Ischaemic heart disease and stroke are the major causes of death in the Western world. Established risk factors such as smoking, hypertension and hypercholesterolemia explain only some of these events. Most myocardial infarctions and cardiac deaths are precipitated by acute occluding coronary thrombi, and it has been known for some time that thrombosis participates in atherogenesis. For these reasons, haemostatic variables have been included in studies of cardiovascular risk. The plasma fibrinogen level is associated with both the severity and the extent of coronary, cerebral and peripheral atherosclerosis. In prospective studies, fibrinogen was found to be an independent predictor of myocardial infarction in both sexes and of stroke in men. The plasma fibrinogen level thus provides information on risk over and above that supplied by established risk factors. Fibrinogen may play a part in atherothrombosis via several mechanisms: (1) by promoting atherosclerosis, (2) as an essential component of platelet aggregation, (3) because the amount of fibrin deposited and the size of the clot are directly related to the plasma fibrinogen level and (4) because fibrinogen increases plasma viscosity. Nevertheless, it is not yet possible to determine whether high fibrinogen levels are a cause or a consequence of cardiovascular disease because no drugs that selectively lower plasma fibrinogen levels are available. In addition, further standardization of measurements is needed before routinely including plasma fibrinogen in cardiovascular risk scores.
HellerRFChinnSTunstall-PedoeHDRoseG: How well can we predict coronary heart disease? Findings in the United Kingdom Heart Disease Prevention ProjectBMJ1984, 288:1409–1411. Thisstudy reports that age, blood pressure, cholesterol concentration and smoking habits overlap substantially between people who have and have not suffered myocardial infarction.
2.
RokitanskyC: A Manual of Pathological Anatomy. London: Sydenham Society; 1852. Thefirst report of the possible role of fibrin in atherogenesis.
3.
DuguidJB: Thrombosis as a factor in the pathogenesis of coronary atherosclerosisJ Pathol Bacteriol1946, 58:207–212. Thispaper revived and confirmed Rokitansky's early observations [2].
4.
DeWoodMSporesJNotskeRMouserLTBurroughsRGoldenMS: Prevalence of total coronary occlusion during the early hours of transmural myocardial infarctionN Engl J Med1980, 303:897–902. Coronaryarteriography was used to show that coronary occlusion by thrombosis is frequent during the early hours of transmural infarction.
5.
DaviesMJWoolfNRobertsonWB: Pathology of acute myocardial infarction with particular reference to occlusive coronary thrombiBr Heart J1976, 38:659–664. Thisstudy and that by Davies and Thomas [6] found occluding coronary thrombi in most cases of myocardial infarction and sudden cardiac death.
6.
DaviesMJThomasA: Thrombosis and acute coronary artery lesions in sudden cardiac ischemic deathN Engl J Med1984, 310:1137–1140. Seecomment on Davies et al. [5].
7.
SchwartzCJ: Thrombosis in the pathogenesis of sudden cardiac death and myocardial infarction In Prostaglandins and the Cardiovascular System. Edited by OatesJA.New York: Raven Press; 1981:1–14. Areview of the pathological basis of myocardial infarction and sudden cardiac death that places particular emphasis on the role of thrombosis.
8.
SherrySMarderVJ: Thrombosis, fibrinolysis and thrombolytic therapy: A perspectiveProg Cardiovasc Dis1991, 34:89–100.
9.
SeifriedERijkenDCHoegeeETanswellPKluftCNieuwenhuizenW: Fibrinogen degradation products – FbDPs – appear in blood of healthy volunteers upon infusion of recombinant tissue type plasminogen activator (rt-PA) In Fibrinogen 2: Biochemistry, Physiology and Clinical Relevance. Edited by LoweGDODouglasJTForbesCDHenschenA.Amsterdam: Excerpta Medica; 1987:289–292.
10.
CookNSUbbenD: Fibrinogen as a major risk factor in cardiovascular diseaseTrends Pharmacol Sci1990, 11:444–451. Acomprehensive review of the biochemistry, bioregulation and therapeutic modulation of fibrinogen, of the platelet fibrinogen receptor glycoprotein IIb/IIIa and of fibrinogen as a cardiovascular risk factor.
11.
