From the Department of Clinical Epidemiology, Department of Cardiology,
Hemostasis and Thrombosis Research Center, Leiden University Hospital,
Netherlands.
Correspondence to Prof Dr Frits R. Rosendaal, Department of Clinical Epidemiology, Leiden University Hospital, Bldg 1:CO-P, PO Box 9600, 2300 RC Leiden, Netherlands. E-mail rosendaal{at}rullf2.medfac.leidenuniv.nl
Methods and Results—Among 560 men with a first myocardial
infarction before the age of 70 years, 1.8% were heterozygous carriers
of the 20210 variant of the prothrombin gene. The control group
consisted of 646 men who were frequency matched by age. In the latter
group, the frequency of the 20210 AG genotype was 1.2%. The
risk of myocardial infarction in the presence of the AG
genotype was increased by 50% (odds ratio, 1.5; 95%
confidence interval [95% CI], 0.6 to 3.8). The risk of myocardial
infarction for carriership of factor V Leiden mutation was increased by
40% (odds ratio, 1.4; 95% CI, 0.8 to 2.2). When a coagulation defect
was present (ie, the 20210 AG prothrombin genotype or the
factor V Leiden mutation), the risk of myocardial infarction for
carriers versus noncarriers was 1.4 (95% CI, 0.9 to 2.2). This risk
was substantially increased when one of the major
cardiovascular risk factors of smoking, hypertension,
diabetes mellitus, or obesity also was present, with odds ratios
varying between 3 and 6. These risks exceeded those of the single
effects of the cardiovascular risk factors (ie, in the
absence of the coagulation defect).
Conclusions—We conclude that in men the 20210 G
In only one study has the relation been studied of the prothrombin
variant (20210 G
In men, the association of the prothrombin 20210 G
Cases consisted of men with a first myocardial infarction before the
age of 70 years who were hospitalized in a university or general
hospital in Leiden, the Netherlands, between January 1990 and January
1996. Two of the three characteristics of typical chest pain, a
transient rise in cardiac enzymes to more than twice the upper limit,
and ECG changes typical for myocardial infarction had to be present
in the discharge report or hospital record of a patient with
myocardial infarction. The study protocol was approved by the ethics
committees of both hospitals.
Control subjects also were men, who were frequency matched to the
patients (cases) by 10-year age groups, had undergone an orthopedic
intervention between January 1990 and May 1996, and had received
prophylactic anticoagulants for a short period after the
intervention. The orthopedic intervention varied from a plaster cast
for a ruptured hamstring to hip replacement. The control subjects were
identified in the records of the Leiden Anticoagulant Clinic; they
did not have a history of myocardial infarction and had not received
anticoagulants for
Both patients and control subjects were born in the Netherlands and
were living in the Leiden region. Excluded were men with renal disease
(n=10), severe (neuro)psychiatric problems (n=28), or a life expectancy
of <1 year (n=16). The response among the remaining patients and
control subjects was 84.3% (560) and 77% (646), respectively.
All persons completed a questionnaire concerning the presence of
cardiovascular risk factors such as smoking habits and
alcohol consumption. For patients, all questions referred to the period
before the myocardial infarction. The quetelet index was derived by
dividing weight (kg) by squared height (m2).
Persons were considered obese if their quetelet index exceeded 30
kg/m2. Medication use and history of diabetes
were determined through an interview with control subjects and
retrieved from discharge letters for the patients. A person was
classified as hypertensive or hypercholesterolemic when
he was taking prescription drugs for these conditions. The
variables of obesity, diabetes, hypertension, and
hypercholesterolemia were grouped together as
"metabolic risk factors."3
Blood Collection and Laboratory Analysis
The status of the prothrombin variant (20210 G
Heterozygous or homozygous carriership of the prothrombin 20210A
allele or heterozygous or homozygous carriership of factor V Leiden
mutation was defined as a "coagulation defect."
