TY - JOUR
T1 - Tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9 levels in patients with hypertension
T2 - Relationship to tissue Doppler indices of diastolic relaxation
AU - Tayebjee, Muzahir H.
AU - Nadar, Sunil K.
AU - MacFadyen, Robert J.
AU - Lip, Gregory Y.H.
N1 - Funding Information:
This study was supported by the City Hospital Research & Development Programme for the Haemostasis Thrombosis and Vascular Biology Unit.
PY - 2004/9
Y1 - 2004/9
N2 - 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. 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. 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). 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.
AB - 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. 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. 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). 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.
KW - Extracellular matrix
KW - echocardiography
KW - hypertension
KW - matrix metalloproteinase-9
KW - tissue Doppler
KW - tissue inhibitor of metalloproteinase-1
UR - http://www.scopus.com/inward/record.url?scp=4444292589&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4444292589&partnerID=8YFLogxK
U2 - 10.1016/S0895-7061(04)00902-1
DO - 10.1016/S0895-7061(04)00902-1
M3 - Article
C2 - 15363818
AN - SCOPUS:4444292589
SN - 0895-7061
VL - 17
SP - 770
EP - 774
JO - American Journal of Hypertension
JF - American Journal of Hypertension
IS - 9
ER -