Tissue inhibitor of metalloproteinse-1 is a marker of diastolic dysfunction using tissue doppler in patients with type 2 diabetes and hypertension

Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) is associated with increased fibrosis of the extracellular matrix (ECM). Myocardial stiffness is a feature of diastolic dysfunction. We assessed circulating TIMP-1 as a marker of diastolic dysfunction in patients with type 2 diabetes mellitus (DM) and hypertension, who were compared with healthy controls. Methods: We recruited 54 patients (43 males; mean age 68 ± 5 years) with treated type 2 DM (i.e. controlled glycaemia, hypertension, hyperlipidaemia), 35 (30 males; 69 ± 8 years) treated nondiabetic hypertensives, and 31 healthy controls (18 males; 66 ± 5 years). Circulating TIMP-1 was measured by ELISA. Using transthoracic echocardiography, the early (E) diastolic mitral inflow velocity was measured with pulse wave Doppler, and the early mitral annular velocity (e′), a recognized index of diastolic relaxation, was measured with tissue Doppler. The E/A ratio was also calculated and isovolumic relaxation time measured. Results: Mean e′ levels differed significantly between controls, diabetics and hypertensives (P < 0.0001). Circulating TIMP-1 was significantly different between patients and controls (P = 0.006), but there was no statistically significant difference between the DM and hypertension group. In both groups, only e′ was negatively correlated with TIMP-1 levels, with a stronger correlation among the hypertensive patients (Spearman r = -0.544, P= 0.001) when compared with the diabetic group (r = -0.341, P = 0.011). Conclusion: Diastolic relaxation is impaired in diabetes and hypertensive patients. The relationship between TIMP-1 and e′ may reflect increased myocardial fibrosis and consequent diastolic dysfunction, which may be more prominent in hypertension.