Statistical Analysis
Prothrombin 20210A and Factor V Leiden Mutation
The relative risk of myocardial infarction in the presence of factor V
Leiden mutation was 1.4 (95% CI, 0.8 to 2.2) (Table 2
Coagulation Defect
Coagulation Defect and Interaction
In a population-based case-control study among women aged 18 to 44
years, the risk of myocardial infarction associated with carriership of
prothrombin 20210A allele was 4.1 (95% CI, 1.1 to 15.2), with
5.1% of the patients and 1.3% of the control subjects being carriers
of the prothrombin 20210A allele.2 This risk
was more pronounced than among men aged
The prothrombin 20210A allele was found to be a risk factor (OR,
2.8; 95% CI, 1.4 to 5.6) for deep-vein thrombosis in the LETS
study1 and two other recent
reports.7 8 This relative risk for venous
thrombosis was more pronounced than that in our case-control study of
myocardial infarction. A discrepancy in relative risks for venous and
arterial thrombosis has also been demonstrated for genetic
variations in other clotting factors. Factor V Leiden mutation (1691
G
When we consider the risk of myocardial infarction in the presence of a
coagulation defect (ie, carriership of the prothrombin 20210A
allele or factor V Leiden mutation), synergy is found. Smokers, the
obese, and persons with diabetes or hypertension (ie, persons with one
or more metabolic risk factor) have, in combination with a
coagulation defect, a higher risk of myocardial infarction compared
with noncarriers with the particular cardiovascular
risk factor. In each instance, the risk of the combination of the
coagulation defect with a risk factor exceeded the risk of the single
risk factor. This is in accordance with the results of the previous
study in young women, although the synergy was far more striking in
that study.2 It should be noted that the overall
risk of myocardial infarction is much lower in young women than in
middle-aged and elderly men (based on Dutch estimates (SIG Health Care
Information, National Medical Registration, tables on hospital
admissions, 1992 to 1994; available from Maliebaan 50, PO Box 14066,
3508 SC Utrecht, Netherlands), with an incidence of
1.5/10 000 person-years for women aged 35 to 39 years and 60/10 000
person-years for men aged 55 to 59 years). This implies that in terms
of public health or individual risk estimates, an 1.5-fold increased
risk in elderly men may be more important than a fourfold increase in
the risk among young women. For every group of 10 000 men aged 55 to
59 years, there is an increase in the number of individuals
experiencing a myocardial infarction of 30, whereas among every 10 000
women aged 35 to 39 years, the additional number of patients with a
myocardial infarction patients is 5. The high background risk in
elderly men also explains why even with the large study population and
powerful case-control design of the present study, effects are more
difficult to detect than among young women and often do not reach
statistical significance.
The frequency of the prothrombin 20210 AG genotype in control
subjects in the Study of Myocardial Infarctions Leiden was 1.2%, which
is similar to that of the control group of the case-control study among
young women2 and equal to the prevalence in 164
healthy plasma donors from the United Kingdom.7
In the LETS study, however, the percentage among healthy persons was
2.3%.1 We studied additional control groups in
the Netherlands to investigate this apparent discrepancy: in patients
with rheumatic arthritis, 5 of 291 (1.7%) were carriers of the
prothrombin 20210A allele, whereas in 249 blood donors, 8 carriers
(3.2%) were found (data not shown). These figures are in line with the
actual frequency of the prothrombin variant of 2%.12
The present study has two limitations. First, the results are
derived from men born in the Netherlands and do not necessarily apply
to other populations. The second is that of necessity we studied
patients who survived the myocardial infarction. It cannot be excluded
that patients who died during the acute phase of the myocardial
infarction more often carried the prothrombin 20210A allele or
factor V Leiden mutation. We think this is unlikely, however, because
survival of an individual after myocardial infarction is influenced by
other factors, such as patient-induced delay and delay in receipt of
effective assistance, which affect the time period from the onset of
symptoms to the start of interventions such as
thrombolytic therapy.12 Several
other factors influencing 30-day mortality rates are the level of
systolic blood pressure, heart rate, Killip class, and
localization of myocardial infarction.13 It does
not seem likely that the prothrombotic genotypes would play a
major role.
