Serum Tenascin-C is independently associated with increased major adverse cardiovascular events and death in patients with type II diabetes

Abstract

Tenascin-C (TNC) is an extracellular matrix glycoprotein highly expressed in inflammatory and cardiovascular (CV) pathologies. In heart failure or after myocardial infarction, elevated TNC is associated with adverse outcomes. Serum TNC has not yet been studied specifically in patients with type II diabetes, a condition associated with chronic low-grade inflammation and increased CV risk. We hypothesized that high serum TNC measured at enrolment in a large cohort of type II diabetic patients is associated with major adverse CV events (MACE) and death during follow-up. A prospective, monocentric cohort of consecutive type 2 diabetes patients (the SURDIAGENE cohort; total of 1338 patients; 58% men, mean ± SD age 64 ± 11 years) was followed for a median of 89 months for death as primary endpoint and MACE (i.e. CV death, myocardial infarction or stroke) as a secondary endpoint. Patients with stage ≥ 4 renal disease were excluded. During follow-up, 448 patients (representing 4.4% of the total person-years) died and 506 patients (representing 5.2% of the total person-years) presented with MACE. Cox multivariate analysis showed that increased serum TNC concentrations were significantly associated with death (HR per 10 ng/mL: 1.03 (1.01–1.05) P = 0.0095) and MACE (HR per 10 ng/mL: 1.02 (1.00–1.04) P = 0.0162), after adjustment for sex, age, established modifiable CV risk factors (active smoking, hypertension, hypercholesterolemia) and NT-proBNP levels. In patients with type 2 diabetes, we show for the first time that increased serum TNC concentrations are independently associated with MACE and death. These findings suggest that elevated TNC expression might be implicated in the increased CV risk associated with diabetes, and might be useful for CV risk stratification in this context.