BalleisenLBaileyJEppingP-HSchulteHvan 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 menopauseThromb Haemost1985, 54:475–479. Thisstudy and those of Folsom et al. [12], Krobot et al. [13], Lee et al. [14] and Folsom et al. [15] describe the association between plasma fibrinogen levels and putative cardiovascular risk factors in Western populations.
12.
FolsomARQamhiehHTFlackJMHilnerJELiuKHowardBV: Plasma fibrinogen: Levels and correlates in young adultsAm J Epidemiol1993, 138:1023–1036. Seecomment on Balleisen et al. [11].
13.
KrobotKHenseHWCremerPEberleEKeilU: Determinants of plasma fibrinogen: Relation to body weight, waist-to-hip ratio, smoking, alcohol, age and sex. Results from the second MONICA Augsburg survey, 1989–1990Arterioscler Thromb1992, 12:780–788. Seecomment on Balleisen et al. [11].
14.
LeeAJSmithWCSLoweGDOTunstall-PedoeH: Plasma fibrinogen and coronary risk factors: The Scottish Heart Health StudyJ Clin Epidemiol1990, 43:913–919. Seecomment on Balleisen et al. [11].
15.
FolsomARWuKKConlanMG: Fibrinogen and cardiovascular risk in the Atherosclerosis Risk in Communities (ARIC) study In Fibrinogen: A ‘New’ Cardiovascular Risk Factor. Edited by ErnstEKoenigWLoweGDOMeadeTW.Vienna: Blackwell-MZV; 1992:124–129. Seecomment on Balleisen et al. [11].
16.
LeeAJLoweGDOSmithWCSTunstall-PedoeH: Plasma fibrinogen in women: Relation with oral contraception, the menopause and hormone replacement therapyBr J Haematol1993, 83:616–621. Thispaper and that by Meilahn et al. [17] describe the effect of endogenous and exogenous hormones on plasma fibrinogen.
17.
MeilahnENKullerLHMatthewsKAKissJE: Variation in plasma fibrinogen levels by menopausal status and use of hormone replacement therapy: The Healthy Women study. Fibrinogen: A ‘New’ Cardiovascular Risk Factor. Edited by ErnstEKoenigWLoweGDOMeadeTW.Vienna: Blackwell-MZV; 1992:338–343. Seecomment on Lee et al. [16].
18.
Van der MoorenMJDemackerPNThomasCMBormGFRollandR: A 2-year study on the beneficial effects of 17 betaoestradiol-dydrogesterone therapy on serum lipoproteins and Lp(a) in postmenopausal women: No additional unfavourable effects of dydrogesteroneEur J Obstet Gynecol Reprod Biol1993, 52:117–123.
19.
JohanssonJOLandinKTengbornLRosenTBengtssonBA: High fibrinogen and plasminogen activator inhibitor activity in growth hormone-deficient adultsArterioscler Thromb1994, 14:434–437. Thisstudy showed a considerable difference in plasma fibrinogen levels (0.8 g/l) between growth hormone-deficient adults and healthy controls, although the number of patients investigated was small (n = 20).
20.
KannelWBD'AgostinoRBBelangerAJ: Fibrinogen, cigarette smoking, and risk of cardiovascular disease: Insights from the Framingham StudyAm Heart J1987, 113:1006–1010. Areport from the Framingham Study on the net and joint effect of cigarette smoking and fibrinogen on the occurrence of cardiovascular disease.
21.
MeadeTWImesonJStirlingY: Effects of changes in smoking and other characteristics on clotting factors and the risk of ischemic heart disease, Lancet1987, ii:986–988. Thesedata from the Northwick Park Heart Study showed higher fibrinogen levels in smokers than in non-smokers. A lifetime duration of smoking was a significant determinant of fibrinogen concentration. After the discontinuation of smoking, 5 years or more were needed before plasma fibrinogen levels returned to those of people who had never smoked.
22.
EliassonMLundbladDEvrinP-EAsplundK: Smoking, but not use of tobacco, is associated with elevated plasma fibrinogen levels. The Northern Sweden MONICA studyBlood Coagul Fibrinolysis1994, 5 (suppl 2):7–8.
23.