In conclusion, the results of the present study show that genetic
variations in thrombotic risk factors, such as prothrombin 20210A and
factor V Leiden mutation, increase the risk of myocardial infarction in
men. The risk is particularly increased when other
cardiovascular risk factors are present as well.
Given the high frequency of these genetic abnormalities in the general
population and the high prevalence of cardiovascular
risk factors, the need for prevention or treatment of these latter risk
factors is supported.
Received October 14, 1997;
accepted November 23, 1997.
2.
Rosendaal FR, Siscovick DS, Schwartz SM, Psaty BM,
Raghunathan TE, Vos HL. A common prothrombin variant (20210G to A)
increases the risk of myocardial infarction in young women.
Blood. 1997;90:1747–1750.
3.
Rosendaal FR, Siscovick DS, Schwartz SM, Beverly RK,
Psaty BM, Longstreth WT, Raghunathan TE, Koepsell TD, Reitsma PH.
Factor V Leiden (Resistance to activated protein C) increases
the risk of myocardial infarction in young women. Blood. 1997;89:2817–2821.
4.
Miller SA, Dykes DD, Polesky HF. A simple salting out
procedure for extracting DNA from human nucleated cells. Nucleic
Acids Res. 1988;16:1215.
5.
Bertina RM, Koeleman BPC, Koster T, Rosendaal FR,
Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood
coagulation factor V associated with resistance to activated
protein C. Nature. 1994;369:64–67.[Medline]
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6.
Woolf B. On estimating the relation between blood
group and disease. Ann Hum Genet. 1955;19:251–253.[Medline]
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7.
Cumming AM, Keeney S, Salden A, Bhavnani M, Shwe KH,
Hay CRM. The prothrombin gene G20210A variant: prevalence in a UK
anticoagulant clinic population. Br J Haematol. 1997;98:353–355.[Medline]
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8.
Hillarp A, Zöller B, Svensson PJ, Dahlbäck
B. The 20210A allele of the prothrombin gene is a common risk
factor among Swedish outpatients with verified deep venous thrombosis.
Thromb Haemost. 1997;78:990–992.[Medline]
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9.
Koster T, Rosendaal FR, de Ronde H, Briët E,
Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor
anticoagulant response to activated protein C: Leiden
Thrombophilia Study. Lancet. 1993;342:1503–1506.[Medline]
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10.
Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH.
High risk of thrombosis in patients homozygous for factor V Leiden
(activated protein C resistance). Blood. 1995;85:1504–1508.
11.
Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ,
Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation
factor V and the risk of myocardial infarction, stroke, and venous
thrombosis in apparently healthy men. N Engl J
Med. 1995;332:912–917.
12.
Rosendaal FR, Doggen CJM, Zivelin A, Arruda VR, Aiach
M, Siscovick DS, Hillarp A, Watzke HH, Bernardi F, Cumming AM, Preston
FE, Reitsma PH. Geographic distribution of the 20210 G to A prothrombin
variant. Thromb Haemost. In press.
13.
Leitch JW, Birbara T, Freedman B, Wilcox I, Harris PJ.
Factors influencing the time from onset of chest pain to arrival at
hospital. Med J Aust. 1989;150:6–10.[Medline]
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14.
