title: Tissue inhibitor of metalloproteinse-1 is a marker of diastolic dysfunction using tissue doppler in patients with type 2 diabetes and hypertension.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: City Hospital, Birmingham, UK.
authors.forename: M H
authors.initials: MH
authors.lastname: Tayebjee
authors.forename: H S
authors.initials: HS
authors.lastname: Lim
authors.forename: S
authors.initials: S
authors.lastname: Nadar
authors.forename: R J
authors.initials: RJ
authors.lastname: MacFadyen
authors.forename: G Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging; D003971:Diastole; D018619:Echocardiography, Doppler, Pulsed; D005260:Female; D006331:Heart Diseases / Q000150:complications / Q000000981:diagnostic imaging*; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1