Circulating angiopoietin-2, its soluble receptor Tie-2, and mortality in the general population

Aims: To assess the association of circulating concentrations of angiopoietin-2 (Ang-2) and its soluble receptor Tie-2 (sTie-2) with all-cause, cardiovascular, and cancer mortality in a population-based sample.

Methods and results: Angiopoietin-2 and sTie-2 were measured in 3220 participants (1665 women; mean age 54.4 years) in the Study of Health in Pomerania (SHIP). Multivariable adjusted hazard ratios (HRs) for mortality were estimated using Cox proportional hazard models. During a median follow-up of 6.2 years, 217 participants died. Ang-2 levels were positively associated with all-cause mortality [HR 1.29; 95% confidence interval (CI) 1.19-1.39 per 1 SD increment; P < 0.001] and cardiovascular mortality (HR 1.32; 95% CI 1.18-1.49; P < 0.001), but not with cancer mortality (HR 1.08; 95% CI 0.89-1.32; P = 0.416). Levels of sTie-2 were not significantly related to all-cause mortality (HR 1.12; 95% CI 0.98-1.27; P = 0.102). Adding Ang-2 to a prediction model for all-cause mortality with standard risk factors slightly improved discrimination (Δ Harrell's C, 0.008; P < 0.001) but not risk reclassification (continuous net reclassification improvement, -0.015; P = 0.571).

Conclusion: In our community-based sample, higher serum Ang-2 concentrations were associated with greater risk for all-cause and cardiovascular mortality, suggesting that subtle increases in Ang-2 levels might reflect processes such as vascular remodelling that are associated with higher mortality risk. Adding Ang-2 to a mortality prediction model only modestly improved discrimination.