Lee KL, Woodlief LH, Topol EJ, Weaver WD, Betriu A, Col
J, Simoons M, Aylward P, van de Werf F, Califf RM. Predictors of 30-day
mortality in the era of reperfusion for acute myocardial infarction:
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Circulation. 1995;91:1659–1668.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Interaction of Coagulation Defects and Cardiovascular Risk Factors
Increased Risk of Myocardial Infarction Associated With Factor V Leiden or Prothrombin 20210A
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
Background—A genetic variation
located in the 3'-untranslated region of the prothrombin gene
(prothrombin 20210 G
A) was recently described as a risk factor for
venous thrombosis. We examined how the presence of this mutation
affected the risk of myocardial infarction in a population-based
case-control study. Furthermore, we studied the risk of myocardial
infarction associated with the simultaneous presence of a
coagulation defect (ie, the 20210 AG genotype of prothrombin or
the factor V Leiden mutation) and major cardiovascular
risk factors. A variant of
prothrombin is associated with an increased risk of myocardial
infarction. The combined presence of major
cardiovascular risk factors and carriership of a
coagulation defect increases the risk considerably.
Key Words: myocardial infarction • coagulation • thrombosis • genetics • risk factors
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
Recently, a genetic
variation in the 3'-untranslated region of the prothrombin (clotting
factor II) gene was described that was associated with an elevated
prothrombin level.1 Individuals with a GA
transition at nucleotide 20210 (AG
genotype) had a mean prothrombin level of 1.32 U/mL, whereas
individuals with the GG genotype had a significantly
lower mean prothrombin level of 1.05 U/mL. Individuals with the
AG genotype had a 2.8-fold increased risk of venous
thrombosis compared with individuals with the 20210 GG
genotype in the Leiden Thrombophilia Study (LETS). In this
population-based case-control study, 6.2% of 474 unselected
consecutive patients with a first, objectively confirmed episode of
deep-vein thrombosis carried the prothrombin 20210A allele compared
with 2.3% of 474 control subjects matched for age and sex. In a
population of selected patients with a personal and family history of
venous thrombosis, 18% were carriers of this
allele.1 A) and myocardial infarction. In this case-control
study in women 18 to 44 years old, the presence of the AG
genotype increased the risk of myocardial infarction by
4.1-fold.2 In the same study, the 1691 GA
mutation in the gene of clotting factor V (factor V Leiden), which
causes resistance to activated protein C, was shown to be
related to the occurrence of arterial thrombosis at a young
age: the risk of myocardial infarction was 2.3-fold increased in
heterozygotes for the factor V Leiden mutation.3
The AG genotype of prothrombin gene and factor V
Leiden mutation both increased the risk of myocardial infarction,
particularly in the presence of other cardiovascular
risk factors, such as smoking or metabolic risk factors
(obesity, diabetes, hypertension,
hypercholesterolemia).2 A genetic variant
and myocardial infarction is unknown; we therefore studied the
association of the genetic variation in the 3'-untranslated region of
the prothrombin gene and the factor V Leiden mutation with myocardial
infarction in the population-based case-control Study of Myocardial
Infarctions Leiden, which includes 560 men with a first myocardial
infarction and 646 control subjects. Second, we examined the
interaction between these genetic variations and other known
cardiovascular risk factors with regard to the risk of
myocardial infarction.
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
Subjects
We conducted the population-based case-control Study of
Myocardial Infarctions Leiden between July 1994 and February
1997. 
6 months before participation in the study.
A morning fasting blood sample was drawn from the antecubital
vein into two Sarstedt Monovette tubes containing 0.106 mmol/L
trisodium citrate. We separated the blood sample into plasma and cells
through centrifugation. High-molecular-weight DNA was
extracted from the white blood cells according to a salting-out
method.4 The DNA was stored at 4°C until
amplification. Analyzable DNA was available for 560 patients and 646
control subjects. A) was determined by
the presence of a HindIII restriction site in the polymerase
chain reaction fragment according to the method of Poort et
al.1 Genetic analysis of the factor V
Leiden mutation (1691 GA) was performed with polymerase chain
reaction as described previously.5
An odds ratio (OR) was calculated as a measure of relative risk.
