Association of carotid artery atherosclerosis with circulating biomarkers of extracellular matrix remodeling: the Framingham Offspring Study.
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 (beta 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.
Romero
Jose R
JR
Department of Neurology, School of Medicine, Boston University, Boston, Massachusetts 02118-2526, USA.
Vasan
Ramachandran S
RS
Beiser
Alexa S
AS
Polak
Joseph F
JF
Benjamin
Emelia J
EJ
Wolf
Philip A
PA
Seshadri
Sudha
S
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000201:enzymology*; D016893:Carotid Stenosis / Q000097:blood* / Q000175:diagnosis* / Q000000981:diagnostic imaging; D015331:Cohort Studies; D018450:Disease Progression; D005109:Extracellular Matrix / Q000201:enzymology*; D005260:Female; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000097:blood* / Q000175:diagnosis* / Q000000981:diagnostic imaging; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D011347:Procollagen / Q000097:blood; D011379:Prognosis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000201:enzymology / Q000473:pathology; D014463:Ultrasonography
D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; D019715:Tissue Inhibitor of Metalloproteinase-1; C041876:procollagen Type III-N-terminal peptide; D020780:Matrix Metalloproteinase 9