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.1-7However, 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.
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 5.9.1-1 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,1-2 increases the risk of myocardial infarction fourfold in young women1-3 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.1-4 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.
REFERENCES
ACKNOWLEDGMENT
L.L.A. is the recipient of a Clinical and Community Health Fellowship from Fleet Investment Management, Trustee of Charles A. King Trust.
