Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1263-1268
(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1263-1268.)
© 1995 American Heart Association, Inc.
Fibrinogen and Silent Atherosclerosis in Subjects With Cardiovascular Risk Factors
Jaime Levenson;
Philippe Giral;
Mahmoud Razavian;
Jérôme Gariepy;
Alain Simon
From the Centre de Médecine Préventive Cardiovasculaire and
INSERM U28, Broussais Hospital, Paris, France.
Correspondence to Jaime Levenson, MD, INSERM U28, Centre de Médecine Préventive Cardiovasculaire, Hôpital Broussais, 96 rue Didot, 75674 Paris Cedex 14, France.
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Abstract
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Abstract Fibrinogen may play an active role in the
development
and progression of atherosclerotic plaques. We assessed the
association
between fibrinogen levels and atherosclerotic plaques over
three
different arterial sites in an
asymptomatic never-treated male
population with
increased cardiovascular risk. We included 652
men aged
40 to 60 years old with at least one of the following
cardiovascular
risk factors: cholesterol
>6.2 mmol/L and/or systolic blood
pressure
160 mm Hg and/or
diastolic blood pressure
95 mm Hg,
and/or because they
smoked. Carotid and femoral arteries and
the abdominal aorta were
assessed by using ultrasonographic
methods for the presence of plaque,
and subjects were categorized
according to the presence (or absence)
and extent (one versus
two or three sites) of plaque. Plasma fibrinogen
was measured
according to the thrombin-time method of Clauss. While the
presence
of atherosclerosis was significantly related
to age, current
smoking, systolic pressure, LDL
cholesterol, and fibrinogen
levels, the extent of
atherosclerosis was related to age and
triglyceride
and fibrinogen levels. Multiple regression
analysis indicated
independent associations between fibrinogen
and the presence
and extent of atherosclerosis. Plaque
prevalence was significantly
more pronounced with increasing tertile of
fibrinogen levels.
The odds ratio of the upper to lower fibrinogen
tertiles for
the presence of plaque was 1.6 (95% confidence interval,
1.4
to 1.8) and 1.4 (95% confidence interval, 1.2 to 1.7) for its
extent.
Adjustment for other risk factors slightly reduced the
association
between fibrinogen and atherosclerosis. In
conclusion, fibrinogen
levels are related to
atherosclerosis, supporting the hypothesis
that
increased fibrinogen may be one of the mechanisms linking
cardiovascular
risk factors to formation and
progression of plaques.
Key Words: arterial plaques • hypercholesterolemia • hypertension • smoking • fibrin
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Introduction
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The role of elevated fibrinogen levels as
an independent risk
factor for coronary, cerebral, and
peripheral vascular disease
is well established on the
basis of clinical and epidemiological
studies.
1 2 3 4 5 6 7 Strong
evidence implicating high fibrinogen
levels in coronary heart
disease and stroke has been reported
in a meta-analysis of the
cumulative data from six prospective
epidemiological
studies.
8
In cardiovascular disease, fibrinogen has been mainly
considered as being involved in thrombotic occlusion and hence in the
final stage of atherothrombosis. However, a number of investigators
have suggested that fibrinogen may play a more active role in the
development and progression of atherosclerotic plaque. The
simultaneous presence of fibrinogen, its degradation
products, and LDL cholesterol (LDL-C) has been observed
to influence atherogenesis in the arterial
wall.9 10 11 Furthermore, smooth muscle cell proliferation
and migration12 13 stimulated by fibrinogen and fibrin
degradation products suggest that fibrinogen is involved in the
earliest stages of plaque formation. Recent technological progress in
noninvasive arterial investigation techniques based on
high-resolution B-mode ultrasonography has made it possible to detect
atherosclerosis early, before symptoms occur. The
present study examines the association between fibrinogen levels
and the presence and extent of atherosclerotic plaques over three
different arterial sites (carotid and femoral arteries and
the aorta) in an asymptomatic never-treated male
population with increased cardiovascular risk
(hypercholesterolemia, hypertension, and
smoking).
