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TIMP-1: a marker of left ventricular diastolic dysfunction and fibrosis in hypertension
M Mitchell Lindsay1, Paul Maxwell, Francis G Dunn
1Department of Cardiology, Stobhill Hospital, Glasgow, Scotland, United Kingdom. mooja@mooja.demon.co.uk
Insights
Plasma tissue inhibitor of matrix metalloproteinases type I (TIMP-1) is a promising noninvasive marker for detecting myocardial fibrosis in hypertension. Elevated TIMP-1 levels accurately predict left ventricular diastolic dysfunction, aiding in fibrosis assessment.
Area of Science:
- Cardiology
- Biochemistry
- Pathophysiology
Background:
- Hypertension is associated with myocardial fibrosis, a condition impacting cardiac function.
- Assessing myocardial fibrosis noninvasively is crucial for managing hypertensive heart disease.
- Existing methods for fibrosis assessment can be invasive or lack comprehensive utility.
Purpose of the Study:
- To investigate the pathological mechanisms of myocardial fibrosis in hypertension.
- To evaluate plasma markers of collagen metabolism as noninvasive tools for fibrosis screening.
- To assess the clinical utility of plasma tissue inhibitor of matrix metalloproteinases type I (TIMP-1) in predicting diastolic dysfunction.
Main Methods:
- Studied 100 never-treated hypertensive patients and 50 controls.
- Performed echocardiography to assess left ventricular (LV) mass and diastolic filling (E:A ratio, E wave deceleration time, IVRT).
- Measured plasma levels of collagen synthesis (PICP), degradation (CITP), and inhibition of degradation (TIMP-1) markers.
Main Results:
- Hypertensive patients showed elevated plasma PICP, CITP, and TIMP-1 compared to controls.
- Plasma TIMP-1 was significantly higher in patients with diastolic dysfunction.
- TIMP-1 levels correlated with diastolic filling parameters (E:A ratio, E Dec) and predicted diastolic dysfunction with high specificity (97%) and PPV (96%).
Conclusions:
- Untreated hypertension involves increased collagen synthesis, degradation, and inhibition, leading to myocardial fibrosis.
- Plasma TIMP-1 is a potential noninvasive biomarker for myocardial fibrosis in hypertension.
- TIMP-1 effectively correlates with LV diastolic function and predicts LV dysfunction.
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.