Higher Tenascin-C Levels Associated with Cardiovascular Disease

Studies have shown that the extracellular matrix glycoprotein tenascin-C (TN-C) is transiently upregulated at sites of inflammation (e.g., after acute myocardial infarction), and as such, it is generally considered a marker of inflammation in CV diseases. Serum TN-C has not yet been specifically studied in individuals with type 2 diabetes, which is a condition associated with chronic low-grade inflammation and increased CV disease risk.

Scientists at the ELSAN, Polyclinique de Poitiers (Poitiers, France) and their many colleagues used a prospective, monocentric cohort of consecutive type 2 diabetes participants (the SURDIAGENE cohort) with all-cause death as a primary endpoint and MACE (CV death, non-fatal myocardial infarction or stroke) as a secondary endpoint. They used a proportional hazard model after adjustment for traditional risk factors and the relative integrated discrimination improvement (rIDI) to assess the incremental predictive value of TN-C for these risk factors.

The average age of the included individuals was 64 ± 11 years. Patients with a baseline estimated glomerular filtration rate <30 mL/min/1.73 m², a history of prior renal replacement therapy, or a follow-up duration of <3 months were excluded. Blood samples and second morning urine samples were obtained from individuals after an overnight fast to measure various biological characteristics, such as hemoglobin A1c, low-density lipoprotein cholesterol, serum creatinine, and TN-C levels.

The team reported that higher TN-C concentrations were significantly associated with older age, longer duration of diabetes, history of CV disease, and diabetic retinopathy severity. Median follow-up duration was 89 months (range, 57-130 months), corresponding to 9,965 person-years. The overall mortality rate was 4.4% of total person-years of follow-up duration and the MACE rate was 5.2% of total person-years. The most common cause of death was CV diseases (54%). Baseline serum TN-C concentrations were higher in the group of individuals who died compared with survivors (89.3 ± 49.8 versus 69.0 ± 38.1 ng/mL) and higher in individuals with versus without incidental MACE (87.2 ± 48.4 versus 68.9 ± 38.6 ng/mL).

This study showed that higher serum TN-C concentrations were significantly associated with an increased risk for mortality and MACE in type 2 diabetes, even after adjustment for inflammatory markers such as angiopoietin-like 2 and tumor necrosis factor receptor 1 (TNFR1). The authors concluded that TN-C showed a significant predictive value not only for all-cause death, but also for MACE, suggesting that TN-C overexpression in individuals with type 2 diabetes may be linked to CV disease development and progression. The study was published ahead of print on February 10, 2020 in the journal Diabetologia.

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ELSAN, Polyclinique de Poitiers