Inherited thrombophilia and the risk of myocardial infarction: current evidence and uncertainties

Atherothrombotic diseases (ATEs) and venous thromboembolism (VTE) have been traditionally considered to have a distinct pathogenesis. Today, a growing body of evidence on the pathophysiology of thrombus formation has convincingly proved that they share more mutual risk factors than previously recognized. It has been shown in a number of case‑control studies that there is a significant risk for a subsequent cardiovascular disease after VTE, although this risk is low or at most moderate. In the past 2 decades, the role of each inherited risk factor for VTE in relation to ATE has been intensively studied. Unfortunately, a large body of contradictory findings has been published that hinders consensus and transformation of knowledge into clinical practice. Complicated gene‑gene interactions, small sample sizes, heterogeneous genetic and environmental patient backgrounds, confounding factors, and varied methodological designs may have contributed to opposing findings. In the case of rare thrombophilias, conclusions must be summarized based on case reports or case series, as only few case‑control and cohort studies are available. In this review we focus on available evidence and controversies regarding the relationship between the classic inherited VTE risk factors (factor V Leiden, prothrombin 20210A, deficiencies of antithrombin, protein C, and protein S) and the risk of myocardial infarction (MI). We conclude that the risk of MI in patients with common inherited thrombophilia is generally modest. However, in patients with deficiencies of antithrombin, protein C, or protein S, the risk of MI or other ATEs is not negligible. A personalized clinical approach is suggested when testing for inherited thrombophilia in a patient with MI.