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Methods
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Study subjects were obtained from an ongoing risk
factor–screening
program conducted at the worksite for employees of
several companies
within the Paris, France, area by a group of
occupational health
physicians (PCVMETRA Group: Prévention
Cardiovasculaire
en Médecine du Travail). After their consent was
obtained,
2800 men were referred to the hospital between June 1989 and
January
1993 because they had any of the following characteristics:
hypercholesterolemia
(plasma
cholesterol >6.2 mmol/L [240 mg/L]) and/or hypertension
(systolic
blood pressure
160 mm Hg and/or diastolic
blood pressure
95
mm Hg) at the worksite, and/or because they
smoked. Exclusion
criteria included treatment for hyperlipemia or
hypertension,
secondary hypercholesterolemia or
hypertension, definite hypertriglyceridemia
(>5.6
mmol/L [5 g/L]), renal failure (creatinine >130
µmol/L
[>1.5 mg/dL]), diabetes mellitus (fasting blood glucose
>7.7
mmol/L [>150 mg/dL]), or a history of myocardial infarction,
stroke,
or intermittent claudication. From these subjects, those aged
40
to 60 years were analyzed, resulting in an initial study
sample
of 1752 men. For logistic reasons, complete biological
investigation,
including fibrinogen measurements, could be made only in
a random
subsample of 1230 subjects. The ultrasonic evaluation of the
carotid
and femoral arteries was made in 990 subjects, while those of
the
aorta was made in 730. Only subjects with ultrasonic measurements
on
the three different arterial sites were included,
leading to
a final cross-sectional study sample of 652 men.
Cardiovascular Risk Factor Assessment
Cardiovascular risk indicators were measured
during the morning of a day-hospital visit after 12 hours' fasting.
Total blood cholesterol, HDL cholesterol
(HDL-C) after precipitation of LDL and VLDL by phosphotungstic
acid/magnesium chloride, and plasma triglyceride levels
were measured by using the classic enzymatic method on venous blood
samples that were drawn after the subjects had rested in the supine
position for 10 minutes.14 15 LDL-C was computed from the
Friedewald formula. Citrated platelet-poor plasma was used to
measure plasma fibrinogen according to the thrombin-time method
described by Clauss.16 Brachial systemic blood pressure
was determined as the mean of at least three consecutive measurements
by using the standard sphygmomanometric procedure after the subjects
had rested for at least 10 minutes in the supine position. Smoking was
carefully assessed by questioning the subjects, who were categorized
into current smokers, former smokers, and those who had never smoked.
Body mass index (BMI) (weight/height2) was used to
determine the presence or absence of excess weight.
Arterial Plaque Detection
Studies were performed with real-time B-mode ultrasound imagers
(Radius CF, General Electric, CGR France, and Ultramark 4, Advanced
Technology). Experienced sonographic physicians obtained bilateral
images of the common carotid artery, the carotid bifurcation, the
carotid bulb, and the internal carotid artery, and the common,
superficial, and deep femoral arteries in the upper part of the
thigh14 15 ; the proximal and distal sections of the
abdominal aorta were carefully assessed. Ultrasonic images were
magnified and projected in real time on a television monitor. Hard
copies of real-time images were made for longitudinal and axial
arterial sections. Nonstenotic plaque was
defined as a focal echogenic structure encroaching into the vessel
lumen having a distinct intimal plus medial thickness greater than 50%
thicker than neighboring sites. Intimal plus medial thickness was
evaluated after the sound beam was adjusted perpendicularly to the
arterial surface as the distance from the edge of the first
echogenic bright line, corresponding to the lumen-intima interface, to
the edge of the second echogenic line, corresponding to the
media-adventitia interface.17 Plaque was considered
"present" when one or more arterial plaques were
found regardless of their precise location or number.14 15
Because the aim of the study was to focus on the influence of
fibrinogen on early atherosclerosis, and thrombotic
complications are frequently associated with carotid or femoral artery
stenosis and/or aortic aneurysm, subjects with such
lesions were excluded from the study (n=22). No differences existed
between the two imagers used in this study for plaque detection at each
site examined.