This OR estimates the risk of a myocardial infarction in the presence
of a risk factor relative to the absence of the particular risk factor,
the reference category. A 95% confidence interval (CI) was calculated
according to the method of Woolf.6 When the CI
did not include unity, the OR was different from unity at a
significance level of 
5%. Multiple logistic regression was performed
to adjust for age, with CIs for the adjusted ORs calculated with the
use of the standard errors of the coefficients estimated according to
the maximum likelihood methods. Mean values are presented with
standard deviation (SD). All computations were carried out with the
SPSS for Windows Version 7.0 statistical package.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
The characteristics of all patients and control subjects and
separately for those below the age of 50 years are shown in Table 1
. The mean age of the patients was 56.2
years (SD, 9.0 years), and that of control subjects was 57.3 years (SD,
10.8 years). A higher percentage of patients smoked and a lower
percentage used alcohol compared with the control subjects (62.3% and
33.3% smoked and 80.4% and 86.8% consumed alcohol, respectively).
The risk factors of obesity, diabetes, hypertension, and
hypercholesterolemia were more often found in
patients than in control subjects, with the most striking contrast in
younger persons.
View this table:
[in a new window]
Table 1. Characteristics of Patients1
and Control Subjects in
the Study of Myocardial Infarctions Leiden
In 10 of 560 patients (1.8%), the heterozygous (20210 AG)
genotype of prothrombin variant was detected compared with 8 of
646 control subjects (1.2%). Homozygous (20210 AA) carriers were not
found. The relative risk of myocardial infarction associated with
prothrombin 20210A carriership was 1.5 (95% CI, 0.6 to 3.8) (Table 2). In the subgroup of 314 men aged 50
years, no increased risk was found (OR, 0.9; 95% CI, 0.1 to 6.7). Only
4 persons in this young group were carriers of the prothrombin 20210A
allele: 2 patients and 2 control subjects.
View this table:
[in a new window]
Table 2. Frequency of the 20210 GA Genotypes in the
Prothrombin Gene, 1691 GA Genotypes in the Factor V Gene, and
Risk of Myocardial Infarction in 560 Patients and 646 Control Subjects 
). One patient
was a homozygous carrier of factor V Leiden mutation (age 63 at the
time of infarction). For the 314 men below the age of 50, the risk was
1.8 (95% CI, 0.8 to 3.9).
Overall, 48 patients (8.6%) and 39 control subjects (6.0%) had a
coagulation defect (ie, was a carrier of either prothrombin 20210A or
factor V Leiden mutation). One individual (age 64 years) who was member
of the control group was heterozygous for both mutations. The relative
risk of myocardial infarction in the presence of a coagulation defect
was 1.4 (95% CI, 0.9 to 2.2) overall and 1.6 (95% CI, 0.8 to 3.4) for
men below the age of 50.
Among smokers with the coagulation defect, the risk of a
myocardial infarction was increased sixfold compared with nonsmokers
without the abnormality. In comparison, smokers without the abnormality
had a relative risk of 
3 (Table 3). A
similar indication of a synergistic effect was found for other risk
factors (Tables 3 and 4). The single
effect of obesity, diabetes, hypertension, or
hypercholesterolemia (ie, the presence of one
or more metabolic risk factors) was small without the
concomitant presence of coagulation defect, whereas a substantial
increase in the risk of myocardial infarction was found when the
abnormality was present in combination with one of these risk
factors, ranging from a threefold to sixfold increase relative to those
with neither risk factor nor coagulation defect. No clear evidence for
synergy was found for persons using alcohol. The individuals who
account for the excess risks in the different strata are not the same
in each stratum in that only 21 of 87 persons with a coagulation defect
had two or more cardiovascular risk factors
simultaneously.
