Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in hypertension and their relationship to cardiovascular risk and treatment

A substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)

Muzahir H. Tayebjee, Sunil Nadar, Andrew D. Blann, D. Gareth Beevers, Robert J. MacFadyen, Gregory Y H Lip

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

Hypertension results in structural changes to the cardiac and vascular extracellular matrix (ECM). Matrix metalloproteinases (MMP) and their inhibitors (TIMP) may play a central role in the modulation of this matrix. We hypothesized that both MMP-9 and TIMP-1 would be abnormal in hypertension, reflecting alterations in ECM turnover, and that their circulating levels should be linked to cardiovascular (CHD) and stroke (CVA) risk scores using the Framingham equation. Second, we hypothesized that treatment would result in changes in ECM indices. Plasma MMP-9 and TIMP-1 were measured before and after treatment (median 3 years) from 96 patients with uncontrolled hypertension participating in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Pretreatment values were compared to circulating MMP-9 and TIMP-1 levels in 45 age- and sex-matched healthy controls. Circulating pretreatment MMP-9 and TIMP-1 levels were significantly higher in patients with hypertension than in the normotensive controls (P =. 0041 and P =. 0166, respectively). Plasma MMP-9 levels decreased, and TIMP-1 levels increased after treatment (P =. 035 and P =. 005, respectively). Levels of MMP-9 correlated with CHD risk (r = 0.317, P =. 007) and HDL cholesterol (r = -0.237, P =. 022), but not CVA risk. There were no significant correlations between TIMP-1 and CVA or CHD scores. Increased circulating MMP-9 and TIMP-1 at baseline in patients with hypertension could reflect an increased deposition and retention of type I collagen at the expense of other components of ECM within the cardiac and vascular ECM. After cardiovascular risk management, MMP-9 levels decreased and TIMP-1 levels increased. Elevated levels of MMP-9 also appeared to be associated with higher Framingham cardiovascular risk scores. Our observations suggest a possible role for these surrogate markers of tissue ECM composition and the prognosis of cardiovascular events in hypertension.

Original languageEnglish
Pages (from-to)764-769
Number of pages6
JournalAmerican Journal of Hypertension
Volume17
Issue number9
DOIs
Publication statusPublished - Sep 2004

Fingerprint

Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinase 9
Hypertension
Extracellular Matrix
Therapeutics
Blood Vessels
Risk Management
Collagen Type I
HDL Cholesterol
Biomarkers
Myocardial Infarction

Keywords

  • Extracellular matrix
  • Framingham risk score
  • hypertension
  • matrix metalloproteinase-9
  • tissue inhibitor of metalloproteinase-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in hypertension and their relationship to cardiovascular risk and treatment : A substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). / Tayebjee, Muzahir H.; Nadar, Sunil; Blann, Andrew D.; Gareth Beevers, D.; MacFadyen, Robert J.; Lip, Gregory Y H.

In: American Journal of Hypertension, Vol. 17, No. 9, 09.2004, p. 764-769.

Research output: Contribution to journalArticle

@article{7dd7f60d46ab4815b6425fc316eb1f10,
title = "Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in hypertension and their relationship to cardiovascular risk and treatment: A substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)",
abstract = "Hypertension results in structural changes to the cardiac and vascular extracellular matrix (ECM). Matrix metalloproteinases (MMP) and their inhibitors (TIMP) may play a central role in the modulation of this matrix. We hypothesized that both MMP-9 and TIMP-1 would be abnormal in hypertension, reflecting alterations in ECM turnover, and that their circulating levels should be linked to cardiovascular (CHD) and stroke (CVA) risk scores using the Framingham equation. Second, we hypothesized that treatment would result in changes in ECM indices. Plasma MMP-9 and TIMP-1 were measured before and after treatment (median 3 years) from 96 patients with uncontrolled hypertension participating in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Pretreatment values were compared to circulating MMP-9 and TIMP-1 levels in 45 age- and sex-matched healthy controls. Circulating pretreatment MMP-9 and TIMP-1 levels were significantly higher in patients with hypertension than in the normotensive controls (P =. 0041 and P =. 0166, respectively). Plasma MMP-9 levels decreased, and TIMP-1 levels increased after treatment (P =. 035 and P =. 005, respectively). Levels of MMP-9 correlated with CHD risk (r = 0.317, P =. 007) and HDL cholesterol (r = -0.237, P =. 022), but not CVA risk. There were no significant correlations between TIMP-1 and CVA or CHD scores. Increased circulating MMP-9 and TIMP-1 at baseline in patients with hypertension could reflect an increased deposition and retention of type I collagen at the expense of other components of ECM within the cardiac and vascular ECM. After cardiovascular risk management, MMP-9 levels decreased and TIMP-1 levels increased. Elevated levels of MMP-9 also appeared to be associated with higher Framingham cardiovascular risk scores. Our observations suggest a possible role for these surrogate markers of tissue ECM composition and the prognosis of cardiovascular events in hypertension.",
keywords = "Extracellular matrix, Framingham risk score, hypertension, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1",
author = "Tayebjee, {Muzahir H.} and Sunil Nadar and Blann, {Andrew D.} and {Gareth Beevers}, D. and MacFadyen, {Robert J.} and Lip, {Gregory Y H}",
year = "2004",
month = "9",
doi = "10.1016/j.amjhyper.2004.05.019",
language = "English",
volume = "17",
pages = "764--769",
journal = "American Journal of Hypertension",
issn = "0895-7061",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in hypertension and their relationship to cardiovascular risk and treatment

T2 - A substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)

AU - Tayebjee, Muzahir H.

