Blood, Vol. 93 No. 4 (February 15), 1999:
pp. 1432-1433
CORRESPONDENCE
Factor V Leiden Is Not a Risk Factor for Myocardial Infarction
Among Young Women
 |
LETTER |
To the Editor:
Several large-scale studies indicate that factor V Leiden
(FVL) is not associated with an increased risk of acute myocardial infarction (MI) in middle-aged or elderly populations.1-7
However, Rosendaal et al8 have hypothesized that FVL might
increase the risk of myocardial infarction among women less than 45 years of age, particularly in the subgroup of smokers. Specifically, in
a study of 84 women with premature myocardial infarction, 8 were found
to carry FVL (binomial 95% confidence interval [CI], 4.2% to
17.9%). In the subgroup of smokers who carried FVL, 7 of 62 were found
to be carriers of FVL (binomial 95% CI, 4.6% to 21.9%). Based on
these data and on an observed control prevalence of 4.1%, the
investigators reported a 32-fold increased risk of MI among the
subgroup of young female smokers who carried FVL as compared with
nonsmokers free of the mutation.
To directly evaluate this hypothesis, we used polymerase chain
reaction techniques to determine FVL status among 36 women in the
Boston area who suffered a myocardial infarction before 45 years of age
and compared the prevalence of this mutation with an age-, ethnicity-,
and smoking-matched group of community-based controls, as well as with
the mutation rate previously reported in a large-scale population-based
study of FVL in the United States.9
The average age of case subjects at the time of the MI was 39 years; 52% were smokers. As expected, case subjects were heavier, more
likely to have a family history of premature atherothrombosis, and more
likely to be treated for hypertension and hyperlipidemia, as compared
with community-based controls.
We found no evidence in these data that FVL increased the risk
of MI (Table 1). Specifically, of the 36 case subjects, 1 (2.7%) was heterozygous for FVL, as compared with 3 (8.3%) of the controls (P = .3). Similarly, the prevalence
of the mutation in the case group (2.7%) was not statistically
different from the 4.8% prevalence rate previously reported in a
large-scale population-based study of American women free of any
history of coronary disease (P = .6). Moreover, in the
subgroup of smokers, only 1 of 19 (5.2%) case subjects with MI was
found to carry FVL.
Thus, these data do not support the hypothesis that FVL is an
important risk factor for MI among young women, regardless of smoking status.
| |
ACKNOWLEDGMENT |
L.L.A. is the recipient of a Clinical and Community Health Fellowship
from Fleet Investment Management, Trustee of Charles A. King Trust.
Lynn L. Amowitz
Anthony L. Komaroff
Joseph P. Miletich
Paul M. Ridker
Department of Medicine
Brigham and Women's
Hospital
Harvard Medical School
Boston, MA
| |
REFERENCES |
1.
Ridker PM, Hennekens CH, Lindpainter K, Stampfer MJ, Eisenberg PR, Miletich JP:
Mutation in gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men.
N Engl J Med
332:912, 1995[Abstract/Free Full Text]
2.
Van Bockxmeer FM, Baker RI, Taylor RR:
Premature ischaemic heart disease and the gene for coagulation factor V.
Nat Med
1:185, 1995[Medline]
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3.
Ardissimo D, Peyvandi F, Merlini PA, Colombi E, Mannucci PM:
Factor V (Arg506 
Gln) mutation in young survivors of myocardial infarction.
Thromb Haemost
75:701, 1996[Medline]
[Order article via Infotrieve]
4.
Emmerich J, Poirier O, Evans A, Marques-Vidal P, Arveiler D, Luc G, Aiach M, Cambien F:
Myocardial infarction, Arg506 to Gln factor V mutation, and activated protein C resistance.
Lancet
345:321, 1995[Medline]
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5.
März W, Seydewitz H, Winkelmann B, Chen M, Nanuck M, Witt I:
Mutation in coagulation factor V associated with resistance to activated protein C in patients with coronary artery disease.
Lancet
345:526, 1995[Medline]
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6.
