Petra El Khoury1,2, Ronan Roussel3,4,5, Frederic Fumeron4,5, Yara Abou-Khalil1,2, Gilberto Velho5, Kamel Mohammedi3,5, Marie-Paule Jacob1,4, Philippe Gabriel Steg1,4,6,7, Louis Potier3,4,5, Youmna Ghaleb1,2,4, Sandy Elbitar1,2,4, Stephanie Ragot8,9,10, Francesco Andreata1,4, Giusepinna Caligiuri1,4, Samy Hadjadj8,9,10,11,12, Catherine Boileau1,4,13, Michel Marre3,4,5, Marianne Abifadel1,2, Mathilde Varret1,4, Boris Hansel3,4,5. 1. INSERM LVTS U1148, Hôpital Bichat-Claude Bernard, Paris, France. 2. Laboratory of Biochemistry and Molecular Therapeutics, Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Pôle Technologie- Santé, Saint-Joseph University, Beirut, Lebanon. 3. Département d'Endocrinologie, Diabétologie et Nutrition, DHU-FIRE, HUPNVS, AP-HP, CHU Xavier Bichat, Paris, France. 4. Université Paris Diderot-Sorbonne Paris Cité, Paris, France. 5. Centre de Recherche des Cordeliers, INSERM, U-1138, Paris, France. 6. FACT, HUPNVS, Département de Cardiologie, AP-HP, CHU Xavier Bichat, Paris, France. 7. NHLI, Imperial College, Royal Brompton Hospital, London, UK. 8. Centre Investigation Clinique 1402, University of Poitiers, Poitiers, France. 9. Centre Investigation Clinique, CHU Poitiers, Poitiers, France. 10. Centre Investigation Clinique CIC1402, INSERM, Poitiers, France. 11. Pole DUNE, CHU Poitiers, Poitiers, France. 12. U1082, INSERM, Poitiers, France. 13. Département de génétique, AP-HP, CHU Xavier Bichat, Paris, France.
Abstract
AIM: To investigate whether plasma concentrations of proprotein-convertase-subtilisin/kexin type 9 (PCSK9) were associated with cardiovascular (CV) events in two cohorts of patients with type 2 diabetes mellitus. METHODS: We considered patients from the DIABHYCAR (n = 3137) and the SURDIAGENE (n = 1468) studies. Baseline plasma PCSK9 concentration was measured using an immunofluorescence assay. In post hoc, but preplanned, analyses we assessed the relationship between PCSK9 and the following endpoints: (1) a combined endpoint of major CV events: CV death, non-fatal myocardial infarction (MI), stroke and heart failure-related hospital admission; (2) a composite of all CV events: MI, stroke, heart failure-related hospital admission, coronary/peripheral angioplasty or bypass, CV death; (3) MI; (4) stroke/transient ischaemic attack (TIA); and (5) CV death. RESULTS: In the DIABHYCAR study, plasma PCSK9 tertiles were associated with the incidence of MI, all CV events and stroke/TIA (P for trend <.05). In adjusted Cox analysis, plasma PCSK9 was associated, independently of classic risk factors, with the incidence of major CV events (hazard ratio [HR] for 1-unit increase of log[PCSK9] 1.28 [95% confidence interval {CI} 1.06-1.55]), the incidence of MI (HR 1.66 [95% CI 1.05-2.63]), and the incidence of all CV events (HR 1.22 [95% CI 1.04-1.44]), but not with CV death. Plasma PCSK9 was not associated with the incidence of CV disease in the participants of the SURDIAGENE study with high CV risk treated with statins and insulin. CONCLUSIONS: We found that PCSK9 was inconsistently associated with CV events in populations with type 2 diabetes. The association may depend on the level of CV risk and the background treatment.
AIM: To investigate whether plasma concentrations of proprotein-convertase-subtilisin/kexin type 9 (PCSK9) were associated with cardiovascular (CV) events in two cohorts of patients with type 2 diabetes mellitus. METHODS: We considered patients from the DIABHYCAR (n = 3137) and the SURDIAGENE (n = 1468) studies. Baseline plasma PCSK9 concentration was measured using an immunofluorescence assay. In post hoc, but preplanned, analyses we assessed the relationship between PCSK9 and the following endpoints: (1) a combined endpoint of major CV events: CV death, non-fatal myocardial infarction (MI), stroke and heart failure-related hospital admission; (2) a composite of all CV events: MI, stroke, heart failure-related hospital admission, coronary/peripheral angioplasty or bypass, CV death; (3) MI; (4) stroke/transient ischaemic attack (TIA); and (5) CV death. RESULTS: In the DIABHYCAR study, plasma PCSK9 tertiles were associated with the incidence of MI, all CV events and stroke/TIA (P for trend <.05). In adjusted Cox analysis, plasma PCSK9 was associated, independently of classic risk factors, with the incidence of major CV events (hazard ratio [HR] for 1-unit increase of log[PCSK9] 1.28 [95% confidence interval {CI} 1.06-1.55]), the incidence of MI (HR 1.66 [95% CI 1.05-2.63]), and the incidence of all CV events (HR 1.22 [95% CI 1.04-1.44]), but not with CV death. Plasma PCSK9 was not associated with the incidence of CV disease in the participants of the SURDIAGENE study with high CV risk treated with statins and insulin. CONCLUSIONS: We found that PCSK9 was inconsistently associated with CV events in populations with type 2 diabetes. The association may depend on the level of CV risk and the background treatment.
Authors: Aleksandr B Shek; Rano B Alieva; Ravshanbek D Kurbanov; Shavkat U Hoshimov; Ulugbek I Nizamov; Adolat V Ziyaeva Journal: Arch Med Sci Atheroscler Dis Date: 2019-07-18