AU - Nadar, Sunil

AU - Blann, Andrew D.

AU - Gareth Beevers, D.

AU - MacFadyen, Robert J.

AU - Lip, Gregory Y H

PY - 2004/9

Y1 - 2004/9

N2 - Hypertension results in structural changes to the cardiac and vascular extracellular matrix (ECM). Matrix metalloproteinases (MMP) and their inhibitors (TIMP) may play a central role in the modulation of this matrix. We hypothesized that both MMP-9 and TIMP-1 would be abnormal in hypertension, reflecting alterations in ECM turnover, and that their circulating levels should be linked to cardiovascular (CHD) and stroke (CVA) risk scores using the Framingham equation. Second, we hypothesized that treatment would result in changes in ECM indices. Plasma MMP-9 and TIMP-1 were measured before and after treatment (median 3 years) from 96 patients with uncontrolled hypertension participating in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Pretreatment values were compared to circulating MMP-9 and TIMP-1 levels in 45 age- and sex-matched healthy controls. Circulating pretreatment MMP-9 and TIMP-1 levels were significantly higher in patients with hypertension than in the normotensive controls (P =. 0041 and P =. 0166, respectively). Plasma MMP-9 levels decreased, and TIMP-1 levels increased after treatment (P =. 035 and P =. 005, respectively). Levels of MMP-9 correlated with CHD risk (r = 0.317, P =. 007) and HDL cholesterol (r = -0.237, P =. 022), but not CVA risk. There were no significant correlations between TIMP-1 and CVA or CHD scores. Increased circulating MMP-9 and TIMP-1 at baseline in patients with hypertension could reflect an increased deposition and retention of type I collagen at the expense of other components of ECM within the cardiac and vascular ECM. After cardiovascular risk management, MMP-9 levels decreased and TIMP-1 levels increased. Elevated levels of MMP-9 also appeared to be associated with higher Framingham cardiovascular risk scores. Our observations suggest a possible role for these surrogate markers of tissue ECM composition and the prognosis of cardiovascular events in hypertension.

AB - Hypertension results in structural changes to the cardiac and vascular extracellular matrix (ECM). Matrix metalloproteinases (MMP) and their inhibitors (TIMP) may play a central role in the modulation of this matrix. We hypothesized that both MMP-9 and TIMP-1 would be abnormal in hypertension, reflecting alterations in ECM turnover, and that their circulating levels should be linked to cardiovascular (CHD) and stroke (CVA) risk scores using the Framingham equation. Second, we hypothesized that treatment would result in changes in ECM indices. Plasma MMP-9 and TIMP-1 were measured before and after treatment (median 3 years) from 96 patients with uncontrolled hypertension participating in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Pretreatment values were compared to circulating MMP-9 and TIMP-1 levels in 45 age- and sex-matched healthy controls. Circulating pretreatment MMP-9 and TIMP-1 levels were significantly higher in patients with hypertension than in the normotensive controls (P =. 0041 and P =. 0166, respectively). Plasma MMP-9 levels decreased, and TIMP-1 levels increased after treatment (P =. 035 and P =. 005, respectively). Levels of MMP-9 correlated with CHD risk (r = 0.317, P =. 007) and HDL cholesterol (r = -0.237, P =. 022), but not CVA risk. There were no significant correlations between TIMP-1 and CVA or CHD scores. Increased circulating MMP-9 and TIMP-1 at baseline in patients with hypertension could reflect an increased deposition and retention of type I collagen at the expense of other components of ECM within the cardiac and vascular ECM. After cardiovascular risk management, MMP-9 levels decreased and TIMP-1 levels increased. Elevated levels of MMP-9 also appeared to be associated with higher Framingham cardiovascular risk scores. Our observations suggest a possible role for these surrogate markers of tissue ECM composition and the prognosis of cardiovascular events in hypertension.

KW - Extracellular matrix

KW - Framingham risk score

KW - hypertension

KW - matrix metalloproteinase-9

KW - tissue inhibitor of metalloproteinase-1

UR - http://www.scopus.com/inward/record.url?scp=4444286972&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4444286972&partnerID=8YFLogxK

U2 - 10.1016/j.amjhyper.2004.05.019

DO - 10.1016/j.amjhyper.2004.05.019

M3 - Article

VL - 17

SP - 764

EP - 769

JO - American Journal of Hypertension

JF - American Journal of Hypertension

SN - 0895-7061

IS - 9

ER -