gabrielli L, Lombardi B, Specchia G, Tavazzi L, Tremoli E, della Volpe A, Polli E. The PLAT study: hemostatic function in relation to atherothrombotic ischemic events in vascular disease patients. Principal results. Arterioscler Thromb 1992; 12: 1063-70.
    CrossrefPubMedGoogle Scholar
  • 3 Yarnell JWG, Baker IA, Sweetnam PM, Bainton D, O’Brien JR, Whitehead PJ, Elwood PC. Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease. The Carphilly and Speedwell Collaborative Heart Disease studies. Circulation 1991; 83: 836-44.
    CrossrefPubMedGoogle Scholar
  • 4 Hamsten A, de Faire U, Walldius G, Dahlen G, Szamosi A, Landou C, Blombäck M, Wiman B. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 1987; ii: 3-9.
    PubMedGoogle Scholar
  • 5 Wilhelmsen L, Svärdsudd K, Korsan-Bengsten K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984; 311: 501-5.
    CrossrefPubMedGoogle Scholar
  • 6 Stone MC, Thorp JM. Plasma fibrinogen: a major coronary risk factor. J R Coll Gen Pract 1985; 35: 565-9.
    PubMedGoogle Scholar
  • 7 Kannel WB, Wolf PA, Castelli WP, D’Agostino RB. Fibrinogen and risk of cardiovascular disease: the Framingham Study. JAMA 1987; 9: 1183-6.
    PubMedGoogle Scholar
  • 8 Rånby M, N’guyen G, Scarabin PY, Samama M. Immunoreactivity of tissue plasminogen activator and of its inhibitor complexes. Thromb Haemost 1989; 61: 409-14.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo JCW. for the European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Hemostatic factors and risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995; 332: 635-41.
    CrossrefPubMedGoogle Scholar
  • 10 Smith FB, Lee AJ, Fowkes FGR, Price JF, Rumley A, Lowe GDO. Hemostatic factors as predictors of ischaemic heart disease and stroke in the Edinburgh Artery Study. Arterioscler Thromb Vasc Biol 1997; 17: 3321-5.
    CrossrefPubMedGoogle Scholar
  • 11 Jansson JH, Olofsson BO, Nilsson TK. Predictive value of tissue plasminogen activator mass concentration on long term mortality in patients with coronary artery disease. A 7-year follow up. Circulation 1993; 88: 2030-4.
    CrossrefPubMedGoogle Scholar
  • 12 Ridker PM, Vaughan DE, Stampfer MJ, Manson JE, Hennekens CH. Endogenous tissue-type plasminogen and risk of myocardial infarction. Lancet 1993; 341: 1165-8.
    CrossrefPubMedGoogle Scholar
  • 13 Eliasson M, Evrin PE, Lundblad D. Fibrinogen and fibrinolytic variables in relation to anthropometry, lipids and blood pressure. The Northern Sweden MONICA Study. J Clin Epidemiol 1994; 47: 513-24.
    CrossrefPubMedGoogle Scholar
  • 14 DeFronzo RA, Ferrannini E. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991; 14: 173-94.
    CrossrefPubMedGoogle Scholar
  • 15 Folsom AR, Wu KK, Davis CE, Conlan MG, Sorlie PD, Szklo M. Population correlates of plasma fibrinogen and factor VII, putative cardiovascular risk factors. Atherosclerosis 1991; 91: 191-205.
    CrossrefPubMedGoogle Scholar
  • 16 Reaven GM. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-607.
    CrossrefPubMedGoogle Scholar
  • 17 Reaven GM. The role of insulin resistance and hyperinsulinemia in coronary heart disease. Metabolism 1992; 41 (Suppl. 01) 16-9.
    CrossrefPubMedGoogle Scholar
  • 18 Donahue RP, Bean JA, DeCarlo Donahue R, Goldberg RB, Prineas RJ. Does insulin resistance unite the separate components of the insulin resistance syndrome? Evidence from the Miami Community health study. Arterioscler Thromb Vasc Biol 1997; 17: 2413-7.
    CrossrefPubMedGoogle Scholar
  • 19 Juhan-Vague I, Thompson SG, Jespersen J. ECAT Angina Pectoris Study Group. Involvement of the hemostatic system in the insulin resistance syndrome. A study of 1500 patients with angina pectoris. Arterioscler Thromb 1993; 13: 1865-73.
    CrossrefPubMedGoogle Scholar
  • 20 Lindahl B, Asplund K, Eliasson M, Evrin PE. Insulin resistance syndrome and fibrinolytic activity: the Northern Sweden MONICA Study. Int J Epidemiol 1996; 25: 291-9.
    CrossrefPubMedGoogle Scholar
  • 21 Hughes K, Aw TC, Kuperan P, Choo M. Central obesity, insulin resistance, syndrome X, lipoprotein(a), and cardiovascular risk in Indians, Malays, and Chinese in Singapore. J Epidemiol Community Health 1997; 51: 394-9.
    CrossrefPubMedGoogle Scholar
  • 22 Feskens EJM, Kromhout D. Hyperinsulinemia, risk factors, and coronary heart disease. The Zutphen Elderly Study. Arterioscler Thromb 1994; 14: 1641-7.