Kontula K, Ylikorkala A, Miettinen H, Vuoris A, Kauppinen-Mäkelin R, Hämäliänen L, Palomäki H, Kaste M:
Arg506Gln factor V mutation (factor V Leiden) in patients with ischaemic cerebrovascular disease and survivors of myocardial infarction.
Thromb Haemost
73:558, 1995[Medline]
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7.
Cushman M, Rosendaal FR, Psaty BM, Cook EF, Valliere J, Kuller LH, Tracy RP:
Factor V Leiden is not a risk factor for arterial vascular disease in the elderly: Results from the Cardiovascular Health Study.
Thromb Haemost
79:912, 1998[Medline]
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8.
Rosendaal FR, Siscovick DS, Schwartz RK, Beverly BM, Psaty WT, 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
89:2817, 1997[Abstract/Free Full Text]
9.
Ridker PM, Miletich JP, Hennekens CH, Buring JE:
Ethnic distribution of factor V Leiden in 4047 men and women: Implications for venous thromboembolism for venous thromboembolism screening.
JAMA
277:1305, 1997[Abstract]
Response
To the Editor:
Myocardial infarction is a rare but devastating disease among young
women. There are few studies available, and data on genetic risk
factors are especially scarce. Therefore, the attempt of Amowitz et al
to evaluate our findings in a new study is commendable. However, the size of their study (36 patients) makes it difficult to
interpret their findings. This becomes clear when we look at the
confidence intervals of their results and our results.
We studied 84 patients and 388 controls and found (with prevalences of
carriership of factor V Leiden of 10% and 4%) a relative risk of 2.4, with a 95% confidence interval of 1.0 to 5.9.1 The risk
was 25- to 32-fold increased in carriers with other major risk factors,
as compared with noncarriers without other major risk factors. Amowitz
et al report 1 carrier among 36 patients (2.7%) and 3 among 36 controls (8.3), which leads to a relative risk of 0.3, with a
confidence interval of 0.01 to 4.20. From this we conclude that these
data neither support nor refute our previous, larger study. The large
discrepancy in the estimates of the carrier prevalence among controls
(8.3% among 36 controls and 4.8% among 948 controls) illustrates the
instability of estimates based on such small samples.
Recently, we have shown that another common prothrombotic mutation, the
20210 G to A variant of the protrombin gene, which is present in 2% to
4% of whites,2 increases the risk of myocardial infarction
fourfold in young women3 and that the combination of the
mutation with a major cardiovascular risk factor leads to a 43fold
increased risk (compared with women with neither). A further analogy
may be found in a large study among (mainly middleaged) men with
myocardial infarction (560 patients and 646 controls), to which we
found mildly elevated risks associated with both factor V
Leiden and prothrombin 20210A and also more pronounced risks in the
presence of other risk factors.4 We feel that the magnitude
of these risks estimates and the analogies between the two
abnormalities and the sexes indicate the associations to be real.
Nevertheless, we too are interested in extending these findings, for
which larger population-based studies are under way in Seattle and
Leiden.
F.R. Rosendaal
Hemostasis and
Thrombosis Research Center
Leiden University Medical
Center
Leiden, The Netherlands
D.S. Siscovick
Cardiovascular Health Research
Unit
University of Washington
Seattle, WA
| |
REFERENCES |
1.
Rosendaal FR, Siscovick DS, Schwartz SM, Beverly RK, Psaty BM, Longstreth WT Jr, Raghunathan TE, Koepsell TD, Reitsma PH:
Factor V Leiden (resistance to activated protein C) increases the risk of myocardial infarction in young women.
Blood
89:2817, 1997
2.
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
79:706, 1998[Medline]
[Order article via Infotrieve]
3.
Rosendaal FR, Siscovick DS, Schwartz SM, Psaty BM, Raghunathan TE, Vos HL:
A common prothrombin variant (20210 G to A) increases the risk of myocardial infarction in young women.
Blood
90:1747, 1997[Abstract/Free Full Text]
4.
Doggen CJM, Manger Cats V, Bertina RM, Rosendaal FR:
Interaction of coagulation defects and cardiovascular risk factors: Increased risk of myocardial infarction associated with factor V Leiden or prothrombin 20210A.
Circulation
97:1037, 1998[Abstract/Free Full Text]
