Paper selected as most important paper

The editors of Circulation: Cardiovascular Interventions perform perform a periodic  ‘Topic Review’  which (and I quote)

summarizes the most important manuscripts, as selected by the editors that have published in the Circulation portfolio. The studies included in this article represent the most noteworthy research in the area of peripheral arterial disease. (Circ Cardiovasc Interv. 2012;5:e39-e44.)

Our research on the effect of activation of the intrinsic coagulation proteins and their effects on ischaemic stroke risk -and not on myocardial infarction risk- was selected as one of the most important manuscripts int he field of peripheral arterial disease. This study was performed in collaboration with the Maastricht University Medical Center. The summary by these editors can be read below.

Summary: Arterial forms of thrombosis are leading causes of deathand disability in the Western world. The Risk of Arterial Thrombosisin Relation to Oral Contraceptives (RATIO) study is a populationbasedcase control study that focuses on arterial thrombosis in youngwomen (18–50 years of age), and has a unique opportunity toidentify risk factors that are difficult to identify in older patientsbecause they could be obscured by age-related comorbidities. Theidentification of these new risk factors could aid in the preventionand treatment of arterial thrombosis in all age groups. This studyinvestigated whether proteins of the intrinsic coagulation pathwaysare risk factors for arterial thrombosis. Historically, the role of someof these factors was thought to be minor. However, both animal andclinical studies have implicated these proteins in pathophysiologicalthrombus formation. Furthermore, these proteins also play a role inother relevant biological systems, such as inflammation. Inhibitorcomplexes of coagulation factors XIIa, Xia, and kallikrein weredetermined as a measure of protein activation. It was found that thesecomplexes were higher in ischemic stroke cases, but were not higherin myocardial infarction cases when compared with matched controls.The risk of stroke was further increased (up to 23-fold) among  users of oral contraceptives. However, because of the low incidence of arterial thrombosis in young women, screening for these factors before the start of arterial thrombosis does not seem to be warranted. Further studies should be performed to investigate the exact pathophysiological mechanism and whether these mechanisms are different for the subtypes of arterial thrombosis, especially for subtypes of ischemic stroke. Conclusions: High levels of activated proteins of the intrinsic

coagulation system are associated with arterial thrombosis, whereas the strength of these associations differs for myocardial infarction and ischemic stroke. This contradicts similar analyses among men in the Northwick Park Heart Study. Together with the finding that oral contraceptive use further increases the risks, the question of whether the role of intrinsic coagulation proteins in the pathogenesis of arterial thrombosis is sex-specific is raised.

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