Association of Plasma Angiotensin-(1–7) Level and Left Ventricular Function in Patients with Type 2 Diabetes Mellitus

BACKGROUND We recently found that overexpression of angiotensin (Ang)-converting enzyme 2, which metabolizes Ang-II to Ang-(1-7) and Ang-I to Ang-(1-9), may prevent diabetes-induced left ventricular remodeling and dysfunction in rats. Our objective was to evaluate the association of plasma Ang-(1-7) level and left ventricular function in patients with type 2 diabetes mellitus. METHODOLOGY/PRINCIPAL FINDINGS We measured the left ventricular ejection fraction (EF), ratio of early to late left ventricular filling velocity (E/A) and ratio of early diastolic mitral inflow to annular velocity (E/Ea) by ultrasonography in 110 patients with type 2 diabetes mellitus for more than 5 years. Anthropometric and fasting blood values were obtained from medical records. The plasma Ang-(1-7) level in patients with a poor EF (<50%) was significantly lower than that in patients with EF ≥50%; the level in patients with E/A <1 was significantly lower than that in patients with E/A ≥1; and the level in patients with E/Ea >15 was significantly lower than that in patients with E/Ea ≤15. Ang-(1-7) level was negatively correlated with E/Ea and Log-N-terminal pro-B-type natriuretic peptide and positively with EF and E/A. Stepwise multiple regression analysis revealed that Ang-(1-7), hemoglobin A1c and Ang-II levels as well as duration of diabetes predicted EF; Ang-(1-7) level, fasting blood glucose, low-density lipoprotein cholesterol level and duration of diabetes predicted E/A; and Ang-(1-7) and hemoglobin A1c levels predicted E/Ea. CONCLUSIONS/SIGNIFICANCE Plasma Ang-(1-7) level is independently associated with left ventricular function in patients with type 2 diabetes mellitus and may be a biomarker for assessing cardiac function in such patients.