Statistical Analysis
Values are expressed as mean±SD. Comparisons of risk factors
between groups were performed by ANOVA. As the distributions of
fibrinogen and triglyceride values were skewed, a
logarithmic transformation was applied. At each site plaque was
characterized as a dichotomous variable (absent or present),
and the extent of plaque was defined by three classes: one, two, or
three diseased sites (carotid and/or femoral artery and/or abdominal
aorta). Multivariate logistic analysis was
performed to assess the variables independently related to plaque.
A 
2 test was performed to assess trends in
qualitative variables when comparing groups with an increasing
number of diseased sites. The risk of the presence of plaque,
regardless of its site, and the extent of plaque (one diseased site
versus two or three diseased sites) were assessed as a function of
fibrinogen level tertile by using logistic regression analysis.
Association strengths are represented as odds ratios with
95% confidence intervals. Statistical analysis was performed
on an Apple Macintosh computer by using JMP (SAS Institute)
and EXCEL (Microsoft) software.
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Results
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Of this population, 35% had no plaque at any site, while
27%
had carotid plaque, 39% had aortic plaque, and 50% had femoral
plaque.
Plaque was present in one, two, and three sites in 27%,
26%,
and 13% of the population, respectively.
Table 1
shows the cardiovascular risk
characteristics in subjects with and without arterial
plaque. Subjects with arterial plaque were older
(P<.0003) and included a greater number of current smokers
(49% versus 31%, P=.001) and a smaller percentage of
subjects who had never smoked (23% versus 38%, P=.001).
Both groups had a similar percentage of former smokers. Although the
frequency of hypertension was similar in both groups, systolic and
diastolic pressure were slightly higher in subjects with
arterial plaque. Subjects with plaque had higher total and
LDL-C and triglyceride levels and lower HDL-C levels. BMI
and glucose levels did not differ between the two groups. Subjects with
arterial plaque had higher levels of plasma fibrinogen than
those without arterial plaque. The characteristics of
subjects according to the location of arterial plaque are
presented in Table 2. Similar results were
observed between risk factors and plaque locations to those described
in Table 1 between subjects with and without arterial
plaque. Table 3 compares cardiovascular
risk factors between groups with varying extents of silent
atherosclerosis. Subjects with one or two and three
sites of atherosclerosis were comparable regarding BMI,
smoking status, hypertension prevalence, and cholesterol
(total, LDL, and HDL) and glucose levels. In contrast, age and
triglyceride and fibrinogen levels increased with the
number of diseased sites. A multivariate logistic
regression analysis was performed to investigate risk factors
influencing the presence of plaques and the number of diseased sites
(Table 4). Only variables with a significance level
<.10 in univariate analysis were considered.
The presence of arterial plaque was associated with age
(P<.003), current smoking (P<.0001), systolic
pressure (P<.002), and LDL-C (P<.0001) and
fibrinogen (P<.009) levels. The extent of
atherosclerosis was associated with age
(P<.0001) and triglyceride
(P<.0004) and fibrinogen (P<.01) levels.
Plaque prevalences in the lower, middle, and upper thirds of the
fibrinogen level distribution were 55%, 67%, and 74%, respectively
(Fig 1, top). Significant trends were found between
groups with increasing fibrinogen tertile for the presence or absence
of plaque (P<.04). Subjects with plaque belonging to the
lower, middle, and upper thirds of the fibrinogen level distribution
(Fig 1, bottom panel) had one site of arterial plaque in
51%, 42%, and 33% of cases, respectively, two sites in 34%, 40%,
and 42%, respectively, and three sites in 15%, 18%, and 25%,
respectively. Significant trends between groups with increasing
fibrinogen tertile were found for one site (P<.003) and
three sites (P<.04) but not for two diseased sites
(P<.19).
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Figure 1. Bar graphs showing percentage of subjects with and
without plaques (top) and distribution of the extent of plaques
according to fibrinogen tertile (bottom). Tertile cutting points for
fibrinogen are 2.88 and 3.47 g/L.
