Expression of a Paternal History of Premature Myocardial Infarction on Fibrinogen, Factor VIIC and PAI-1 in European Offspring - The EARS Study

Summary

To assess the role of genetic and environmental factors in the predisposition to atherosclerosis, 682 students whose father had suffered a myocardial infarction before the age of 55 (“cases”) and 1312 controls matched for age and sex, were recruited from 14 Universities in Europe. Fibrinogen, factor Vile and PAI-1 were compared between cases and controls across European regions. Fibrinogen and factor Vile were positively correlated with BMI, smoking and contraception. PAI-1 was positively and independently correlated with BMI and waist-to-hip ratio, and negatively with contraception. Factor Vile and PAI-1 were correlated with cholesterol and triglycerides, and fibrinogen was weakly correlated with LDL-cholesterol. After adjustment for covariates and lipids, fibrinogen level was significantly higher in male cases than in controls (2.38 vs 2.29, p <0.01). No such difference was found in females (2.59 vs 2.57 - NS). There was no significant case/control difference for factor Vile and PAI-1. These results support the hypothesis that fibrinogen is a transmissible risk factor of coronary artery disease in males. No such evidence was provided for factor Vile and PAI-1.

• References

• 1 Meade TW, North WRS, Chakrabarti R, Stirling Y, Haines AP, Thompson SG. Haemostatic function and eardio vascular death: early results of a prospective study. Lancet 1980; i: 1050-4
• 2 Meade TW, Mellows S, Brozovic M, Miller GJ, Chakrabarti RR, Nuitli 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; ii: 533-7
• 3 Wilhemsen L, Svardsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibbiin G. Fibrinogen as a risk factor for stroke and myocardial mtarction. N Engl J Med 1984; 311: 501-5
• 4 Kannel WB, Wolf PA, Castelli WP, D'Agostino RB. Fibrinogen and risk of cardiovascular disease - The Framingham Study. JAMA 1987; 258: 1183-6
• 5 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 diseases. The Caerphilly and Speedwell Collaborative Heart Disease Studies. Circulation 1991; 83: 836-44
• 6 Stone MC, Thorp JM. Plasma fibrinogen - a major coronary risk factor. J R Coll Gen Pract 1985; 35: 565-9
• 7 Hamsten A, Wiman B, De Faire U, Blomback M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. NEngl J Med 1985; 313: 1557-63
• 8 Paramo J, Colucci M, Collen D. Plasminogen activator inhibitor in the blood of patients with coronary artery disease. BMJ 1985; 291: 573-4
• 9 Olofsson BO, Dahlen G, Nilsson TK. Evidence for increased levels of plasminogen activator inhibitor in plasma of patients and tissue plasminogen activator in plasma of patients with angiographically verified coronary artery disease. European Heart J 1989; 10: 77-82
• 10 Hamsten A, De Faire U, Walldius G, Dahlen G, Szamosi A, Landou C, Blomback M, Wiman B. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 1987; ii: 3-9
• 11 EARS group. EARS: European Atherosclerosis Research Study – Design and objectives. Int J Epidemia (in press).
