title: Tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9 levels in patients with hypertension Relationship to tissue Doppler indices of diastolic relaxation.
abstract: BACKGROUND
  Hypertension, hypertensive heart disease, and left ventricular (LV) hypertrophy are integral to symptomatic diastolic heart failure. Tissue inhibitor of metalloproteinase-1 (TIMP-1) is linked to extracellular matrix fibrosis and is elevated in hypertension. We hypothesized a link between circulating TIMP-1, matrix metalloproteinase-9 (MMP-9), and resting echocardiographic LV filling parameters using tissue Doppler parameters of diastolic (dys)function.
  
  
  METHODS
  Circulating MMP-9 and TIMP-1 levels were measured in citrated plasma by ELISA in 74 patients with hypertension (58 men, mean age 58 +/- 11 years) and 34 controls (23 men, mean age 53 +/- 13 years). All had confirmed normal short axis systolic contractility, with no significant wall motion abnormalities; the LV mass and standard resting tissue Doppler echocardiographic indices of diastolic function were also recorded.
  
  
  RESULTS
  Both MMP-9 and TIMP-1 levels were higher in the hypertensive group (P =.0039 and P =.0054, respectively). When compared to controls, hypertensive patients had a greater LV mass (P =.0054), and differences in many of the parameters reflecting diastolic dysfunction (controls versus hypertensives: E: 0.71 +/- 0.15 v 0.81 +/- 0.15 m/sec, P =.004; A: 0.66 +/- 0.12 v 0.81 +/- 0.16 m/sec, P <.0001; e': 0.12 (0.09-0.14) v 0.09 (0.07-0.10) m/sec, P =.0017; e'/a': 1.20 (1.00-1.80) v 0.88 (0.71-1.05), P <.0001; E/e': 6.54 (4.75-7.14) v 8.89 (7.55-10.75), P <.0001, respectively). Within the hypertensive cohort, only TIMP-1 levels correlated with LV mass (r = 0.271, P =.024), LV mass index (r = 0.323, P =.007), and tissue Doppler parameters of diastolic dysfunction, including e' (r = -0.338, P =.005), a' (r = -0.350, P =.005), and E/e' (r = 0.334, P =.005).
  
  
  CONCLUSIONS
  TIMP-1 is thought to increase tissue concentrations of collagen type I by preventing its breakdown by MMPs. Our findings therefore add weight to a hypothesis suggesting that TIMP-1 may be a key mediator of LV diastolic dysfunction through definition of ventricular matrix composition.
authors.affiliation: Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, United Kingdom.
authors.forename: Muzahir H
authors.initials: MH
authors.lastname: Tayebjee
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Nadar
authors.forename: Robert J
authors.initials: RJ
authors.lastname: MacFadyen
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D003971:Diastole; D015150:Echocardiography, Doppler; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D013599:Systole; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000378:metabolism*
chemical_list: D000959:Antihypertensive Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9