BalleisenLAssmannGBaileyJEppingP-HSchulteHvan 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 fractionsThromb Haemost1985, 54:721–723.
24.
LoweGDODrummondMMThirdJLHCBremerWFForbesCDPrenticeCRM: Increased plasma fibrinogen and platelet aggregates in type II hyperlipoproteinemiaThromb Haemost1980, 42:1503–1507.
25.
JayRHRamplaingMWBetteridgeDJ: Abnormalities of blood rheology in familial hypercholesterolaemia: Effects of treatmentAtherosclerosis1990, 85:249–256.
26.
SimpsonHCRMannJIMeadeTWChakrabartiRStirlingYWoolfL: Hypertriglyceridaemia and hypercoagulabilityLancet1983, i:786–790.
27.
DiMinnoGSilverMJCerboneAMRainoneAPostiglioneAManciniM: Increased fibrinogen binding to platelets from patients with familial hypercholesterolemiaArteriosclerosis1986, 6:203–211. Despitethe low number of patients with familial hypercholesterolaemia (n = 9), it was shown that their platelets bound significantly more fibrinogen than those of controls even after using aspirin and an ADP scavenger.
28.
ConnellyJBCooperJAMeadeTW: Strenuous exercise and plasma fibrinogenBr Heart J1992, 67:351–354. Thisstudy in a large male population showed that strenuous exercise was associated with lower plasma fibrinogen levels, which explains in part the beneficial effect of physical exercise and provides a valuable tool to reduce risk.
29.
GandaOPArkinCF: Hyperfibrinogenemia: A major determinant of vascular complications in diabetes In Fibrinogen: A ‘New’ Cardiovascular Risk Factor. Edited by ErnstEKoenigWLoweGDOMeadeTW.Vienna: Blackwell-MZV; 1992:254–258. Vascularcomplications in patients with diabetes mellitus correlated best with fibrinogen level, hypertension and the duration of disease in a multiple regression model taking 13 other factors into account.
30.
MaclureM: Demonstration of deductive meta-analysis: Ethanol intake and risk of myocardial infarctionEpidemiologic Reviews1993, 15:328–351.
31.
MollerLKristensenTS: Plasma fibrinogen and ischemic heart disease risk factorsArterioscler Thromb1991, 11:344–350. Socialclass was shown to be the variable most strongly associated with plasma fibrinogen levels after multivariate analysis.
32.
JernCErikssonETengbornLRisbergBWadenvikHJernS: Changes of plasma coagulation and fibrinolysis in response to mental stressThromb Haemost1989, 62:767–771. Short-time mental stress in young men was found to increase plasma fibrinogen levels significantly. Knowledge of fibrinogen's long-term effects on cardiovascular risk would be more conclusive, but standardization is more difficult.
33.
RosengrenAWilhelmsenLWelinLTsipogianniATeger-NilssonAWedelH: Social influences and cardiovascular risk factors as determinants of plasma fibrinogen concentration in a general population sample of middle-aged menBMJ1990, 300:634–638. Socialclass was not related to fibrinogen levels in a multiple regression analysis, in contrast to the study by Moller and Kristensen [31].
34.
StoutRWCrawfordV: Seasonal variations in fibrinogen concentrations among elderly peopleLancet1991, 338:9–13. Sixty-eight participants aged 75 years and over had a remarkable increase of 23% in fibrinogen concentrations in the coldest 6 months of the year, a finding that is in keeping with the higher cardiovascular morbidity and mortality seen in winter.
35.
Van der BomJGBotsMLGrobbeeDE: Seasonal variations of plasma fibrinogen and leucocytes are dissociated in the Rotterdam study [abstract]Blood Coagul Fibrinolysis1994, 5 (suppl 2):8.
IsoHFolsomARWuKKFinchAMungerRGSatoS: Hemostatic variables in Japanese and Caucasian menAm J Epidemiol1989, 130:925–934. Arural and an urban population in Japan had the lowest fibrinogen level compared with Japanese people living in America (about 10% higher) and with white Americans (30% higher; only non-smokers compared). This is in keeping with the low incidence of myocardial infarction in Japan and suggests that the fibrinogen concentration is regulated by both environmental and genetic factors.
38.