View this table:
[in a new window]
Table 3. Risk Effect of Smoking and a Metabolic
Risk Factor, Without and With a Coagulation Defect
View this table:
[in a new window]
Table 4. Risk Effect of Obesity, Diabetes Mellitus,
Hypertension, and Hypercholesterolemia, Without
and With a Coagulation Defect
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
The results of our population-based case-control Study of
Myocardial Infarctions Leiden show that the mutation in the prothrombin
gene (20210 GA) increases the risk of myocardial infarction by 50%
(OR, 1.5; 95% CI, 0.6 to 3.8). In patients, 1.8% were heterozygous
for the prothrombin 20210A allele compared with 1.2% of control
subjects. The risk of myocardial infarction was increased considerably
when a coagulation defect (ie, the prothrombin 20210A allele or
factor V Leiden mutation) was present simultaneously
with a cardiovascular risk factor, such as smoking. 50 years in the present
study, in whom we found no increased risk. It should be noted, however,
that only 4 young men carried the prothrombin 20210A allele and
that the CIs were wide. Factors such as hormonal status and the use of
oral contraception might interact in the association of the prothrombin
20210 GA genetic variant and myocardial infarction in women and
account for the varying results between the sexes. In addition, the
previous study included women living in western Washington, whereas our
study was conducted in men born in the Netherlands. A), for example, is the most common risk factor for venous
thrombosis. Heterozygous carriers of the mutation have a sevenfold
increased risk of venous thrombosis9 ; homozygous
individuals have a risk that is increased up to
80-fold.10 However, results of studies in which
the factor V Leiden mutation was examined as a potential risk factor
for myocardial infarction are
inconsistent,3 11 most likely because the
excess risk is less pronounced or present only in specific
groups.
Acknowledgments
This research was supported by the Netherlands Heart Foundation
(grant 92.345). The authors thank the cardiologists of the Departments
of Cardiology, Leiden University Hospital and Hospital
Diaconessenhuis Leiden, and F.J.M. van der Meer, head of the Leiden
Anticoagulant Clinic. We also thank P.E. Slagboom and C.L. Verweij for
providing blood samples from blood donors and patients with rheumatoid
arthritis. We particularly would like to thank the laboratory
technicians T. Visser and E. Vogels, who performed the DNA
analysis. For secretarial and administrative support, we are
indebted to J.J. Schreijer. We also express our gratitude to all
individuals who participated in the Study of Myocardial
Infarctions Leiden.
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
1.
Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A
common genetic variation in the 3'-untranslated region of the
prothrombin gene is associated with elevated plasma prothrombin levels
and an increase in venous thrombosis. Blood. 1996;88:3698–3703.
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 N. von Ahsen and M. Oellerich The intronic prothrombin 19911A>G polymorphism influences splicing efficiency and modulates effects of the 20210G>A polymorphism on mRNA amount and expression in a stable reporter gene assay system Blood, January 15, 2004; 103(2): 586 - 593. [Abstract] [Full Text] [PDF]
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P. M. Mannucci, D. Ardissino, P. A. Merlini, F. Peyvandi, Y.-G. Xie, C. Butt, and E. Randell Vagaries of genetic association studies in myocardial infarction Blood, August 15, 2003; 102(4): 1558 - 1560. [Full Text] [PDF]
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C. Butt, H. Zheng, E. Randell, D. Robb, P. Parfrey, and Y.-G. Xie Combined carrier status of prothrombin 20210A and factor XIII-A Leu34 alleles as a strong risk factor for myocardial infarction: evidence of a gene-gene interaction Blood, April 15, 2003; 101(8): 3037 - 3041. [Abstract] [Full Text] [PDF]
