TIMP-1 - A marker of left ventricular diastolic dysfunction and fibrosis in hypertension

被引:163
作者
Lindsay, MM
Maxwell, P
Dunn, FG
机构
[1] Stobhill Gen Hosp, Dept Cardiol, Glasgow G21 3UW, Lanark, Scotland
[2] Stobhill Gen Hosp, Dept Biochem, Glasgow G21 3UW, Lanark, Scotland
关键词
hypertension; essential; hypertrophy; diastole; collagen; fibrosis;
D O I
10.1161/01.HYP.0000024573.17293.23
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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 μg/L versus 2.9 μg/L, P < 0.001), and PICP (200 mug/L versus 166 mug/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 market of fibrosis.
引用
收藏
页码:136 / 141
页数:6
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