To relate circulating biomarkers of extracellular matrix (ECM) turnover to site-specific measures of carotid artery atherosclerosis on duplex ultrasound.
Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) regulate ECM 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.
We related circulating MMP-9, TIMP-1 and/or PIIINP concentrations to carotid atherosclerosis on duplex ultrasound in1006 Framingham Offspring (mean age 58 years, 56% women) who attended a routine examination from 1995–1998. We used multivariable regression to relate MMP-9 (detectable versus undetectable), and TIMP-1 and PIIINP (age- and sex-specific quartiles) to internal carotid artery stenosis (>25%), and log-transformed common and internal carotid intima-media thickness (CC-IMT, IC-IMT, respectively).
Detectable MMP-9 was associated with carotid stenosis (OR 1.71, p=0.032) but not with IMT. Higher TIMP-1 was associated with carotid stenosis (OR for Q4 versus Q1-3, 1.63, p=0.022) and a higher IC-IMT (β 0.057 ±0.025, Q4 versus Q1-3, p=0.023). Higher PIIINP (Q4 versus Q1-3) showed a borderline association with carotid stenosis (OR 1.45 for Q4 versus Q1-3, p=0.095) but not with IMT. TIMP-1 was not associated with CC-IMT.
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 artery. Our findings are consistent with regional differences in matrix remodeling in the carotid artery.
Keywords: Carotid artery, atherosclerosis, matrix proteins, intima media thickness, stenosis