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I Y Tiong, M L Alkotob, and S Ghaffari Protein C deficiency manifesting as an acute myocardial infarction and ischaemic stroke Heart, February 1, 2003; 89(2): e7 - 7. [Abstract] [Full Text] [PDF]
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F. L Ruberg and J. Loscalzo Prothrombotic determinants of coronary atherothrombosis Vascular Medicine, November 1, 2002; 7(4): 289 - 299. [Abstract] [PDF]
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E. Sehnal and J. Slany Fibrinogen--the key to familial CHD or just another shadow in Plato's Allegory? Eur. Heart J., August 2, 2002; 23(16): 1231 - 1233. [PDF]
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K. Juul, A. Tybjarg-Hansen, R. Steffensen, S. Kofoed, G. Jensen, and B. G. Nordestgaard Factor V Leiden: The Copenhagen City Heart Study and 2 meta-analyses Blood, June 17, 2002; 100(1): 3 - 10. [Abstract] [Full Text] [PDF]
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F.R. Rosendaal, F.M. Helmerhorst, and J.P. Vandenbroucke Female Hormones and Thrombosis Arterioscler Thromb Vasc Biol, February 1, 2002; 22(2): 201 - 210. [Abstract] [Full Text] [PDF]
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F. Burzotta, K. Paciaroni, V. De Stefano, P. Chiusolo, A. Manzoli, I. Casorelli, A.M. Leone, E. Rossi, G. Leone, A. Maseri, et al. Increased prevalence of the G20210A prothrombin gene variant in acute coronary syndromes without metabolic or acquired risk factors or with limited extent of disease Eur. Heart J., January 1, 2002; 23(1): 26 - 30. [Abstract] [Full Text] [PDF]
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 S. M. Boekholdt, N. R. Bijsterveld, A. H.M. Moons, M. Levi, H. R. Buller, and R. J.G. Peters Genetic Variation in Coagulation and Fibrinolytic Proteins and Their Relation With Acute Myocardial Infarction: A Systematic Review Circulation, December 18, 2001; 104(25): 3063 - 3068. [Abstract] [Full Text] [PDF]
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A. Sramek, J.H.C. Reiber, W.B.J. Gerrits, and F.R. Rosendaal Decreased Coagulability Has No Clinically Relevant Effect on Atherogenesis: Observations in Individuals With a Hereditary Bleeding Tendency Circulation, August 14, 2001; 104(7): 762 - 767. [Abstract] [Full Text] [PDF]
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Y. Mira, J. Todoli, R. Alonso, M. L. Mico, A. Vaya, F. Ferrando, A. Estelles, P. Villa, and J. Aznar Factor V Leiden and Prothrombin G20210A in Relation to Arterial and/or Vein Rethrombosis: Two Cases Clinical and Applied Thrombosis/Hemostasis, July 1, 2001; 7(3): 234 - 237. [Abstract] [PDF]
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C. Russo, D. Girelli, O. Olivieri, P. Guarini, F. Manzato, F. Pizzolo, B. Zaia, A. Mazzucco, and R. Corrocher G20210A Prothrombin Gene Polymorphism and Prothrombin Activity in Subjects With or Without Angiographically Documented Coronary Artery Disease Circulation, May 22, 2001; 103(20): 2436 - 2440. [Abstract] [Full Text] [PDF]
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P. W. Kamphuisen, J. C. J. Eikenboom, and R. M. Bertina Elevated Factor VIII Levels and the Risk of Thrombosis Arterioscler Thromb Vasc Biol, May 1, 2001; 21(5): 731 - 738. [Full Text] [PDF]
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 T C F Sykes, C Fegan, and D Mosquera Thrombophilia, polymorphisms, and vascular disease Mol. Pathol., December 1, 2000; 53(6): 300 - 306. [Abstract] [Full Text]
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N. S. Van de Water, J. K. French, M. Lund, T. A. Hyde, H. D. White, and P. J. Browett Prevalence of factor v leiden and prothrombin variant g20210a in patients age <50 years with no significant stenoses at angiography three to four weeks after myocardial infarction J. Am. Coll. Cardiol., September 1, 2000; 36(3): 717 - 722. [Abstract] [Full Text] [PDF]