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The unadjusted odds ratios for the presence of arterial
plaque in the upper versus lower tertiles of plasma fibrinogen level
were 1.6 (95% confidence interval, 1.4 to 1.8) and 1.4 (95%
confidence interval, 1.2 to 1.7) for the extent of arterial
plaque (one site versus two and three sites). Adjustment for
differences in risk factors (age, current smoking, hypertension, LDL-C,
triglycerides) slightly reduced the magnitude of the
associations between fibrinogen and the presence and extent of
atherosclerosis without changing the direction of the
associations. Fig 2 shows the orderly progression of
subjects with arterial plaque with increasing fibrinogen
level according to smoking status. The percentage of subjects with
arterial plaque who had never smoked and were in the lower
fibrinogen tertile differed significantly from that with
arterial plaque who had never smoked and were in the upper
fibrinogen tertile (37% versus 65%; P<.01) and from that
with arterial plaque who were current smokers and in the
lower fibrinogen tertile (37% versus 67%, P<.01).
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Figure 2. Three-dimensional bar graph in which each column
represents the percentage of subjects with
atherosclerosis within each fibrinogen tertile and
according to smoking status. Tertile cutting points for fibrinogen are
2.88 and 3.47 g/L. C indicates current; F, former; N, never; L, lower;
M, middle; and U, upper.
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Discussion
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Our findings in this cross-sectional study of a male population
at
increased risk for cardiovascular disease provide
evidence
that plasma fibrinogen levels are associated with the presence
and
extent of silent atherosclerosis as assessed
noninvasively in
carotid and femoral arteries and the abdominal
aorta.
Subjects with arterial plaque had significantly higher
levels of several well-established cardiovascular risk
factors (age, total cholesterol, LDL-C, and blood pressure)
and were more likely to be current smokers. The
multivariate analysis of the present study
failed to find any significant association between the presence of
arterial plaque and BMI, hypertension prevalence, and
triglyceride and glucose levels. The extent of
atherosclerosis as defined by the number of diseased
sites was significantly higher with increasing age and
triglyceride levels but was not related to BMI, smoking
status, hypertension, or glucose and cholesterol (total,
LDL, and HDL) levels. Thus, the presence of plaque was associated with
LDL-C levels, while the number of diseased sites was associated with
triglyceride levels. LDL-C was significantly associated
with atherosclerotic carotid plaque.14 15 17 18 More
original was the association between the extent of atherosclerotic
plaques and triglycerides levels. In univariate
analysis the mean value of triglycerides was higher
in subjects with than in those without arterial plaque and
in subjects with extended atherosclerosis. However,
multiple analysis showed that only the extent of plaque to two
or three different arterial sites was associated with
triglyceride levels, indicating that this relation was
independent of other variables, in particular HDL-C. The majority
of observational studies demonstrate a significant
univariate relation of triglyceride levels and
coronary heart disease.19 However, there is little
information concerning the relation of triglycerides
with early atherosclerosis. In a prospective 12-year
study on the incidence of coronary heart disease,
triglyceride level was the only risk factor to be an
independent predictor of early onset of disease.20 We have
shown that in asymptomatic
hypercholesterolemic men triglyceride
levels are related to coronary calcification.15
Prolonged exposure of arterial wall cells to
triglycerides may enhance the atherogenic process (as
assessed by wall-thickness imaging).21 These findings
emphasize the importance of evaluating the influence of plasma
triglycerides on the prevalence of early and late
progression of atherosclerosis.
