Relationship of PCSK9 and Urinary Thromboxane Excretion to Cardiovascular Events in Patients With Atrial Fibrillation

Abstract Background Soluble proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular events (CVEs) in patients who are at high cardiovascular risk. No data on the effect of PCSK9 levels in patients with atrial fibrillation (AF) are available. Objectives This study investigated the association between PCSK9 and CVEs in AF as well as the relationship between PCSK9 and urinary 11-dehydro-thromboxane B 2 (11-dh-TxB 2 ), a marker of platelet activation. Methods We conducted a prospective, single-center cohort study, including 907 patients with AF treated with vitamin K antagonists (3,865 patient-years), to assess CVEs, including fatal and nonfatal myocardial infarction, ischemic stroke, and cardiovascular death. At admission, plasma PCSK9 and urinary 11-dh-TxB 2 (n = 852) were measured. The population was divided into tertiles of PCSK9 for the analysis. Results The mean age of patients was 73.5 ± 8.2 years, and 43.0% were women. At follow-up, 179 CVEs (4.6%/year) occurred: 43 (15.3%), 49 (15.5%), and 87 (28.0%) in the first, second, and third tertiles of PCSK9, respectively (log-rank test p = 0.009). Patients with CVEs had higher median PCSK9 compared with those without (1,500 pg/ml [IQR: 1,000 to 2,300 pg/ml] vs. 1,200 pg/ml [IQR: 827 to 1,807 pg/ml], respectively; p  2 were significantly correlated (Spearman's rho: 0.665; p  Conclusions Plasma PCSK9 levels are associated with an increased risk of CVEs in patients with AF. The direct correlation between PCSK9 and 11-dh-TxB 2 suggests PCSK9 as a mechanism potentially implicated in platelet activation.