Luca Liberale1, Fabrizio Montecucco1,2,3, Ilaria Casetta4, Silva Seraceni5, Alessandro Trentini6, Marina Padroni4, Franco Dallegri1,2, François Mach7, Enrico Fainardi8, Federico Carbone1. 1. First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy. 2. IRCCS AOU San Martino - IST, Genoa, Italy. 3. Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy. 4. Department of Biological, Psychiatric and Psychological Science, Azienda Ospedaliera-Universitaria, Ferrara, Italy. 5. Istitute for Maternal and Child Health 'IRCCS Burlo Garofolo', Trieste, Italy. 6. Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy. 7. Division of Cardiology, Department of Medical Specialties, Foundation for Medical Researches, University of Geneva, Geneva, Switzerland. 8. Neuroradiology Unit, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.
Abstract
BACKGROUND: Soluble mediators have been investigated to predict the prognosis of acute ischaemic stroke (AIS). Among them, proprotein convertase subtilisin/kexin type 9 (PCSK9) might have both clinical and pathophysiological relevance. MATERIALS AND METHODS: All available serum samples from a cohort of patients with first AIS (n = 72) were tested for PCSK9 and included in this substudy analysis. The primary endpoint investigated the predictive value of early PCSK9 level variations (ΔPCSK9) from AIS onset to day 7 or from day 1 to day 7, towards a 90-day outcome by modified Rankin Scale (mRS). The secondary endpoint explored the association between ΔPCSK9 and the risk of major adverse cardiovascular events (MACEs). RESULTS: Decreased serum PCSK9 levels at days 1 and 7 were associated with poor clinical outcomes at day 90. At the cut-off point identified by ROC curve analysis (-61·28 ng/mL), ΔPCSK9 day 7-day 1 predicted a poor mRS at day 90 after AIS. ΔPCSK9 day 7-day 1 ≤ -61·28 ng/mL was associated with an increased rate of MACEs. CONCLUSION: A decrease in PCSK9 levels was a predictor for poor outcome and increased MACEs after AIS. Additional studies targeting post-AIS PCSK9 levels and activity are required to clarify the prognostic and pathophysiological relevance of PCSK9 after AIS.
BACKGROUND: Soluble mediators have been investigated to predict the prognosis of acute ischaemic stroke (AIS). Among them, proprotein convertase subtilisin/kexin type 9 (PCSK9) might have both clinical and pathophysiological relevance. MATERIALS AND METHODS: All available serum samples from a cohort of patients with first AIS (n = 72) were tested for PCSK9 and included in this substudy analysis. The primary endpoint investigated the predictive value of early PCSK9 level variations (ΔPCSK9) from AIS onset to day 7 or from day 1 to day 7, towards a 90-day outcome by modified Rankin Scale (mRS). The secondary endpoint explored the association between ΔPCSK9 and the risk of major adverse cardiovascular events (MACEs). RESULTS: Decreased serum PCSK9 levels at days 1 and 7 were associated with poor clinical outcomes at day 90. At the cut-off point identified by ROC curve analysis (-61·28 ng/mL), ΔPCSK9 day 7-day 1 predicted a poor mRS at day 90 after AIS. ΔPCSK9 day 7-day 1 ≤ -61·28 ng/mL was associated with an increased rate of MACEs. CONCLUSION: A decrease in PCSK9 levels was a predictor for poor outcome and increased MACEs after AIS. Additional studies targeting post-AIS PCSK9 levels and activity are required to clarify the prognostic and pathophysiological relevance of PCSK9 after AIS.
Authors: Kellie A Mitchell; Justin Xavier Moore; Robert S Rosenson; Ryan Irvin; Faheem W Guirgis; Nathan Shapiro; Monika Safford; Henry E Wang Journal: PLoS One Date: 2019-02-06 Impact factor: 3.240