    CrossrefPubMedGoogle Scholar
  • 23 Cigolini M, Targher G, de Sandre G, Muggeo M, Seidell JC. Plasma fibrinogen in relation to serum insulin, smoking habits and adipose tissue fatty acids in healthy men. Eur J Clin Invest 1994; 24: 126-30.
    CrossrefPubMedGoogle Scholar
  • 24 Eliasson M, Roder ME, Dinesen B, Evrin PE, Lindahl B. Proinsulin, intact insulin, and fibrinolytic variables and fibrinogen in healthy subjects. Diabetes Care 1997; 20: 1252-5.
    CrossrefPubMedGoogle Scholar
  • 25 Mansfield MW, Heywood DM, Grant PJ. Circulating levels of factor VII, fibrinogen, and von Willebrand factor and features of insulin resistance in first-degree relatives of patients with NIDDM. Circulation 1996; 94: 2171-6.
    CrossrefPubMedGoogle Scholar
  • 26 De Pergola G, De Mitrio V, Giogino F, Sciaraffia M, Minnena A, Di Bari L, Pannacciulli N, Giorgino R. Increase in both pro-thrombotic and anti-thrombotic factors in obese premenopausal women: relationship with body fat distribution. Int J Obesity 1997; 21: 527-35.
    CrossrefPubMedGoogle Scholar
  • 27 Vague P, Juhan-Vague I, Aillaud MF, Badier C, Viard R, Alessi MC, Collen D. Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level, and relative body weight in normal and obese subjects. Metabolism 1986; 35: 250-3.
    CrossrefPubMedGoogle Scholar
  • 28 Nabulsi AA, Folsom AR, Heiss G, Weir SS, Chambless LE, Watson RL, Eckfeldt JH. Fasting hyperinsulinemia and cardiovascular disease risk factors in non diabetic adults: stronger associations in lean versus obese subjects. Atherosclerosis Risk in Communities Study Investigators. Metabolism 1995; 44: 914-22.
    CrossrefPubMedGoogle Scholar
  • 29 Meade TW, Imeson J, Stirly Y. Effects of changes in smoking and other characteristics on clotting factors and risk of ischaemic heart disease. Lancet 1987; ii: 986-8.
    PubMedGoogle Scholar
  • 30 The D.E.S.I.R. Study Group. An epidemiologic survey from a network of French Health Examination Centres. D.E.S.I.R. (Epidemiologic Data on the Insulin Resistance Syndrome). Rev Epidem Santé Publ 1996; 4: 373-5.
    PubMedGoogle Scholar
  • 31 Wojta J, Turcu L, Wagner OF, Korninger C, Binder BR. Evaluation of fibrinolytic capacity by a combined assay system for tissue type plasminogen activator antigen and function using monoclonal anti-tissue-type plasminogen activator antibodies. J Lab Clin Med 1987; 109: 665-71.
    PubMedGoogle Scholar
  • 32 Couderc R, Legrand A. Bilan lipidique en pratique medical courante. Biologiste et Practicien; France: vol 105 1996
    Google Scholar
  • 33 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-9.
    CrossrefPubMedGoogle Scholar
  • 34 Facchini FS, Hollebeck C, Jeppesen J, Chen YDI, Reaven GM. Insulin resistance and cigarette smoking. Lancet 1992; 339: 1128-30.
    CrossrefPubMedGoogle Scholar
  • 35 Eliasson B, Attvall S, Taskinen MR, Smith U. The insulin resistance syndrome in smokers is related to smoking habits. Arterioscler Thromb 1994; 14: 1946-50.
    CrossrefPubMedGoogle Scholar
  • 36 Mooy JM, Grootenhuis PA, de Vries H, Bouter LM, Kostense PJ, Heine RJ. Determinants of specific serum insulin concentrations in a general Caucasian population aged 50-74 years (the Hoorn Study). Diab Med 1998; 15: 45-52.
    CrossrefPubMedGoogle Scholar
  • 37 Eliasson B, Attvall S, Taskinen MR, Smith U. Smoking cessation improves insulin sensitivity in healthy middle-aged men. Eur J Clin Invest 1997; 27: 450-6.
    CrossrefPubMedGoogle Scholar
  • 38 Geppert A, Graf S, Beckmann R, Hornykewycz S, Schuster E, Binder BR, Huber K. Concentration of endogenous tPA antigen in coronary artery disease. Arterioscler Thromb Vasc Biol 1998; 18: 1634-42.
    CrossrefPubMedGoogle Scholar
  • 39 Simpson AJ, Booth NA, Moore NR, Gray RS. Does chronic smoking influence fibrinolytic potential in type 1 diabetes mellitus?. Diab Med 1998; 15: 683-7 34.
    CrossrefPubMedGoogle Scholar
  • 40 Imperatore G, Riccardi G, Iovine C, Rivellese AA, Vaccaro O. Plasma fibrinogen: a new factor of the metabolic syndrome. Diabetes Care 1998; 21: 649-54.
