title: TIMP-1: a marker of left ventricular diastolic dysfunction and fibrosis in hypertension.
abstract: This study was designed to document noninvasively the pathological mechanisms responsible for myocardial fibrosis and to assess the clinical utility of plasma markers of collagen synthesis and degradation as screening tools for the assessment of fibrosis in hypertension. We studied 100 never-treated hypertensive patients and 50 normal subjects. Echocardiographic assessment was made of left ventricular (LV) mass and diastolic filling using measurement of E:A ratio, E wave deceleration time (E dec), and isovolumic relaxation time (IVRT). The presence of diastolic dysfunction was taken as a surrogate marker for the presence of myocardial fibrosis. Plasma carboxy-terminal propeptide of collagen type I (PICP), carboxy-terminal telopeptide of collagen type I (CITP), and tissue inhibitor of matrix metalloproteinases type I (TIMP-1) were measured as markers of collagen synthesis, degradation, and inhibition of degradation, respectively. Plasma TIMP-1 was significantly elevated in the hypertensive cohort (358 ng/mL versus 253 ng/mL, P<0.001) as were CITP (5.2 microg/L versus 2.9 microg/L, P<0.001), and PICP (200 microg/L versus 166 microg/L, P<0.05). TIMP-1 was significantly elevated in patients with diastolic dysfunction (421 ng/mL versus 283 ng/mL P<0.01) and correlated with markers of diastolic filling, namely E:A ratio (r=0.26, P<0.05) and E Dec (r=0.41, P<0.01). A plasma TIMP-1 level of >500 ng/mL had a specificity of 97% and a positive predictive value of 96% in predicting diastolic dysfunction. In patients with untreated hypertension, there is evidence of increased collagen synthesis, degradation, and inhibition of degradation resulting in fibrosis. Our results demonstrate that plasma TIMP-1 correlates with markers of LV diastolic filling, is predictive of LV dysfunction, and is a potential noninvasive marker of fibrosis.
authors.affiliation: Department of Cardiology, Stobhill Hospital, Glasgow, Scotland, United Kingdom. mooja@mooja.demon.co.uk
authors.forename: M Mitchell
authors.initials: MM
authors.lastname: Lindsay
authors.forename: Paul
authors.initials: P
authors.lastname: Maxwell
authors.forename: Francis G
authors.initials: FG
authors.lastname: Dunn
mesh_terms: D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D015331:Cohort Studies; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D005355:Fibrosis; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011237:Predictive Value of Tests; D011347:Procollagen / Q000097:blood; D012083:Renin / Q000097:blood; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D019715:Tissue Inhibitor of Metalloproteinase-1; C052929:collagen type I trimeric cross-linked peptide; C042813:procollagen type I carboxy terminal peptide; D000450:Aldosterone; D003094:Collagen; D012083:Renin