When the effect of these various cardiovascular risk
factors was corrected by multivariate adjustment,
plasma fibrinogen remained a statistically independent predictor of
silent atherosclerosis. Age was the only other factor
independently associated with both the presence and extent of
arterial plaques. While age is known to have a
consistent association with atherosclerotic
lesions,14 15 the role of fibrinogen in early
atherosclerosis is surprisingly less well documented at
the clinical level. Studies have established an association between
fibrinogen and a number of the major cardiovascular
risk factors, including age,6
smoking,4 5 22 23 blood cholesterol and
triglyceride levels,4 5 24 25 26 blood
pressure,27 28 diabetes,5 and lower
socioeconomic status.29 The subjects in the present
study constituted a population of middle-aged male employees selected
on the basis of increased cardiovascular risk, which is
generally associated with high fibrinogen levels. Several prospective
studies have revealed that fibrinogen has a strong predictive power for
coronary heart disease and stroke.2 4 5 6 In these
clinical outcomes, the role of fibrinogen is largely relegated
thrombo-occlusion, the final consequence of
atherosclerosis. Despite known associations between
fibrinogen and other cardiovascular risk factors, few
studies have considered fibrinogen as a factor potentially associated
with the silent phase of atherosclerosis. Most of these
studies use carotid intimal-medial wall thickness as a measure of
atherosclerosis. In a Finnish study the association
between carotid atherosclerosis and fibrinogen was
explained mainly by age and smoking.18 A population-based
study of the community of Bruneck reported that fibrinogen was highly
indicative of carotid artery disease in elderly men and
women.30 The ARIC study group revealed that fibrinogen is
positively associated with asymptomatic early carotid
atherosclerosis.31 A more recent study
found significant association between fibrinogen and intimal-medial
thickness as well as plaque status in the common carotid artery in a
group at high risk for atherosclerotic disease.32 To date,
however, the relation between fibrinogen and the presence and extent of
asymptomatic early atherosclerosis in
other sites than the carotid artery are not well documented in men. In
a highly selected group with peripheral
arterial occlusive disease, fibrinogen was associated with
the severity of atherosclerosis as assessed by the
ankle/brachial pressure index and duplex ultrasonography and/or
angiography.33 An interesting new aspect of our results is
the association of plasma fibrinogen concentration with the different
locations investigated and the extent of
atherosclerosis as defined by the number of diseased
sites.
Additional trends and odds analyses in the present
study strongly suggest that the association between fibrinogen and
early atherosclerosis cannot be attributed to
confounding cardiovascular risk factors and favors the
hypothesis that these silent lesions are partly a direct consequence of
plasma fibrinogen levels. Fibrinogen, fibrin, and LDL-C have been
detected in atherosclerotic plaques, suggesting that a common mechanism
may exist for fibrinogen and lipoprotein entry into the vessel
wall.9 10 11 In addition, other studies have found different
molecular forms of fibrinogen in atherosclerotic
plaques34 35 and a correlation between total
fibrin-related antigens and LDL-C in each group of atherosclerotic
plaques.13 The potential involvement of fibrinogen in the
pathogenesis of atherosclerosis is supported by the
demonstration that fibrinogen degradation products stimulate smooth
muscle proliferation and migration13 and enhance the
release of endothelial cell–derived growth
factors.36
Because silent atherosclerosis was investigated
ultrasonographically in only the carotid and femoral arteries and
abdominal aorta, we do not know whether fibrinogen is similarly
involved in the early development of coronary artery plaque.
However, we have demonstrated that the presence of plaque at two
extracoronary sites has a powerful predictive value for the
presence of coronary calcification.15 It is
probable that high fibrinogen levels are also implicated in
coronary artery atherosclerosis, as
demonstrated in symptomatic patients in whom fibrinogen
increased progressively with the extent of coronary
atherosclerosis.37 38 39
The relation between fibrinogen and smoking should be considered
when interpreting the prevalence of early
atherosclerosis. Cigarette smoking and plasma
fibrinogen concentration have been consistently found to be
associated in the male population.4 5 22 23 Adjustment for
smoking produced little change in the relative odds for silent
atherosclerosis despite the fact that fibrinogen levels
were higher in smokers than nonsmokers. Analysis of the
combined influence of smoking status and fibrinogen on
arterial plaques showed that the percentage of subjects in
the lower fibrinogen tertile with plaques was higher among smokers that
those who had never smoked. In these latter subjects, plaque prevalence
increased with increasing fibrinogen tertile.
Fibrinogen is an acute-phase protein, and thus its high levels could
simply be a reflection of underlying arterial plaque
formation. The advanced lesions of atherosclerosis are
considered the result of an excessive inflammatory fibroproliferative
response to various insults to the arterial wall
endothelium and smooth muscle cells.40
However, genetic control of fibrinogen plasma concentration seems to
exist,41 42 43 and in addition, many other factors (eg,
environmental8 or social29 risk factors for
cardiovascular disease) may increase plasma fibrinogen
levels, which could then play a role in the pathogenesis and course of
arterial disease. High plasma fibrinogen levels may cause a
hypercoagulable state, platelet aggregation, and important
rheological alterations. Red blood cell aggregation and disaggregation
shear stress are profoundly altered by the level of
fibrinogen.28 Enhanced red blood cell aggregability leads
to increased blood viscosity, which in turn might induce a further
slowing of the circulation, which may play a role in the extent of
arterial damage.
