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Plasma proprotein‐convertase‐subtilisin/kexin type 9 (PCSK9) and cardiovascular events in type 2 diabetes
Author(s) -
El Khoury Petra,
Roussel Ronan,
Fumeron Frederic,
AbouKhalil Yara,
Velho Gilberto,
Mohammedi Kamel,
Jacob MariePaule,
Steg Philippe Gabriel,
Potier Louis,
Ghaleb Youmna,
Elbitar Sandy,
Ragot Stephanie,
Andreata Francesco,
Caligiuri Giusepinna,
Hadjadj Samy,
Boileau Catherine,
Marre Michel,
Abifadel Marianne,
Varret Mathilde,
Hansel Boris
Publication year - 2018
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13181
Subject(s) - pcsk9 , medicine , hazard ratio , stroke (engine) , myocardial infarction , type 2 diabetes , cardiology , kexin , incidence (geometry) , diabetes mellitus , heart failure , clinical endpoint , confidence interval , endocrinology , cholesterol , lipoprotein , clinical trial , ldl receptor , mechanical engineering , physics , optics , engineering
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.