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04.08.2016 | Article

ANGPTL2 is associated with an increased risk of cardiovascular events and death in diabetic patients

verfasst von: Barnabas Gellen, Nathalie Thorin-Trescases, Philippe Sosner, Elise Gand, Pierre-Jean Saulnier, Stéphanie Ragot, Mathilde Fraty, Stéphanie Laugier, Grégory Ducrocq, David Montaigne, Pierre Llaty, Vincent Rigalleau, Philippe Zaoui, Jean-Michel Halimi, Ronan Roussel, Eric Thorin, Samy Hadjadj

Erschienen in: Diabetologia | Ausgabe 11/2016

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Abstract

Aims/hypothesis

A high serum angiopoietin-like 2 (ANGPTL2) concentration is an independent risk factor for developing diabetes and is associated with insulin resistance and atherosclerosis. In this work, we have examined the impact of serum ANGPTL2 on improving cardiovascular (CV) risk stratification in patients with type 2 diabetes.

Methods

A prospective, monocentric cohort of consecutive type 2 diabetes patients (the SURDIAGENE cohort; total of 1353 type 2 diabetes patients; 58% men, mean ± SD age 64 ± 11 years) was followed for a median of 6.0 years for death as primary endpoint and major adverse CV events (MACE; i.e. CV death, myocardial infarction or stroke) as a secondary endpoint. Patients with end-stage renal disease, defined as a requirement for dialysis or a history of kidney transplantation, were excluded. Patients were grouped into quartiles according to ANGPTL2 concentrations at inclusion: <11.2 (Q1), 11.2–14.7 (Q2), 14.8–19.5 (Q3) or >19.5 (Q4) ng/ml.

Results

During follow up, 367 patients (representing 4.5% of the total person-years) died and 290 patients (representing 3.7% of the total person-years) presented with MACE. Both the survival and MACE-free survival rates were significantly different between ANGPTL2 quartiles (logrank 82.12, p < 0.0001 for death; and logrank 65.14, p < 0.0001 for MACE). Patients with ANGPTL2 concentrations higher than 19.5 ng/ml (Q4) had a significantly higher risk of death and MACE than those with ANGPTL2 levels of 19.5 ng/ml or less (Q1–3) (HR for death 2.44 [95% CI 1.98, 3.00], p < 0.0001; HR for MACE 2.43 [95% CI 1.92, 3.06], p < 0.0001) after adjustment for sex, age and established CV risk factors. Using ANGPTL2 concentrations, prediction of the risk of mortality, as assessed by integrated discrimination improvement (IDI), was significantly improved (IDI 0.006 ± 0.002, p = 0.0002).

Conclusions/interpretation

In patients with type 2 diabetes, serum ANGPTL2 concentrations were independently associated with death and MACE. Therefore, ANGPTL2 is a promising candidate biomarker for improving risk stratification in type 2 diabetes patients, and may prove to be a valuable therapeutic target.

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Titel: ANGPTL2 is associated with an increased risk of cardiovascular events and death in diabetic patients
verfasst von: Barnabas Gellen
Nathalie Thorin-Trescases
Philippe Sosner
Elise Gand
Pierre-Jean Saulnier
Stéphanie Ragot
Mathilde Fraty
Stéphanie Laugier
Grégory Ducrocq
David Montaigne
Pierre Llaty
Vincent Rigalleau
Philippe Zaoui
Jean-Michel Halimi
Ronan Roussel
Eric Thorin
Samy Hadjadj
Publikationsdatum: 04.08.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 11/2016
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-016-4066-5

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