In conclusion, this cross-sectional study indicates that
fibrinogen concentration is frequently elevated in subjects with silent
atherosclerosis but particularly in those with several
diseased arterial sites. This supports the hypothesis that
increased fibrinogen may be one of the mechanisms linking
cardiovascular risk factors to the formation and
progression of atherothrombotic lesions.
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Acknowledgments
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The authors are grateful to the staff of the PCVMETRA Group
for
their help: P. Segond (chairman), D. Badet, C. Baylac-Lebot,
A. de
Bonnières, A. Borie, M.R. Bourillon, J. Boursier,
S. Bressler, M.
Bru, M. Chenet, Ph. Corteel, C. Coulange, C.
Delmotte-Devocelle, B.
Demure, M.T. Douguet, M. Dubost, Th.
Drumare, D. Esteve, M. Fragny, O.
Galamand, A.M. Giard, R. Gitel,
C. Guilbert, H. Hafe, F. Kiesgen, E.
Lamothe, C. Lanoiselée,
M.L. Leblanc, N. Le Chevanton, I.
Leprince, A. Marty, D. Miara,
B. Millet, J. Oziel, A. Parini, M.C.
Pasteau, M. Picard, M.M.
Pupponi, C. Quinio, F. Raulet, M.L. Rocca, F.
Szabason, P. Taine,
C. Tarin, A. Touati-Lumbroso, and L. Troudet. We
would also
like to thank Isabelle d'Argentré for secretarial
assistance
and Dr M. Day for help with the English version.
Received January 10, 1995;
accepted May 23, 1995.
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References
|
|---|
-
Meade TW, North WRS, Chakrabarti R, Stirling Y,
Haines AP, Thompson SG. Haemostatic function and
cardiovascular death: early results of a prospective
study. Lancet. 1980;1:1050-1054. [Medline]
[Order article via Infotrieve]
-
Wilhelmsen L, Svardsudd 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;31:501-505.
-
Stone MC, Thorp JM. Plasma fibrinogen: a major
coronary risk factor. J R Coll Gen
Pract. 1985;35:565-569. [Medline]
[Order article via Infotrieve]
-
Meade TW, Mellows S, Brozovic M, Miller GJ,
Chakrabarti RR, North WRS, Haines AP, Sterling Y, Imeson SD, Thompson
SG. Haemostatic function and ischaemic heart disease: principal
results of the Northwick Park Heart Study. Lancet. 1986;2:533-537. [Medline]
[Order article via Infotrieve]
-
Kannel WB, Wolf PA, Castelli WP, D'Agostino RB.
Fibrinogen and risk of cardiovascular disease:
the Framingham Study. JAMA. 1987;258:1183-1186. [Abstract]
-
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 ischaemic heart
disease: the Caerphilly and Speedwell Collaborative Heart Disease
Studies. Circulation. 1991;83:836-844. [Abstract/Free Full Text]
-
Lowe GDO, Fowkes FGR, Dawes J, Donnan PT, Lennie SE,
Housley E. Blood viscosity, fibrinogen, and activation of
coagulation and leukocytes in peripheral
arterial disease and the normal population in the Edinburgh
artery study. Circulation. 1993;87:1915-1920. [Abstract/Free Full Text]
-
Ernst E, Resch KL. Fibrinogen as a
cardiovascular risk factor: a meta-analysis and
review of the literature. Ann Int Med. 1993;118:956-963. [Abstract/Free Full Text]
-
Sadoshima S, Tanaka E. Fibrinogen and low
density lipoprotein in the development of cerebral
atherosclerosis.
Atherosclerosis. 1979;34:93-103.[Medline]
[Order article via Infotrieve]
-
Smith EB, Alexander KM, Massie IB. Insoluble
`fibrin' in human aortic intima: quantitative studies on the
relationship between insoluble `fibrin,' soluble fibrinogen and
low
density lipoprotein.
