Trial design: genetics
Prevalence of resistance against activated protein C resulting from factor V leiden is significantly increased in myocardial infarction: Investigation of 507 patients with myocardial infarction

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Abstract

Background

A point mutation in the gene encoding coagulation factor V is a cause of resistance against activated protein C. The presence of factor V Leiden is linked to 50% of congenital defects causing venous thrombosis. Its relationship to arterial thrombosis, particularly to myocardial infarction, has not been defined. Therefore, we performed a study on the role of factor V Leiden in patients with myocardial infarction. The study was carried out in Bavarians of German origin, a relatively homogeneous population.

Methods and results

The study group consisted of 507 patients with documented myocardial infarction (77.5% (393/507) men, 22.5% (114/507) women), with a mean age of 56.1 (range 18-–86) years. Strict criteria for patient selection and highly sensitive and specific functional tests for factor V Leiden were used. In addition, all patients with pathological test results were genotyped. The prevalence of factor V Leiden in patients with myocardial infarction was 8.7% (44/507), a significant increase in the prevalence of this mutation compared with the control group (3.7%, P = .0025). The odds ratio was 2.46 (95% CI 1.35–4.50).

Conclusions

A significantly increased prevalence of factor V Leiden in patients with documented myocardial infarction was seen. Patients with this mutation appear to have a predisposition for myocardial infarction.

Section snippets

Patients

The patient population comprised 507 patients who presented to a university hospital in Munich between September 1996 and March 2000. Inclusion criteria were documented prior myocardial infarction (increased creatine kinase [CK] with CK-MB >10% or proof of increased troponin I, typical alteration in the ECG, and typical clinical symptoms), with the first myocardial infarction date accurately recorded, together with written consent for the molecular genetic analysis (required in Bavaria since

Factor V leiden testing

The prevalence of the genetic defect leading to factor V Leiden in the Bavarian control group was 3.7% (15/404).

The modified functional test for factor V Leiden showed a mean activated protein C ratio of 2.3 (SEM ± 0.3) in all patients presenting with myocardial infarction. In patients with myocardial infarction and genotyping positive for heterozygous or homozygous factor V Leiden, the average activated protein C ratio was 1.5 (SEM ± 0.2). A pathological genotype was always associated with

Discussion

Coagulation disorders that increase thrombin generation associated with resistance against activated protein C and produce occlusive coronary episodes may represent additional risk factors for myocardial infarction. The risk may vary throughout the world. Regional differences in the prevalence of factor V Leiden have been documented in different geographical and ethnic populations worldwide, varying between 0.0% and 13.4%.36 Factor V Leiden is mostly limited to Caucasians and almost never found

Acknowledgements

We would like to thank Dorothea Nagel for help with the statistical analyses, and Peter Lohse for performing the genotyping of patients.

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