Thrombospondin-2 as a Potential Risk Factor in a General Population

Int Heart J. 2019 Mar 20;60(2):310-317. doi: 10.1536/ihj.18-246. Epub 2019 Feb 8.


Serum thrombospondin-2 (TSP-2) is a glycoprotein expressed in the extracellular matrix (ECM), which increases during tissue remodeling. It has been shown in recent studies that TSP-2 is a useful predictor of cardiovascular death in patients with heart failure (HF). However, the clinical importance of serum TSP-2 levels in a general population is still unknown. Therefore, we aimed to clarify the association between TSP-2 and clinical risk factors. A periodic epidemiological survey was performed in a community dwelling in the town of Uku, Nagasaki, Japan. A total of 445 residents received a health checkup examination including blood tests such as fasting serum levels of TSP-2. Uni- and multivariate analyses were performed to examine the relationship between TSP-2 and clinical risk factors. All statistical analyses were performed using SAS v9.4 program. The mean ± standard deviation of age was 67.0 ± 9.4 years old. Although serum TSP-2 levels (mean: 20.9 ± 8.5 ng/mL) showed no significant sex difference, they were significantly correlated with the levels of plasma glucose (P < 0.001), insulin (P < 0.01), homeostasis model assessment of insulin resistance (HOMA-IR) (P < 0.001), estimated glomerular filtration rate (eGFR) (P < 0.01, inversely), high-sensitivity C-reactive protein (hs-CRP) (P < 0.001), history of atrial fibrillation (P < 0.001), history of cardiovascular diseases (P < 0.001), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (P < 0.001). Moreover, in the multiple stepwise linear regression analysis, the levels of TSP-2 were independently and significantly associated with the history of atrial fibrillation (P < 0.0001), HOMA-IR (P < 0.001), high-sensitivity CRP (P = 0.011), and NT-proBNP (P = 0.043). These results indicated the significant relationship between TSP-2 and clinical risk factors in a general population, suggesting its role as a predictor of heart disease morbidity and mortality.

Keywords: Epidemiology; TSP-2.

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Glucose / analysis
  • C-Reactive Protein / analysis*
  • Cardiovascular Diseases* / blood
  • Cardiovascular Diseases* / epidemiology
  • Correlation of Data
  • Female
  • Glomerular Filtration Rate
  • Health Surveys
  • Homeostasis
  • Humans
  • Insulin / blood
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Risk Assessment / methods
  • Risk Factors
  • Thrombospondins / blood*


  • Biomarkers
  • Blood Glucose
  • Insulin
  • Peptide Fragments
  • Thrombospondins
  • pro-brain natriuretic peptide (1-76)
  • thrombospondin 2
  • Natriuretic Peptide, Brain
  • C-Reactive Protein