MeadeTW: Fibrinogen and other clotting factors in cardiovascular disease In Atherosclerotic Cardiovascular Disease, Hemostasis, and Endothelial Function. Edited by FrancisRBJr.New York: Marcel Dekker; 1992:1–34.
39.
HamstenAIseliusLDe FaireUBlombäckM: Genetic and cultural inheritance of plasma fibrinogen concentrationLancet1987, ii:988–991. Bymeans of path analysis in 85 families with members who suffered early myocardial infarction and in 85 randomly selected families, 51% of the variance in plasma fibrinogen levels could be explained by genetic heritability, whereas the cultural heritability was negligible.
40.
ReedTTracyRPFabsitzRR: Minimal genetic influences on plasma fibrinogen level in adult males in the NHLBI twin studyClin Genet1994, 45:71–77. Thisreport on a minimal genetic influence on fibrinogen levels in twins with a mean age of 63 years contrasts the findings of Hamsten et al. [39].
41.
HumphriesSECookMDubowitzMStirlingYMeadeTW: Role of genetic variations at the fibrinogen locus in determination of plasma fibrinogen concentrationsLancet1987, i:1452–1455. Polymorphismsat alpha- and beta-fibrinogen loci were found to account for 15% of the variance in plasma fibrinogen levels in 91 healthy British individuals.
42.
BergKKierulfP: DNA polymorphisms at fibrinogen loci and plasma fibrinogen concentrationClin Genet1989, 36:229–235. Theauthors could not confirm the British results in 118 Norwegian subjects.
43.
ConnorJMFowkesFGRWoodJSmithFBDonnanPTLoweGDO: Genetic variation at fibrinogen loci and plasma fibrinogen levelsJ Med Genet1992, 29:480–482. Nosignificant associations were found between four DNA polymorphisms at alpha-, beta- and gamma-fibrinogen loci and plasma fibrinogen levels in 247 participants from a Scottish study on peripheral artery disease.
44.
FowkesFGRConnorJMSmithFBWoodJDonnanPTLoweGDO: Fibrinogen genotype and risk of peripheral atherosclerosisLancet1992, 339:693–696. Onehundred and twenty-one patients had significantly higher frequencies of an allele at the beta-fibrinogen locus (Bcll cutting site) than healthy controls.
45.
HeinrichJFunkeHRustSSchulteHSchönfeldRKöhlerE: Impact of polymorphisms in the alpha- and beta-fibrinogen gene on plasma fibrinogen concentrations in coronary heart disease patientsThromb Res1995, 77:209–215.
46.
LosnerSVolkBWWilenskyND: Fibrinogen concentration in acute myocardial infarctionArch Intern Med1954, 93:231–238.
47.
McDonaldLEdgillM: Coagulability of the blood in ischaemic heart disease, Lancet1957, ii:457–460.
48.
HamstenABlombäckMWimanBSvenssonJSzamosiADe FaireU: Haemostatic function in myocardial infarctionBr Heart J1986, 55:58–66.
49.
HandaKKonoSSakuKSasakiJKawanoTSasakiY: Plasma fibrinogen levels as an independent indicator of severity of coronary atherosclerosisAtherosclerosis1989, 77:209–213.
50.
BolibarIKienastJThompsonSGMatthiasRNiessnerHFechtrupC: Relation of fibrinogen to presence and severity of coronary artery disease is independent of other coexisting heart diseaseAm Heart J1993, 125:1601–1605.
51.
BroadhurstPKelleherCHughesLImesonJDRafteryEB: Fibrinogen, factor VII clotting activity and coronary artery disease severityAtherosclerosis1990, 85:169–173.
52.
ECAT Angina Pectoris study group: ECAT Angina Pectoris study: Baseline associations of haemostatic factors with extent of coronary arteriosclerosis and other coronary risk factors in 3000 patients with angina pectoris undergoing coronary angiographyEur Heart J1993, 14:8–17.
53.
