Association of Carotid Artery Atherosclerosis With Circulating Biomarkers of Extracellular Matrix Remodeling: The Framingham Offspring Study

Jose R. Romero, Ramachandran S. Vasan, Alexa S. Beiser, Joseph F. Polak, Emelia J. Benjamin, Philip A. Wolf, Sudha Seshadri

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Objective: We sought to relate circulating biomarkers of extracellular matrix turnover to site-specific measures of carotid artery atherosclerosis on duplex ultrasound. Background: Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) regulate extracellular matrix remodeling, a key feature of atherosclerosis, and their circulating concentrations can be assayed. MMP-9, TIMP-1, and protocollagen-III n-terminal propeptide (PIIINP) may relate differentially to the severity of atherosclerosis at different carotid artery sites. However, data examining this premise are sparse. Methods: We related circulating MMP-9, TIMP-1, and/or PIIINP concentrations to carotid atherosclerosis on duplex ultrasound in 1006 Framingham offspring (mean age 58 years, 56% women) who attended a routine examination from 1995 to 1998. We used multivariable regression to relate MMP-9 (detectable v undetectable), TIMP-1, and PIIINP (age- and sex-specific quartiles) to internal carotid artery (IC) stenosis (>25%) and log-transformed common carotid artery and IC intima-media thickness (IMT). Results: Detectable MMP-9 was associated with carotid stenosis (odds ratio [OR] 1.71, P = .032) but not with IMT. Higher TIMP-1 was associated with carotid stenosis (OR for Quartiles (Q)4 v Q1-3, 1.63, P = .022) and a higher IC IMT (β 0.057 ± 0.025, Q4 v Q1-3, P = .023). Higher PIIINP (Q4 v Q1-3) showed a borderline association with carotid stenosis (OR 1.45 for Q4 v Q1-3, P = .095) but not with IMT. TIMP-1 was not associated with common carotid artery IMT. Conclusions: In our community-based sample of middle-aged to older adults, higher circulating biomarkers of matrix remodeling were associated with a greater prevalence of carotid stenosis and subclinical atherosclerosis in the IC. Our findings are consistent with regional differences in matrix remodeling in the carotid artery.

Original languageEnglish (US)
Pages (from-to)412-417
Number of pages6
JournalJournal of Stroke and Cerebrovascular Diseases
Issue number6
StatePublished - Nov 2008
Externally publishedYes


  • Carotid artery
  • atherosclerosis
  • intima media thickness
  • matrix proteins
  • stenosis

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Rehabilitation
  • Surgery


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