• 12 Kluft C, Verheijen JH. Leiden fibrinolysis working party: blood collection and handling procedures for assessment of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1). Fibrinolysis 1990; 4 Supp (02) 155-61
• 13 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237
• 14 Scarabin PY, Van Dreden P, Bonithon-Kop C, Orssaud G, Bara L, Conard J, Samama M. Age-related changes in factor VII activation in healthy women. Clin Science 1988; 75: 341-3
• 15 Eriksson E, Ranby M, Gyzander E, Risberg B. Determination of plasminogen inhibitor in plasma using t-PA and a chromogenic single-point poly-d- lysine stimulated assay. Thromb Res 1988; 50: 91-101
• 16 Balleisen L, Bailey I, Epping PH, Schulte H, Van de Loo J. Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population -1. Baseline data on the relation to age, gender, body weight, smoking, alcohol, pill-using, and menopause. Thromb Haemost 1985; 54: 475-9
• 17 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
• 18 Krobot K, Hense HW, Cremer P, Eberle E, Keil U. Determinants of plasma fibrinogen: Relation to body weight, waist-to-hip ratio, smoking, alcohol, age and sex - Results from the second MONICA Augsburg Survey, 1989-1990. Arterioscl Thromb 1992; 12: 780-8
• 19 Sundell IB, Nilsson TK, Ranby M, Hallmans G, Hellsten G. Fibrinolytic variables are related to age, sex, blood pressure and body build measurements: a cross-sectional study in Norsjo, Sweden. J Clin Epidem 1989; 42: 719-23
• 20 Meade TW, North WRS, Chakrabarti R, Haines AP, Stirling Y. Population based distribution of haemostatic variables. Br Med Bull 1977; 33: 283-8
• 21 Lee AJ, Smith WCS, Lowe GDO, Tunstall-Pedoe H. Plasma fibrinogen and coronary risk factors: the Scottish Heart Health Study. J Clin Epidemiol 1990; 43: 913-9
• 22 Meade TW, Imeson J, Stirling Y. Effects of changes in smoking and other characteristics on clotting factors and the risk of ischaemic heart disease. Lancet 1987; 986-8
• 23 Plu-Bureau G, Scarabin PY, Bara L, Malmejac A, Guize L, Samama M. Factor VII activation and oral contraceptives. Thromb Res 1993; 70: 275-80
• 24 Jespersen J, Kluft C. Inhibition of tissue-type plasminogen activator in plasma of women using oral contraceptives and in normal women during a menstrual cycle. Thromb Haemost 1986; 55: 388-9
• 25 Jespersen J, Petersen KR, Skouby SO. Effects of newer oral contraceptives on the inhibition of coagulation and fibrinolysis in relation to dosage and type of steroid. Am J Obstet Gynecol 1990; 163: 396-403
• 26 Siegbahn A, Ruusuvaara L. Age dependence of blood fibrinolytic components and the effects of low-dose oral contraceptives on coagulation and fibrinolysis in teenagers. Thromb Haemost 1988; 60: 361-4
• 27 Juhan-Vague I, Alessi MC, Joly P, Thirion X, Vague P, Declerck PJ, Serradimigni A, Collen D. Plasma plasminogen activator inhibitor-1 in angina pectoris. Influence of plasma insulin and acute phase response. Arteriosclerosis 1989; 9: 362-7
• 28 Oseroff A, Krishnamurti C, Hassett A, Tang D, Alving B. Plasminogen activator and plasminogen activator inhibitor activities in men with coronary artery disease. J Lab Clin Med 1989; 113: 88-93
• 29 Mehta J, Mehta P, Lawson D, Saldeen T. Plasma tissue plasminogen activator inhibitor levels in coronary artery disease: correlation with age and serum triglyceride concentrations. J Am Coll Cardiol 1987; 9: 263-8
• 30 Balleisen L, Assmann G, Bailey J, Epping PH, Schulte H, Van de Loo J. 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 Haemost 1985; 54: 721-3
• 31 Miller GJ, Walter SJ, Stirling Y, Thompson SG, Esnouf MP, Meade TW. Assay of factor VII activity by two techniques: evidence for increased conversion of VII to aVII_a in hyperlipidemia, with possible implications for ischaemic heart disease. Br J Haematol 1985; 59: 249-58
• 32 Scarabin PY, Bara L, Samama M, Orssaud G. Further evidence that activated factor VII is related to plasma lipids. Br J Haematol 1985; 61: 186-7
• 33 Scarabin PY, Bara L, Ricard S, Poirier O, Cambou JP, Arveiler D, Luc G, Evans AE, Samama MM, Cambien F. Genetic variation at the (β-fibrinogen locus in relation to plasma fibrinogen concentrations and risk of myocardial infarction - The ECTIM Study. Arterioscl Thromb 1993; 13: 886-91
• 34 Hamsten A, Iselius D, De Faire U, Blomback M. Genetic and cultural inheritance of plasma fibrinogen concentration. Lancet 1987; ii: 988-90
• 35 Humphries SE, Cook M, Dubowitz M, Stirling Y, Meade TW. Role of genetic variation at the fibrinogen locus in determination of plasma fibrinogen concentrations. Lancet 1987; i: 1452-5
• 36 Thomas AE, Green FR, Kelleher CH, Wilkes HC, Brennan PJ, Meade TW, Humphries SE. Variation in the promoter region of the β fibrinogen gene is associated with plasma fibrinogen levels in smokers and non-smokers. Thromb Haemost 1991; 65: 487-90
• 37 Fowkes FGR, Connor JM, Smith FB, Wood J, Donnan PT, Lowe GDO. Fibrinogen genotype and risk of peripheral atherosclerosis. Lancet 1992; 339: 693-6
• 38 Humphries S, Ye S, Talmud P. European Artherosclerosis Research Study: genotype at the fibrinogen locus (G-₄₅₃-A β-gene) is associated with differences in plasma fibrinogen levels in young men and women from different regions in Europe: Evidence for gender - genotype - environment interaction (submitted).