    CrossrefPubMedGoogle Scholar
  • 41 Kario K, Matsuo T, Kobayashi H, Sakata T, Miyata T, Shimada K. Gender differences of disturbed hemostasis related to fasting insulin level in healthy very elderly Japanese aged >75 years. Atherosclerosis 1995; 116: 211-9.
    CrossrefPubMedGoogle Scholar
  • 42 Kario K, Nago N, Kayaba K, Saegusa T, Matsuo H, Goto T, Tsutsumi A, Ishikawa S, Kuroda T, Miyamoto T, Matsuo T, Shimada K. Characteristics of the insulin resistance syndrome in a Japanese population. The Jichi Medical School Cohort Study. Arterioscler Thromb Vasc Biol 1996; 16: 269-74.
    CrossrefPubMedGoogle Scholar
  • 43 Mohamed-Ali V, Gould MM, Gillies S, Goubet S, Yudkin JS, Haines AP. Association of proinsulin-like molecules with lipids and fibrinogen in non-diabetic subjects – evidence against a modulating role for insulin. Diabetologia 1995; 38: 1110-6.
    CrossrefPubMedGoogle Scholar
  • 44 Burchfiel CM, Curb JD, Sharp DS, Rodriguez BL, Arakaki R, Chyou PH, Yano K. Distribution and correlates of insulin in elderly men. The Honolulu Heart Program. Arterioscler Thromb Vasc Biol 1995; 15: 2213-21.
    CrossrefPubMedGoogle Scholar
  • 45 Båvenholm P, Proudler A, Silveira A, Crook D, Blombäck M, de Faire U, Hamsten A. Relationships of insulin and intact and split proinsulin to haemostatic function in young men with and without coronary artery disease. Thromb Haemost 1995; 73: 568-75.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 46 Stefanick ML, Legault C, Tracy RP, Howard G, Kessler CM, Lucas DL, Bush TL. Distribution and correlates of plasma fibrinogen in middle-aged women. Initial findings of the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study. Arterioscler Thromb Vasc Biol 1995; 15: 2085-93.
    CrossrefPubMedGoogle Scholar
  • 47 Ishikawa S, Kario K, Nago N, Kayaba K, Hiraoka J, Matsuo H, Goto T, Miyamoto T, Tsutsumi A, Nakamura Y, Shimada K, Inoue K, Igarashi M. Factor VII and fibrinogen levels examined by age, sex, and other atherosclerotic risk factors in a Japanese population. The Jichi Medical School Cohort Study. Thromb Haemost 1997; 77: 890-3.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Hughes K, Choo M, Kuperan P, Ong CN, Aw TC. Cardiovascular risk factors in non-insulin-dependent diabetics compared to non-diabetic controls: a population-based survey among Asians in Singapore. Atherosclerosis 1998; 136: 25-31.
    CrossrefPubMedGoogle Scholar
  • 49 Attvall S, Fowelin J, Lager I, van Schenck H, Smith U. Smoking induces insulin resistance. A potential link with the insulin resistance syndrome. J Intern Med 1993; 233: 327-32.
    CrossrefPubMedGoogle Scholar
  • 50 Meilahn EN, Cauley JA, Tracy RP, Macy EO, Gutai JP, Kuller LH. Association of sex hormones and adiposity with plasma levels of fibrinogen and PAI-I in postmenopausal women. Am J Epidemiol 1996; 143: 159-66.
    CrossrefPubMedGoogle Scholar
  • 51 Folsom AR, Qamhieh HT, Wing RR, Jeffery RW, Stinson VL, Kuller LH, Wu KK. Impact of weight loss on plasminogen activator inhibitor (PAI-1), factor VII, and other hemostatic factors in moderately overweight adults. Arterioscler Thromb 1993; 13: 162-9.
    CrossrefPubMedGoogle Scholar
  • 52 Henry M, Tregouët DA, Alessi MC, Aillaud MF, Visvikis S, Siest G, Tiret L, Juhan-Vague I. Metabolic determinants are much more important than genetic polymorphisms in determining the PAI-1 activity and antigen plasma concentrations. A family study with part of the Stanislas Cohort. Arterioscler Thromb Vasc Biol 1998; 18: 84-91.
    CrossrefPubMedGoogle Scholar
  • 53 Pickart L. Fat metabolism, the fibrinogen/fibrinolytic system and blood flow: new potentials for the pharmacological treatment of coronary heart disease. Pharmacology 1981; 23: 271-80.
    CrossrefPubMedGoogle Scholar
  • 54 McCarty MF. Hemostatic concomitants of syndrome X. Med Hypoth 1995; 44: 179-93.
    CrossrefPubMedGoogle Scholar
  • 55 Pickart LR, Thaler MM. Free fatty acids and albumin as mediators of thrombin-stimulated fibrinogen synthesis. Am J Physiol 1976; 230: 996-1002.
    PubMedGoogle Scholar
  • 56 Pandolfi A, Iacoviello L, Capani F, Vitacolonna E, Donati MB, Consoli A. Glucose and insulin independently reduce the fibrinolytic potential of human vascular smooth muscle cells in culture. Diabetologia 1996; 39: 1425-31.
    CrossrefPubMedGoogle Scholar