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26/06/2012

VHIR’s study determines multiple applications for a novel stroke biomarker

Biomarcado ictus

26/06/2012

Phospholipase is a marker with enormous potential: risk of stroke, risk of recurrence, response to treatment and prognosis. Until now, there has been no such complete biomarker.

The Neurovascular Diseases Research Group of Vall d'Hebron Research Institute (VHIR) has worked on the study, detection and confirmation of a biomarker useful to predict recurrence in patients who have had a stroke or transient ischemic attack (TIA) and to predict the response to stroke treatment with fibrinolysis. The work of this group concludes and confirms the usefulness of phospholipase A (2) (Lp-PLA (2)) as a new biomarker of these cerebrovascular diseases. It has been seen that there have been important changes in Lp-PLA2 concentrations after a stroke, and this phospholipase predicts the possibility of having another one. This biomarker also predicts the response to intravenous fibrinolytic treatment determined by the recanalization of the cloned artery.

This biomarker, studied in detail by this group, provides a great deal of information about the pathological process that the patient is undergoing. On the one hand, we have begun to study the concentrations and activity of Lp-PLA (2) in patients who have had a first TIA (transient ischemic attack). In this situation, patients present symptomatology derived from the very short-lived and self-reversing stroke, although in no case can it be considered a less serious situation, given that the risk of early recurrence is very high. The levels of Lp-PLA (2) in these cases are already high. "These high levels of the marker have been related to certain risk factors and the study determines, for example, the relationship between high levels of Lp-PLA (2) and the presence of intracranial atherosclerotic plaques, often unstable and that can cause a stroke", explains Dr. Joan Montaner, head of this study group at VHIR.

In addition to all the results studied, the most recent publication in Cerebrovascular Disease determines the value of Lp-PLA activity (2) to add important prognostic information in the initial evaluation of patients with TIA, because its concentration and activity predict the increased risk of recurrence after TIA. A TIA with low phospholipase A2 activity will not have the same prognosis as a TIA with high Lp-PLA (2) and high activity. In the latter case, the risk of recurrence is much higher and, therefore, the study of the cause and preventive measures must be intensified to avoid a second episode of TIA or stroke.

But the study, conducted by VHIR and resulting in multiple publications in the journal Atherosclerosis, all of them recent, goes further and confirms, moreover, that Lp-PLA activity (2) is a clear indicator of the risk of having a stroke again when one has already had one, either a stroke itself or a TIA. "In fact, the findings we have made in our studies in relation to Lp-PLA (2) are very consistent and considerably expand on what has been known so far," explains Dr. Pilar Delgado, the first signatory of this series of publications. In those cases in which arterial reperfusion treatment aimed at restoring cerebral blood flow can be administered, Lp-PLA (2) predicts early response to fibrinolytic treatment with t-PA and therefore the possibility of recanalization of the artery. This is extremely important, according to Dr. Delgado. Delgado, because fibrinolysis is a treatment with important side effects, "If we balance the risk of the treatment or the severity of the pathology, it is obvious that we must try to recanalize the artery, but if we have a marker that indicates that the treatment will not work, we must think of other strategies," continues Dr. Delgado.

Stroke patients receiving t-PA (fibrinolytic) treatment have their intracranial arteries monitored by Doppler ultrasound to determine when the artery recanalization occurs. Blood samples are taken the first hour after treatment and the concentration and activity of this phospholipase is determined. Normally, its activity, at the acute moment of stroke (<4.5h) and after, recovers to normal. When the concentration of this enzyme is high during these first hours, there is little chance of rechanneling with t-PA and intra-arterial treatment must be considered, which is why it is useful as a marker of response to treatment, as it contributes to clinical decision-making.

"The great conclusion of this series of studies is the enormous potential of this marker, especially in determining risk, as it has proven to be very useful and has provided a great deal of information about what has happened to the patient. Until now, there was no biomarker so complete," concluded Dr. Montaner and continued, "in addition to providing a large amount of information, it does so quickly and relatively inexpensively because it is an analytical test. In places with few resources or far from centers where highly complex treatments can be performed, it can be very useful for differential diagnosis and to help determine the cause, predict the risk of recurrence, the need for preventive treatment of a second episode of stroke and the possibility of a better or better response to complex treatment".

Stroke kills 5.7 million people each year around the world, according to data from the World Health Organization (WHO). In Spain, it is the leading cause of death in women and is also the leading cause of death in Catalonia, where more than 13,000 people are admitted to hospital each year. Of these, more than 10% end in death during hospitalization and 30% result in permanent disability. Although stroke mainly affects older people, 18% of all cases are suffered by people under the age of 65.

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