Clot lysis time and the risk of myocardial infarction and ischaemic stroke in young women; results from the RATIO case-control study

Abstract

Reduced overall fibrinolytic capacity increases the risk of myocardial infarction (MI), as demonstrated in studies with predominantly male participants. We determined the influence of altered fibrinolysis on the risk of MI and ischaemic stroke (IS) in young women. The RATIO (Risk of Arterial Thrombosis In relation to Oral contraceptives) study is a population-based case-control study including young women with MI (n=203), IS (N=175) and 638 matched healthy controls. Fibrinolytic potential was determined with a tissue factor/tissue plasminogen activator induced clot-lysis assay. Odds ratios (OR) adjusted for cardiovascular risk factors were obtained with logistic regression. Clot-lysis time (CLT) was divided into tertiles based on the control group (T1-T3), with T2 as reference. Hypofibrinolysis (prolonged CLT) was associated with an increase in risk of MI (T3 vs. T2, OR 2·8; 95%confidence interval [CI] 1·7-4·7). Hyperfibrinolysis (decreased CLT) had no clear effect (T1 vs. T2, OR 1·6; 95% CI 0·9-2·9). Hypofibrinolysis did not affect the risk of IS (T3 vs. T2, OR 1·5; 95% CI 0·7-3·0), whereas hyperfibrinolysis increased this risk (T1 vs. T2, OR 4·1; 95% CI 2·1-8·0). Oral contraceptive use and smoking further increased these risks. Hypofibrinolysis increases the risk for MI in young women, a finding similar to previous studies. Counter-intuitively, hyperfibrinolysis increased the risk of IS four-fold, which suggests that MI and IS have different aetiologies.