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

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Abstract
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.