Elevated serum S100A12 levels are associated with increased risk of heart failure in patients with type 2 diabetes: the SURDIAGENE prospective study

The hyperglycemic stress induces the release of inflammatory proteins such as S100A12, one of the endogenous ligands of the receptors for advanced glycation end products (RAGE). Chronic activation of RAGE favors vascular disease and cardiac dysfunction. The aim of our study was to investigate the prognostic value of circulating S100A12 for predicting major adverse cardiovascular events (MACE) and acute heart failure (AHF) in patients with type 2 diabetes (T2D) beyond established cardiovascular (CV) risk factors. Serum S100A12 levels were measured at baseline in T2D patients recruited in the SURDIAGENE prospective cohort. Outcomes were defined as occurrence of AHF requiring hospitalization, MACE and all-cause death. We used a proportional hazard model, and adjustments were performed for established CV risk factors. Among 1345 patients, 210 developed AHF, 505 MACE, and 446 died during a median follow-up of 84 months. Baseline serum S100A12 levels were associated with an increased risk of AHF (HR [95%CI] 1.28 [1.01-1.62], P = 0.0436), but neither death ( P = 0.1658) nor MACE ( P = 0.600). After adjustment for CV risk factors, S100A12 levels remained significantly associated with an increased risk of AHF (HR = 1.29 [1.01-1.65], P = 0.0422). After exclusion of 217 patients with basal NT-proBNP levels > 450 pg/ml suggesting pre-existing chronic HF, the predictive value of baseline serum S100A for future AHF events tended to be more significant (HR = 1.45 [1.06-1.97], P = 0.0202). In patients with T2D, increased serum S100A12 levels are independently associated with risk of future AHF events, but neither with risk of MACE nor death.