ThompsonSGKienastJPykeSDMHaverkateFvan de LooJCW: Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. Principal results of the ECAT Angina Pectoris studyN Engl J Med1995, 332:635–641. Thisis a very carefully designed multicentre study that investigated the role of haemostasis in the progression of coronary heart disease. The mean difference in fibrinogen level between angina pectoris patients with and without stenoses on coronary angiography was 0.28 g/l. During the 2-year follow-up in 3043 patients, 106 coronary events were documented; these were related to fibrinogen concentrations at entry. The risk increased by three times from the lowest to the highest quintile of the fibrinogen distribution. In patients with low fibrinogen levels, the risk remained low regardless of the total cholesterol level.
54.
BurrMLHollidayRMFehilyAMWhiteheadPJ: Haematological prognostic indices after myocardial infarction: Evidence from the Diet and Reinfarction Trial (DART)Eur Heart J1992, 13:166–170. Thefibrinogen concentration in patients after myocardial infarction was positively associated with all-cause mortality. The lower mortality in patients who gave up smoking appeared to be mediated by fibrinogen levels.
55.
MartinJFBathPMWBurrML: Influence of platelet size on outcome after myocardial infarctionLancet1991, 338:1409–1411. Thispaper mainly deals with the larger mean platelet volumes in patients with myocardial infarction who had a further ischaemic event during the 2-year follow-up; fibrinogen levels also predicted re-infarction, however.
56.
HeinrichJSchulteHSchönfeldRKöhlerEAssmannG: Study of coagulation, fibrinolysis and acute-phase reaction in coronary heart disease patients with atherosclerosis in the coronary and peripheral arteries and those arteries supplying the brainThromb Haemost1995, 73:374–379.
57.
SmithEBThompsonWD: Fibrin as a factor in atherogenesisThromb Res1994, 73:1–19. Thisis a detailed review of the role of fibrinogen, fibrin and their derived fragments in the initiation of atherosclerosis and in the growth and expansion of atherosclerotic plaques.
58.
GrottaJCYatsuTMPettigrewLCRhoadesHBratinaPVitalD: Prediction of carotid stenosis progression by lipid and hematologic measurementsNeurology1989, 39:1325–1331. Thisstudy in patients with carotid atherosclerosis showed that a combination of coronary artery disease, high LDL cholesterol levels and high plasma fibrinogen levels predicted the progression of carotid stenosis.
59.
SzirmaiIGKamondiAMagyarHJuhaszC: Relation of laboratory and clinical variables to the grade of carotid atherosclerosisStroke1993, 24:1811–1816. In232 stroke patients, a high fibrinogen level and low HDL cholesterol level were strongly associated with the presence of severe carotid atherosclerosis.
60.
TohgiHKawashimaMTamuraKSuzukiH: Coagulationfibrinolysis abnormalities in acute and chronic phases of cerebral thrombosis and embolismStroke1990, 21:1663–1667. Patientswith cerebral thrombosis had elevated levels of fibrinogen and fibrinopeptide A during the acute, subacute and chronic phases of cerebral thrombosis and embolism.
61.
CoullBMBeamerNde GarmoPSextonGNordtFKnoxR: Chronic hyperviscosity in subjects with acute stroke, transient ischemic attack, and risk factors for strokeStroke1991, 22:162–168. Bloodviscosity was higher in patients with acute stroke than in those with transient ischaemic attacks and in individuals at risk of stroke. This increased viscosity was associated with increased plasma fibrinogen levels.
62.
ErnstEMatraiAMarshallM: Blood rheology in patients with transient ischemic attacksStroke1988, 19:634–636.
63.
LoweGDOFowkesFGRDawesJDonnanPTLennieSEHousleyE: Blood viscosity, fibrinogen and activation of coagulation and leucocytes in peripheral arterial disease and the normal population in the Edinburgh Artery studyCirculation1993, 87:1915–1920. Aftermultivariate analysis, fibrinogen levels and blood viscosity were associated with peripheral artery narrowing.
64.
DormandyJHoareEColleyJArrowsmithDEDormandyTL: Clinical, haemodynamic, rheological and biochemical findings in 126 patients with intermittent claudicationBMJ1973, 4:576–581.
65.
WisemanSKenchingtonGDainRMarshallCEMcCollumCNGreenhalghRM: Influence of smoking and plasma factors on patency of femoropopliteal vein graftsBMJ1989, 299:643–646. In157 patients with saphenous vein femoropopliteal bypass grafts, the fibrinogen level was the best predictor of graft occlusion during the first year after bypass.