Atherosclerosis. 1976;23:19-39. [Medline]
[Order article via Infotrieve]
-
Smith EB, Staples EM, Dietz HS, Smith RH. Role
of endothelium in sequestration of lipoprotein and
fibrinogen in aortic lesions, thrombi, and graft
pseudo-intimas. Lancet. 1979;2:812-816. [Medline]
[Order article via Infotrieve]
-
Thompson WD, Smith EB.
Atherosclerosis and the coagulation
system. J Pathol. 1989;159:97-106. [Medline]
[Order article via Infotrieve]
-
Smith EB, Keen GA, Grant A, Stirk C. Fate of
fibrinogen in human arterial intima.
Arteriosclerosis. 1990;10:263-275. [Abstract/Free Full Text]
-
Giral P, Pithois-Merli I, Filitti V, Levenson J,
Plainfosse MC, Mainardi C, Simon A, and the PCVMETRA Group. Risk
factors and early extracoronary atherosclerotic plaques
detected by three-site ultrasound imaging in
hypercholesterolemic men. Arch Int
Med. 1991;151:950-956. [Abstract]
-
Megnien JL, Sene V, Jeannin S, Hernigou A,
Plainfosse MC, Merli I, Atger V, Moatti N, Levenson J, Simon A, and the
PCVMETRA Group. Coronary calcification and its relation
to extracoronary atherosclerosis in
asymptomatic hypercholesterolemic
men. Circulation. 1992;85:1799-1807. [Abstract/Free Full Text]
-
Clauss A. Gerinnungsphysiologische
Schnellmethode zur Bestimmung des Fibrinogens. Acta
Haematol. 1957;17:231-237.
-
Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R.
Intimal plus medial thickness of the arterial wall:
a direct measurement with ultrasound imaging.
Circulation. 1986;74:1399-1406. [Abstract/Free Full Text]
-
Salonen R, Seppanen K, Rauramaa R, Salonen JK.
Prevalence of carotid atherosclerosis and serum
cholesterol in Eastern Finland.
Arteriosclerosis. 1988;8:788-792. [Abstract/Free Full Text]
-
Austin M. Plasma triglyceride and
coronary heart disease. Arterioscler
Thromb. 1991;11:2-14. [Abstract/Free Full Text]
-
Benfante RJ, Reed DM, Maclean CJ, Yano K. Risk
factors in middle age that predict early and late onset of
coronary heart disease. J Clin
Epidemiol. 1989;42:95-104. [Medline]
[Order article via Infotrieve]
-
Ryu JE, Howard G, Craven TE, Bond MG, Hagaman AP,
Crouse JR. Postprandial triglyceridemia and carotid
atherosclerosis in middle-aged subjects.
Stroke. 1992;23:823-828. [Abstract/Free Full Text]
-
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;31:968-988.
-
Bonithon-Kopp C, Levenson J, Scarabin PY, Guillanneuf
MT, Kirzin JM, Malmejac A, Guize L. Longitudinal associations
between plasma viscosity and cardiovascular risk
factors in a middle-aged French population.
Atherosclerosis. 1993;104:173-182. [Medline]
[Order article via Infotrieve]
-
Balleisen L, Bailey J, Epping PH, Schulte H, Van De Loo
J. 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 Haemost. 1985;52:475-479.
-
Lowe GDO, Drummond MM, Third JLHC, Bremner WF, Forbes
CD, Prentice CRM, Lawerie TDV. Increased plasma fibrinogen and
platelet aggregates in type II hyperlipoproteinaemia.
Thromb Haemost. 1979;42:1503-1507.
-
Levenson J, Del Pino M, Razavian M, Merli I, Filitti V,
Simon A. Hypercholesterolaemia alters
arterial and blood factors related to
atherosclerosis in hypertension.
Atherosclerosis. 1992;95:171-179. [Medline]
[Order article via Infotrieve]
-
Letcher RL, Chien S, Pickering TG, Sealey JE, Laragh
JH. Direct relationship between blood pressure and blood
viscosity in normal and hypertensive subjects: role of fibrinogen and
concentration. Am J Med. 1981;70:1195-1202. [Medline]
[Order article via Infotrieve]
-
Razavian M, Del Pino M, Simon A, Levenson J.
