B Cariou1, P Guérin2, C Le May3, V Letocart2, L Arnaud3, B Guyomarch4, M Pichelin5, V Probst6. 1. CHU de Nantes, l'Institut du Thorax, Department of Endocrinology, 44000 Nantes, France; CHU de Nantes, l'Institut du Thorax, Center of Clinical Investigation, 44000 Nantes, France; Inserm UMR 1087, CNRS UMR 6291, Université de Nantes, l'Institut du Thorax, 44000 Nantes, France. Electronic address: bertrand.cariou@univ-nantes.fr. 2. CHU de Nantes, l'Institut du Thorax, Department Cardiology, 44000 Nantes, France. 3. Inserm UMR 1087, CNRS UMR 6291, Université de Nantes, l'Institut du Thorax, 44000 Nantes, France. 4. CHU de Nantes, l'Institut du Thorax, Center of Clinical Investigation, 44000 Nantes, France; Inserm UMR 1087, CNRS UMR 6291, Université de Nantes, l'Institut du Thorax, 44000 Nantes, France. 5. CHU de Nantes, l'Institut du Thorax, Department of Endocrinology, 44000 Nantes, France; CHU de Nantes, l'Institut du Thorax, Center of Clinical Investigation, 44000 Nantes, France; Inserm UMR 1087, CNRS UMR 6291, Université de Nantes, l'Institut du Thorax, 44000 Nantes, France. 6. CHU de Nantes, l'Institut du Thorax, Center of Clinical Investigation, 44000 Nantes, France; CHU de Nantes, l'Institut du Thorax, Department Cardiology, 44000 Nantes, France.
Abstract
BACKGROUND: Serum proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations have been shown to be positively associated with LDL cholesterol (LDL-C), but the relationship between PCSK9 and coronary atherosclerosis lesions remains unclear. OBJECTIVE: This study aims to investigate the correlation between serum PCSK9 levels and coronary damage severity in patients hospitalized for acute coronary syndrome (ACS). METHODS: In this prospective proof-of-concept study, coronary lesions were assessed using SYNTAX scores. Serum PCSK9 concentrations were measured on admission (Day 0) for ACS by Elisa, and on every day of hospitalization. Spearman's correlations were used to determine the association between PCSK9 levels, SYNTAX score and metabolic parameters. RESULTS: A total of 174 patients (mean age: 59±14 years, 79% male) with ACS (on Day 0, 119 patients were not taking statins, but 55 were) were included. After initiation of high-intensity statin therapy, serum PCSK9 concentrations increased significantly, reaching maximum levels on Day 2 (+31% vs. Day 0), and remained stable up to Day 4 (P<0.001, by mixed model). Serum PCSK9 on Day 0 was associated with LDL-C (rho=0.226, P=0.017) and apolipoprotein B (rho=0.282, P=0.005) in the statin-naïve group only, and with triglycerides and non-HDL-C in all groups. More important, PCSK9 levels on Day 0 were positively associated with SYNTAX scores in the statin-naïve group (rho=0.239, P=0.009), but not in the statin-treated group (P=NS). This association was maintained after adjusting for LDL-C (P=0.014) and major CV risk factors (P=0.008). CONCLUSION: Serum PCSK9 levels are positively associated with severity of coronary artery lesions independently of LDL-C concentrations in patients hospitalized for ACS. This reinforces the potential importance of PCSK9 inhibition in the management of ACS.
BACKGROUND: Serum proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations have been shown to be positively associated with LDL cholesterol (LDL-C), but the relationship between PCSK9 and coronary atherosclerosis lesions remains unclear. OBJECTIVE: This study aims to investigate the correlation between serum PCSK9 levels and coronary damage severity in patients hospitalized for acute coronary syndrome (ACS). METHODS: In this prospective proof-of-concept study, coronary lesions were assessed using SYNTAX scores. Serum PCSK9 concentrations were measured on admission (Day 0) for ACS by Elisa, and on every day of hospitalization. Spearman's correlations were used to determine the association between PCSK9 levels, SYNTAX score and metabolic parameters. RESULTS: A total of 174 patients (mean age: 59±14 years, 79% male) with ACS (on Day 0, 119 patients were not taking statins, but 55 were) were included. After initiation of high-intensity statin therapy, serum PCSK9 concentrations increased significantly, reaching maximum levels on Day 2 (+31% vs. Day 0), and remained stable up to Day 4 (P<0.001, by mixed model). Serum PCSK9 on Day 0 was associated with LDL-C (rho=0.226, P=0.017) and apolipoprotein B (rho=0.282, P=0.005) in the statin-naïve group only, and with triglycerides and non-HDL-C in all groups. More important, PCSK9 levels on Day 0 were positively associated with SYNTAX scores in the statin-naïve group (rho=0.239, P=0.009), but not in the statin-treated group (P=NS). This association was maintained after adjusting for LDL-C (P=0.014) and major CV risk factors (P=0.008). CONCLUSION: Serum PCSK9 levels are positively associated with severity of coronary artery lesions independently of LDL-C concentrations in patients hospitalized for ACS. This reinforces the potential importance of PCSK9 inhibition in the management of ACS.
Authors: Thor Ueland; Ola Kleveland; Annika E Michelsen; Rune Wiseth; Jan Kristian Damås; Pål Aukrust; Lars Gullestad; Bente Halvorsen; Arne Yndestad Journal: Open Heart Date: 2018-09-18