66.
BanerjeeAKPearsonJGillilandELGossDLewisJDStirlingY: A six year prospective study of fibrinogen and other risk factors associated with mortality in stable claudicantsThromb Haemost1992, 68:261–263. Of333 patients with stable intermittent claudication, 114 died within the 6-year follow-up period; an increase in fibrinogen level of 1 g/l was associated with a twofold increase in the probability of death within the subsequent 6 years.
67.
MeadeTWNorthWRChakrabartiRStirlingYHainesPThompsonSG: Haemostatic function and cardiovascular death: Early results of a prospective studyLancet1980, i:1050–1054. Thisis the first prospective study to show that the plasma fibrinogen level (and factor VIIc) was higher in men who died from cardiovascular disease (n = 27) than in those who survived. The independent association between the fibrinogen level and cardiovascular disease was at least as strong as the relationship with the total cholesterol level.
68.
MeadeTWBrozovicMChakrabartiRRHainesAPImesonJDMellowsS: Haemostatic function and ischaemic heart disease: Principal results of the Northwick Park Heart StudyLancet1986, ii:533–537. Theearly results of the Northwick Park Heart Study were confirmed by this evaluation of 109 ischaemic events, especially for events occuring within 5 years of entry. An elevation of the plasma fibrinogen level of one standard deviation increased by 84% the risk of an ischaemic heart disease event within the subsequent 5 years. The effect was more pronounced in younger men.
69.
YarnellJGWBakerIASweetnamPMBaintonDO'BrienJRWhiteheadPJ: Fibrinogen, viscosity and white blood cell count are risk factors for ischemic heart diseaseCirculation1991, 83:836–844. Inthis prospective study, a large number of 251 ischaemic events were observed. Fibrinogen, plasma viscosity and leucocyte count could replace total cholesterol, diastolic blood pressure and body mass index in a logistic regression model (also taking into account age and smoking) without a loss of predictivity.
70.
StoneMCThorpJM: Plasma fibrinogen: A major coronary risk factorJ R Coll Gen Pract1985, 35:565–569. Thiswas one of the first prospective studies to include the measurement of fibrinogen. However, the sample of men followed up was small and was highly selected (40 ischaemic events).
71.
HeinrichJBalleisenLSchulteHAssmannGvan de LooJ: Fibrinogen and factor VII in the prediction of coronary risk. Results from the PROCAM Study in healthy menArterioscler Thromb1994, 14:54–59 (Correction 1994, 14:1392). Thisstudy includes the measurement of levels of total, HDL and LDL cholesterol, triglycerides, fibrinogen and factor VIIc as well as established coronary risk factors. Sixty-five per cent of all coronary events (n = 82) occurred in the highest quintile of the multiple logistic function. Since more than 10 000 men and women with fibrinogen data were included, more data will be available in the near future, especially that concerning the coronary risk of fibrinogen in women.
72.
CremerPNagelDBöttcherBSeidelD: Fibrinogen: A coronary risk factor [in German]Diagnose Labor1992, 42:28–35. Althoughthese data were not published in an international scientific journal, they provided new information on the relationship between fibrinogen and lipids, especially LDL cholesterol and lipoprotein (a), in men aged 40–60 years (107 ischaemic events).
73.
KannelWBWolfPACastelliWPd'AgostinoRB: Fibrinogen and risk of cardiovascular disease: The Framingham StudyJAMA1987, 258:1183–1186. Thisis the only prospective study of fibrinogen as a cardiovascular risk factor to report on a large number of events in both men and women (cardiovascular events in 165 men and 147 women; 92 strokes and 214 ischaemic coronary events). The risk of coronary heart disease was significantly related to the fibrinogen level in both sexes. The risk of stroke increased with fibrinogen level only in men. The impact of fibrinogen was comparable to that of established major coronary risk factors.
74.
WilhelmsenLSvärdsuddKKorsan-BengtsenKLarssonBWelinLTibblinG: Fibrinogen as a risk factor for stroke and myocardial infarctionN Engl J Med1984, 311:501–505. Thisprospective study showed a significant association between the fibrinogen level at entry and myocardial infarction (n = 92) and stroke (n = 37) after univariate analysis and with stroke alone after multivariate analysis. There was an impressive increase in the risk of stroke in men who had both high fibrinogen levels and high systolic blood pressures.