Increase in erythrocyte disaggregation shear stress in
hypertension. Hypertension. 1992;20:247-252. [Abstract/Free Full Text]
-
Markowe HL, Marmot MG, Shipley MJ, Bulpitt CJ, Meade
TW, Stirling Y, Vickers MV, Semmence A. Fibrinogen: a possible
link between social class and coronary heart disease.
BMJ. 1985;291:1312-1314.
-
Willeit J, Kiechl S. Prevalence and risk factors
of asymptomatic extracranial carotid artery
atherosclerosis. Arterioscler
Thromb. 1993;13:661-668. [Abstract/Free Full Text]
-
Folsom AR, Wu KK, Shahar E, Davis CE (ARIC).
Association of hemostatic variables with prevalent
cardiovascular disease and asymptomatic
carotid artery atherosclerosis.
Arterioscler Thromb. 1993;13:1829-1836. [Abstract/Free Full Text]
-
Agewall S, Wikstrand J, Suurkula M, Tengborn L,
Fagerberg B. Carotid artery wall morphology, haemostatic factors
and cardiovascular disease: an ultrasound study in men
at high and low risk for atherosclerotic disease. Blood
Coagul Fibrinolysis. 1994;5:895-904. [Medline]
[Order article via Infotrieve]
-
Lassila R, Peltonen S, Lepantalo M, Saarinen O,
Kauhanen P, Manninen V. Severity of peripheral
atherosclerosis is associated with fibrinogen and
degradation of cross-linked fibrin.
Arterioscler Thromb. 1993;13:1738-1742. [Abstract/Free Full Text]
-
Bini A, Fenoglio JJ Jr, Sobel J, Owel J, Fejgl M,
Kaplan KL. Immunochemical characterization of fibrinogen, fibrin
I and fibrin II in human thrombi and atherosclerosis
lesions. Blood. 1987;69:1038-1045. [Abstract/Free Full Text]
-
Bini A, Fenoglio JJ Jr, Mesa-Tejada R, Kudryk BJ,
Kaplan KL. Identification and distribution of fibrinogen,
fibrin, and fibrin(ogen) degradation products in
atherosclerosis: use of monoclonal antibodies.
Arteriosclerosis. 1989;9:109-121. [Abstract/Free Full Text]
-
Lorenzet R, Sobel JH, Bini A, Witte LD. Low
molecular weight fibrinogen degradation products stimulate the
release of growth factors from endothelial
cells. Thromb Haemost. 1992;68:357-363. [Medline]
[Order article via Infotrieve]
-
Lowe GD, Drummond MM, Lorimer AR, Hutton I, Forbes CD,
Prentice CR, Barbenel JC. Relation between extent of
coronary artery disease and blood viscosity.
BMJ. 1980;1:673-674.
-
Handa K, Kono S, Saku K, Sasaki J, Kawano T, Sasaki Y.
Plasma fibrinogen levels as an independent indication of
severity of coronary atherosclerosis.
Atherosclerosis. 1989;77:209-213. [Medline]
[Order article via Infotrieve]
-
Broadhurst P, Kelleher C, Hughes L, Imeson JD, Raftery
ED. Fibrinogen, factor VII clotting activity and
coronary artery disease severity.
Atherosclerosis. 1990;85:169-173. [Medline]
[Order article via Infotrieve]
-
Ross R. The pathogenesis of
atherosclerosis: a perspective for the 1990s.
Nature. 1993;362:801-809. [Medline]
[Order article via Infotrieve]
-
Hamsten A, Iselius L, De Faire U, Blomback M.
Genetic and cultural inheritance of plasma fibrinogen
concentration. Lancet. 1987;2:988-991. [Medline]
[Order article via Infotrieve]
-
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;1:1452-1455. [Medline]
[Order article via Infotrieve]
-
Lee AJ, Lowe GDO, 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;69:338-342.[Abstract/Free Full Text]
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Abstract
Introduction