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A. Nguyen State-of-the-Art Review : Review and Management of Patients With the Prothrombin G20210A Polymorphism Clinical and Applied Thrombosis/Hemostasis, April 1, 2000; 6(2): 94 - 99. [Abstract] [PDF]
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A. Vaya, R. Trenor, S. Molla, A. Estelles, Y. Mira, P. Villa, and J. Aznar Acute Myocardial Infarction Associated With the Prothrombin G20210A Mutation Clinical and Applied Thrombosis/Hemostasis, April 1, 2000; 6(2): 111 - 112. [PDF]
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D. A. Lane and P. J. Grant Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease Blood, March 1, 2000; 95(5): 1517 - 1532. [Full Text] [PDF]
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G. Kunz, H. A. Ireland, P. J. Stubbs, M. Kahan, G. C. Coulton, and D. A. Lane Identification and characterization of a thrombomodulin gene mutation coding for an elongated protein with reduced expression in a kindred with myocardial infarction Blood, January 15, 2000; 95(2): 569 - 576. [Abstract] [Full Text] [PDF]
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S. Butenas, C. van't Veer, and K. G. Mann "Normal" Thrombin Generation Blood, October 1, 1999; 94(7): 2169 - 2178. [Abstract] [Full Text] [PDF]
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J. R. Meinardi, P. M. Pelsma, H. Koning, J. van der Meer, and K. Hamulyak Double-Homozygosity for Factor V Leiden and the Prothrombin Gene G20210A Variant in a Young Patient With Idiopathic Venous Thrombosis Blood, September 1, 1999; 94(5): 1828 - 1829. [Full Text] [PDF]
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A. J. Moss, R. E. Goldstein, V. J. Marder, C. E. Sparks, D. Oakes, H. Greenberg, H. J. Weiss, W. Zareba, M. W. Brown, C.-S. Liang, et al. Thrombogenic Factors and Recurrent Coronary Events Circulation, May 18, 1999; 99(19): 2517 - 2522. [Abstract] [Full Text] [PDF]
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M. Redondo, H. H. Watzke, B. Stucki, I. Sulzer, F. D. Biasiutti, B. R. Binder, M. Furlan, B. Lammle, and W. A. Wuillemin Coagulation Factors II, V, VII, and X, Prothrombin Gene 20210G->A Transition, and Factor V Leiden in Coronary Artery Disease : High Factor V Clotting Activity Is an Independent Risk Factor for Myocardial Infarction Arterioscler Thromb Vasc Biol, April 1, 1999; 19(4): 1020 - 1025. [Abstract] [Full Text] [PDF]
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A. Inbal, D. Freimark, B. Modan, A. Chetrit, S. Matetzky, N. Rosenberg, R. Dardik, Z. Baron, and U. Seligsohn Synergistic Effects of Prothrombotic Polymorphisms and Atherogenic Factors on the Risk of Myocardial Infarction in Young Males Blood, April 1, 1999; 93(7): 2186 - 2190. [Abstract] [Full Text] [PDF]
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P. M. Ridker, C. H. Hennekens, and J. P. Miletich G20210A Mutation in Prothrombin Gene and Risk of Myocardial Infarction, Stroke, and Venous Thrombosis in a Large Cohort of US Men Circulation, March 2, 1999; 99(8): 999 - 1004. [Abstract] [Full Text] [PDF]
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L. L. Amowitz, A. L. Komaroff, J. P. Miletich, P. M. Ridker;, F.R. Rosendaal, and D.S. Siscovick Factor V Leiden Is Not a Risk Factor for Myocardial Infarction Among Young Women Blood, February 15, 1999; 93(4): 1432 - 1433. [Full Text] [PDF]
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 P. C. Y. Liaw, T. Mather, N. Oganesyan, G. L. Ferrell, and C. T. Esmon Identification of the Protein C/Activated Protein C Binding Sites on the Endothelial Cell Protein C Receptor. IMPLICATIONS FOR A NOVEL MODE OF LIGAND RECOGNITION BY A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS 1-TYPE RECEPTOR J. Biol. Chem., March 9, 2001; 276(11): 8364 - 8370. [Abstract] [Full Text] [PDF]
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