75.
ErikssonHKorsan-BengtsenKWelinLSvärdsuddKLarssonBTibblinGWilhelmsenL: 21-year follow-up of CHD and total mortality among men born in 1913 In Fibrinogen: A ‘New’ Cardiovascular Risk Factor. Edited by ErnstEKoenigWLoweGDOMeadeTW.Vienna: Blackwell-MZV; 1992:115–119. This21-year follow-up (125 ischaemic coronary events, 47 strokes, 33 ischaemic coronary events and strokes) of the above-mentioned study [74] confirmed the earlier findings but found an association between fibrinogen and stroke after the multivariate analysis only if smoking was excluded.
76.
ErnstEReschKL: Fibrinogen as a cardiovascular risk factor: A meta-analysis and review of the literatureAnn Intern Med1993, 118:956–963. Thisis a comprehensive meta-analysis covering 92147 person-years documented in the prospective studies listed above [67–69, 71–74]. It confirms that the plasma fibrinogen level is an independent marker of cardiovascular risk and discusses whether the requirements for a causal relationship are fulfilled.
77.
SmithEBKeenAGrantAStirkC: Fate of fibrinogen in human arterial intimaArteriosclerosis1990, 10:263–275. Inthis and the study by Bini et al. [78], the content of fibrinogen, fibrin and their fragments in normal and atherosclerotic vessels and mural thrombi was analysed, leading to the suggestion that an increase in fibrin formation and degradation is associated with the progression of atherosclerotic disease.
78.
BiniAFenoglioJJMesa-TejadaRKudrykBKaplanKL: Identification and distribution of fibrinogen, fibrin and fibrin(ogen) degradation products. Use of monoclonal antibodiesArteriosclerosis1989, 9:109–121. Seecomment on Smith et al. [77].
79.
KoenigWHombachVErnstESundMMrazWKeilU: Plasma viscosity as a cardiovascular risk factor [letter]Circulation1992, 86:1045.
80.
PeerschkeEIZuckerMBGrantRAEganJJJohnsonMM: Correlation between fibrinogen binding to human platelets and platelet aggregabilityBlood1980, 55:841–847.
81.
TripMDCatsVMvan CapelleFJLVreekenJ: Platelet hyper-reactivity and prognosis in survivors of myocardial infarctionN Engl J Med1990, 322:1549–1554. Spontaneousplatelet aggregation in survivors of myocardial infarction was found to predict new events during 5-year follow-up.
82.
ElwoodPCRenaudSSharpDSBeswickADO'BrienJRYarnellJWG: Ischemic heart disease and platelet aggregation. The Caerphilly Collaborative Heart Disease studyCirculation1991, 83:38–44. Asignificant positive relationship was found between the occurrence of of ischaemic events and ADP-induced platelet aggregation in this study of patients with myocardial infarction.
83.
ThaulowEErikssenJSandvikLStormorkenHCohnPF: Blood platelet count and function are related to total and cardiovascular death in apparently healthy menCirculation1991, 84:613–617. Themortality associated with ischaemic heart disease in men who were healthy at entry was significantly higher in the highest quartile of platelet count and in the 50% of men with more rapid ADP-induced platelet aggregation.
84.
ChooiCCGallusAS: Acute-phase reaction, fibrinogen level and thrombus sizeThromb Res1989, 53:493–501.
85.
BlombäckBBlombäckMCarlssonKFatahKHamstenAHesselB: Fibrin gel structure in health and disease In Fibrinogen: A ‘New’ Cardiovascular Risk Factor. Edited by ErnstEKoenigWLoweGDOMeadeTW.Vienna: Blackwell-MZV; 1992:11–18. Usingliquid permeation, turbidity and confocal three-dimensional microscopy of fibrin gels, the authors showed that the fibrinogen concentration has an effect on the structure of the fibrin gel.
86.
BlombäckB: Fibrinogen structure, activation, polymerization and fibrin gel structureThromb Res1994, 75:327–328.
