Increased tissue factor pathway inhibitor activity is associated with myocardial infarction in young women: results from the RATIO study

• Published in: Journal of thrombosis and haemostasis 2011-11, Vol.9 (11), p.2243-2250
• Main Authors: WINCKERS, K., SIEGERINK, B., DUCKERS, C., MAURISSEN, L. F., TANS, G., CASTOLDI, E., SPRONK, H. M. H., TEN CATE, H., ALGRA, A., HACKENG, T. M., ROSENDAAL, F. R.
• Format: Article
• Language: English
• Subjects: Adult; Anticoagulants; APC resistance; Cardiotonic Agents; Case-Control Studies; epidemiology; Female; Humans; Lipoproteins - blood; Lipoproteins - metabolism; Middle Aged; myocardial infarction; Myocardial Infarction - blood; Odds Ratio; protein S; Protein S - analysis; TFPI; Up-Regulation; Young Adult; young women
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/j.1538-7836.2011.04497.x

Background: The tissue factor pathway inhibitor (TFPI)/protein S anticoagulant system is a potent inhibitor of blood coagulation. TFPI and protein S are major determinants of thrombin generation (TG) tests determined at low tissue factor (TF) and at high TF concentrations in the presence of activated protein C (APC). Both TFPI and protein S protect against venous thrombosis, but the importance of the TFPI/protein S system in arterial thrombosis remains unclear. Objectives: To investigate the influence of the TFPI/protein S anticoagulant system on the risk of myocardial infarction (MI) in young women. Methods: The RATIO study is a case–control study in women under 50 years of age, including 205 patients and 638 controls. TFPI and protein S were quantified using ELISA. The TFPI/protein S activity (nTFPIr) and the APC sensitivity ratio (nAPCsr) were determined using TG tests. Odds ratios (ORs) adjusted for putative confounders and corresponding 95% confidence intervals (95% CI) were determined. Results: Women with MI had higher TFPI levels than controls (135.9 ± 40% vs. 124.2 ± 41%), resulting in increased TFPI/protein S activities and increased APC sensitivity. Furthermore, an increased TFPI activity was associated with MI [nTFPIr: adjusted OR Q1 vs. Q4 = 2.1 (95%CI 1.1–4.1)]. Additionally, an increased APC sensitivity was associated with MI [nAPCsr: adjusted OR Q1 vs. Q4 = 1.7 (95% CI 0.9–3.2)] Conclusion: Women with MI had increased TFPI levels compared with controls. Consequently, the TFPI/protein S activity and APC sensitivity are increased in women with MI. Whether this increase in TFPI activity acts as a compensating mechanism for an increased procoagulant state or is a marker of endothelial damage remains to be investigated.