The Edinburgh Artery Study: is lytic activity bad for the heart?

relate to vascular risk seemed counter-intuitive as they are considered indicators of either enhanced fibrinolytic potential (tPA) or enhanced fibrinolysis (Ddimer). There are a number of ways of interpreting the data to explain this relationship. First is the view that enhanced fibrinolysis actually represents a protective response to an increasingly procoagulant milieu as risk factor clustering progresses. Second, as fibrin is an important component of atheroma, enhanced fibrinolysis may lead to plaque instability and increased risk of myocardial infarction. Finally, as tPA clusters with features of insulin resistance, it may be either having a clinical effect because of this association or acting as a risk marker without involvement in disease processes. It is currently not possible to state which of these positions is tenable, although a possible explanation is that tPA is elevated early in response to insulin resistance and later becomes involved in the processes of plaque rupture. Whilst coagulation processes have a fairly long history of involvement in vascular disease, it is only relatively recently with the advent of innovative cell biology techniques that the role of cellular components of the blood has become clearer. It is established that the macrophage has a role in atheroma formation, but the role of neutrophils has been less clear. Neutrophil elastase is an enzyme released by activated neutrophils that is involved in the solubilization of elastin, an important component of the extracellular matrix. There is abundant evidence that activation of this system occurs in chronic pulmonary disease in which inflammation plays a role. More recently evidence has emerged that indicates that elastase activity may be related to endothelial cell damage. This opens the door for an involvement in vascular disease and to support this, in a rat heart model, inhibition of neutrophil elastase was associated with cardioprotection from repetitive ischaemia and myocardial infarction. In the current study elevated elastase activity was associated with progression to myocardial infarction which provides support to the view that leukocytes and neutrophil elastase are important in vascular disorders. Taken overall, the current findings of the Edinburgh Artery Study provide further information on risk factor involvement in the progression to myocardial infarction in subjects with pre-existing coronary artery disease. The Edinburgh Artery Study is interesting because it is studying the propensity of See page 1607 for the article to which this Editorial refers