• 39 Rosseneu M, Fruchart JC, Bard JM, Nicaud V, Vinaimont N, Cambien F. On behalf of the EARS group. Plasma apolipoprotein concentrations in young adults with a parental history of premature coronary heart disease and in controls: The EARS Study. Circulation (in press).
• 40 Isles CG, Hole DJ, Hawthorne VM, Lever AF. Relation between coronary risk and coronary mortality in women of the Renfrew and Paisley Survey: a comparison with men. Lancet 1992; 339: 702-6
• 41 Fey GH, Fuller GM. Regulation of acute phase gene expression by inflammatory mediators. Mol Biol Med 1987; 4: 323-38
• 42 Huber P, Laurent M, Dalmon J. Human (β fibrinogen gene expression: upstream sequences involved in its tissue specific expression and its dexamethasone and interleukin 6 stimulation. J Biol Chem 1990; 265: 5695-701
• 43 Poli V, Cortese R. Interleukin 6 induces a liver specific nuclear protein that binds to the promoters of acute phase genes. Proc Natl Acad Sci USA 1989; 86: 8202-6
• 44 Prentice CRM. Thrombosis: a common arrival point of different pathways. In: Thrombosis - an update. Scientific Press; Florence Italy: 1992: 25-45
• 45 Hoffman CJ, Miller RH, Lawson WE, Hultin MB. Elevation of factor VII activity and mass in young adults at risk of ischemic heart disease. I Am Coll Cardiol 1989; 14: 941-6
• 46 Hoffman CJ, Burns P, Lawson WE, Katz JP, Miller R, Hultin MB. Plasma fibrinogen level is not elevated in young adults from families with premature ischemic heart disease. Arterioscl Thromb 1993; 13: 800-3
• 47 Green F, Kelleher C, Wilkes H, Temple A, Meade T, Humphries S. A common genetic polymorphism associated with lower coagulation factor VII levels in healthy individuals. Arterioscl Thromb 1991; 11: 540-6
• 48 Tiret L, Nicaud V, Ehnholm C, Havekes L, Menzel HJ, Ducimetiere P, Cambien F. Inference of the strength of genotype-disease association from studies comparing offspring with and without parental history of disease. Ann Hum Genet 1993; 57: 141-9
• 49 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 Vile, factor VIIIc and Von Willebrand factor and their relations to cardiovascular disease risk factors. Am J Epidem 1989; 130: 925-34
• 50 Miller GJ, Martin JC, Webster J, Wilkes H, Miller NE, Wilkinson WH, Meade TW. Association between dietary fat intake and plasma factor VII coagulant activity - a predictor of cardiovascular mortality. Atherosclerosis 1986; 60: 269-77
• 51 Dawson S, Hamsten A, Wirnan B, Hennev A, Humphries S. Genetic variation at the plasminogen activator inhibitor-1 locus is associated with altered levels of plasma plasminogen activator inhibitor-1 activity. Arterioscl Throm 1991; 11: 183-90
• 52 Kooistra T, Bosma JP, Tons HAM, Berg AP, Meyer P, Princen HMG. Plasminogen activator inhibitor 1: biosynthesis and mRNA level are increased by insulin in cultured human hepatocytes. Thromb Haemost 1989; 62: 723-8
• 53 Stiko-Rahm A, Wiman B, Hamsten A, Nilsson I. Secretion of plasminogen activator inhibitor 1 from cultured human umbilical vein endothelial cells is induced by very low density lipoproteins. Arteriosclerosis 1990; 10: 1067-72
• 54 Ridker PM, Vaughan DE, Stampfer MJ, Manson JE, Hennekens CH. Endogenous tissue-type plasminogen activator and risk of myocardial infarction. Lancet 1993; 341: 1165-8
• 55 Thompson SG, Kienast J, Pyke SDM, Haverkate F, Van de Loo JCW. on behalf of the ECAT Angina Pectoris Study Group Hemostatic factors and the risk of developing new coronary events in patients with angina pectoris - Principal results of the ECAT Angina Pectoris Study (in press).