Prospective associations of circulating thrombospondin-2 level with heart failure hospitalization, left ventricular remodeling and diastolic function in type 2 diabetes

BACKGROUND: Circulating thrombospondin-2 (TSP2) levels were associated with the development of heart failure (HF) in recent studies. However, these studies included only a minority of patients with type 2 diabetes, which is associated with an increased HF risk. As hyperglycemia induces TSP2 expression and its tissue expression increases in type 2 diabetes, we investigated the prospective association of circulating TSP2 with incident HF hospitalization (HHF), and its associations with longitudinal changes of echocardiographic parameters in type 2 diabetes. METHODS: Baseline serum TSP2 levels were measured in 4949 patients with type 2 diabetes to determine its association with incident HHF using multivariable Cox regression analysis. In the echocardiographic study, baseline serum TSP2 levels were measured in another 146 patients with type 2 diabetes but without cardiovascular diseases who underwent detailed transthoracic echocardiography at baseline and after 1 year. RESULTS: Over a median follow-up of 7.8 years, 330 of 4949 patients (6.7%) developed incident HHF. Baseline serum TSP2 levels were independently associated with the development of HHF (HR 1.31, 95%CI 1.06-1.62, p = 0.014) after adjustments for baseline conventional cardiovascular risk factors, atrial fibrillation, estimated glomerular filtration rate, albuminuria and high-sensitivity C-reactive protein level, use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, loop-diuretics, aspirin, insulin, metformin and sodium-glucose co-transporter 2 inhibitors. Moreover, baseline serum TSP2 levels were independently associated with increase in average E/e' and left atrial volume index (p = 0.04 and < 0.01, respectively). CONCLUSION: Serum TSP2 levels were independently associated with both incident HHF and deterioration in diastolic function in type 2 diabetes. TRIAL REGISTRATION: Not Applicable.