Ricerc@Sapienza

Background. Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a high risk of thromboembolic stroke. In addition to thrombo-embolism, AF patients are at high risk of experiencing cardiovascular complications, such as myocardial infarction (MI), with a rate ranging from 0.5 to 4%/year. Patients with atrial fibrillation (AF) display enhanced platelet activation but the underlying mechanism is still unclear. We investigated 1) the association between soluble PCSK9 and CVEs in patients with AF, 2) the relationship between soluble PCSK9 and 11-dehydro-thromboxane (Tx) B2 , a specific marker product of platelet activation.
Methods. We will Prospectively perform a single-center cohort study including AF patients treated with vitamin K antagonists that will be followed-up for about 12 months to assess CVEs, including fatal/non-fatal myocardial infarction and ischemic stroke and cardiovascular death. At admission, plasma PCSK9 and urinary excretion of 11-dehydro-TxB2 will be measured.
The sample size or the study will be calculated in accordance with previous studies from our group aimed at include a sufficient number of events in order to significantly identify the role of a specific variable analysed in tertiles in predicting the event. Thus, we planned a power of 90% and a type I error rate of 5%, comparing a survival probability in the first tertile of 88% and 75% in the third tertile. Consequently, 72 events in the first and last tertile combined were planned in order to guarantee the prescribed power.

Expected results. We hypothesize that Plasma PCSK9 levels are associated with an increased risk of CVEs in AF patients. A direct correlation between PCSK9 and TxB2 biosynthesis could support , if verified, the role of PCSK9 as a mechanism implicated in platelet activation.