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. 2025 Mar-Apr;37(2):100735.
doi: 10.1016/j.arteri.2024.08.004. Epub 2024 Sep 28.

Elevated plasma levels of TNF-R1 predict the development of acute ischemic events in coronary patients with diabetes

[Article in English, Spanish]
Sebastián Mas-Fontao  1 , Nieves Tarín  2 , Carmen Cristóbal  3 , Manuel Soto-Catalán  4 , Ana Pello  5 , Alvaro Aceña  5 , Jairo Lumpuy-Castillo  4 , Carmen Garces  6 , Carmen Gomez-Guerrero  7 , Carlos Gutiérrez-Landaluce  8 , Luis M Blanco-Colio  9 , José Luis Martín-Ventura  10 , Ana Huelmos  11 , Joaquín Alonso  12 , Lorenzo López Bescós  13 , Juan A Moreno  14 , Ignacio Mahíllo-Fernández  15 , Óscar Lorenzo  7 , María Luisa González-Casaus  16 , Jesús Egido  17 , José Tuñón  18
Affiliations

Elevated plasma levels of TNF-R1 predict the development of acute ischemic events in coronary patients with diabetes

[Article in English, Spanish]
Sebastián Mas-Fontao et al. Clin Investig Arterioscler. 2025 Mar-Apr.

Abstract

Objectives: To examine the relationship between inflammatory biomarkers and the occurrence of cardiovascular events in patients with type 2 diabetes mellitus (DM2) and stable coronary artery disease.

Methods: A total of 964 patients with stable coronary artery disease were included. Plasma levels of inflammatory markers, including tumour necrosis factor receptors 1 and 2 (TNF-R1 and TNF-R2), growth differentiation factor-15 (GDF-15), soluble suppression of tumorigenicity 2 (sST2), and high-sensitivity C-reactive protein (hsCRP) were measured. The primary endpoint was the development of acute ischaemic events (any type of acute coronary syndrome, stroke, or transient ischaemic attack).

Results: There were 232 diabetic patients and 732 non-diabetic patients. Patients with coronary artery disease and DM2 (232, 24%) had higher levels of TNF-R1, TNF-R2, GDF-15, sST2 (P<.001), and hsCRP compared to patients without DM2, indicating a higher inflammatory state. After a median follow-up of 5.39 (2.81-6.92) years, patients with DM2 more frequently developed the primary endpoint (15.9% vs 10.8%; P=.035). Plasma levels of TNF-R1 were independent predictors of the primary endpoint in patients with DM2, along with male gender, triglyceride levels, and the absence of treatment with angiotensin-converting enzyme inhibitors. None of these inflammatory markers predicted the development of this event in non-diabetic patients.

Conclusions: Patients with stable coronary artery disease and DM2 exhibit elevated levels of the proinflammatory markers TNF-R1, TNF-R2, GDF-15, and sST2. Moreover, TNF-R1 is an independent predictor of acute ischaemic events only in diabetic patients.

Keywords: Biomarcadores inflamatorios; Cardiovascular prognosis; Coronary artery disease; Diabetes mellitus tipo 2; Enfermedad coronaria; Inflammatory biomarkers; Pronóstico cardiovascular; Receptor de TNF 1; TNF receptor 1; Type 2 diabetes mellitus.

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