Baris Gencer1, Fabrizio Montecucco2, David Nanchen3, Federico Carbone2, Roland Klingenberg4, Nicolas Vuilleumier5, Soheila Aghlmandi6, Dik Heg6, Lorenz Räber7, Reto Auer3, Peter Jüni8, Stephan Windecker7, Thomas F Lüscher4, Christian M Matter4, Nicolas Rodondi9, François Mach10. 1. Cardiology Division, Geneva University Hospitals, Rue Gabrielle-Perret Gentil 4, Geneva 14 1211, Switzerland baris.gencer@hcuge.ch. 2. Cardiology Division, Geneva University Hospitals, Rue Gabrielle-Perret Gentil 4, Geneva 14 1211, Switzerland First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine and IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, 6 viale Benedetto XV, 16132 Genoa, Italy. 3. Department of Ambulatory Care and Community Medicine, Lausanne University, Lausanne, Switzerland. 4. Department of Cardiology, University Heart Center, University of Zurich, Zurich, Switzerland. 5. Laboratory Medicine Division, Geneva University Hospitals, Geneva, Switzerland. 6. Institute of Social and Preventive Medicine, Clinical Trials Unit, Department of Clinical Research, University of Bern, Bern, Switzerland. 7. Department of Cardiology, University Hospital of Bern, Bern, Switzerland. 8. Institute of Primary Health Care, University of Bern, Bern, Switzerland Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St Michael's Hospital, University of Toronto, Toronto, ON M5S, Canada. 9. Department of General Internal Medicine, University Hospital of Bern, Bern, Switzerland. 10. Cardiology Division, Geneva University Hospitals, Rue Gabrielle-Perret Gentil 4, Geneva 14 1211, Switzerland.
Abstract
AIMS: Proprotein convertase subtilisin kexin 9 (PCSK9) is an emerging target for the treatment of hypercholesterolaemia, but the clinical utility of PCSK9 levels to guide treatment is unknown. We aimed to prospectively assess the prognostic value of plasma PCSK9 levels in patients with acute coronary syndromes (ACS). METHODS AND RESULTS: Plasma PCSK9 levels were measured in 2030 ACS patients undergoing coronary angiography in a Swiss prospective cohort. At 1 year, the association between PCSK9 tertiles and all-cause death was assessed adjusting for the Global Registry of Acute Coronary Events (GRACE) variables, as well as the achievement of LDL cholesterol targets of <1.8 mmol/L. Patients with higher PCSK9 levels at angiography were more likely to have clinical familial hypercholesterolaemia (rate ratio, RR 1.21, 95% confidence interval, CI 1.09-1.53), be treated with lipid-lowering therapy (RR 1.46, 95% CI 1.30-1.63), present with longer time interval of chest pain (RR 1.29, 95% CI 1.09-1.53) and higher C-reactive protein levels (RR 1.22, 95% CI 1.16-1.30). PCSK9 increased 12-24 h after ACS (374 ± 149 vs. 323 ± 134 ng/mL, P < 0.001). At 1 year follow-up, HRs for upper vs. lower PCSK9-level tertiles were 1.13 (95% CI 0.69-1.85) for all-cause death and remained similar after adjustment for the GRACE score. Patients with higher PCSK9 levels were less likely to reach the recommended LDL cholesterol targets (RR 0.81, 95% CI 0.66-0.99). CONCLUSION: In ACS patients, high initial PCSK9 plasma levels were associated with inflammation in the acute phase and hypercholesterolaemia, but did not predict mortality at 1 year. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Proprotein convertase subtilisin kexin 9 (PCSK9) is an emerging target for the treatment of hypercholesterolaemia, but the clinical utility of PCSK9 levels to guide treatment is unknown. We aimed to prospectively assess the prognostic value of plasma PCSK9 levels in patients with acute coronary syndromes (ACS). METHODS AND RESULTS: Plasma PCSK9 levels were measured in 2030 ACS patients undergoing coronary angiography in a Swiss prospective cohort. At 1 year, the association between PCSK9 tertiles and all-cause death was assessed adjusting for the Global Registry of Acute Coronary Events (GRACE) variables, as well as the achievement of LDL cholesterol targets of <1.8 mmol/L. Patients with higher PCSK9 levels at angiography were more likely to have clinical familial hypercholesterolaemia (rate ratio, RR 1.21, 95% confidence interval, CI 1.09-1.53), be treated with lipid-lowering therapy (RR 1.46, 95% CI 1.30-1.63), present with longer time interval of chest pain (RR 1.29, 95% CI 1.09-1.53) and higher C-reactive protein levels (RR 1.22, 95% CI 1.16-1.30). PCSK9 increased 12-24 h after ACS (374 ± 149 vs. 323 ± 134 ng/mL, P < 0.001). At 1 year follow-up, HRs for upper vs. lower PCSK9-level tertiles were 1.13 (95% CI 0.69-1.85) for all-cause death and remained similar after adjustment for the GRACE score. Patients with higher PCSK9 levels were less likely to reach the recommended LDL cholesterol targets (RR 0.81, 95% CI 0.66-0.99). CONCLUSION: In ACS patients, high initial PCSK9 plasma levels were associated with inflammation in the acute phase and hypercholesterolaemia, but did not predict mortality at 1 year. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: José Tuñón; Lina Badimón; Marie-Luce Bochaton-Piallat; Bertrand Cariou; Mat J Daemen; Jesus Egido; Paul C Evans; Imo E Hoefer; Daniel F J Ketelhuth; Esther Lutgens; Christian M Matter; Claudia Monaco; Sabine Steffens; Erik Stroes; Cécile Vindis; Christian Weber; Magnus Bäck Journal: Cardiovasc Res Date: 2019-01-01 Impact factor: 10.787