Journal of Stroke and Cerebrovascular Diseases
Original ArticleAssociation of Carotid Artery Atherosclerosis With Circulating Biomarkers of Extracellular Matrix Remodeling: The Framingham Offspring Study
Section snippets
Study Cohort
The Framingham offspring cohort was recruited in 1971, and includes individuals who are either children or the spouses of the children of the participants in the original Framingham Heart Study. The members of the offspring cohort have been examined approximately every 4 to 8 years since 1971. At the sixth examination cycle, 3377 attendees underwent carotid duplex ultrasound. Participants with available carotid ultrasound measurements and plasma biomarkers of ECM turnover (MMP-9, TIMP-1, and/or
Results
Clinical characteristics for the study participants are shown in Table 1. Carotid artery stenosis greater than 25% was observed in 168 participants (17%).
MMP-9 was detectable in 680 participants (20%). The median plasma concentration was 31 ng/dL in men and 34 ng/mL in women (range 20-248 ng/mL).
Principal Findings
This study demonstrates site-specific relations of circulating biomarkers of ECM remodeling and the carotid artery atherosclerosis measures assessed using duplex ultrasound. First, we noted significant associations of higher levels of TIMP-1 with IC IMT, but not with CC IMT. The associations with IC IMT remained statistically significant after adjustment for traditional vascular risk factors. Second, higher concentrations of TIMP-1 and detectable MMP-9 were associated with IC stenosis, with a
Conclusions
Higher circulating concentrations of ECM turnover markers, TIMP-1, MMP-9, and PIIINP are associated with measures of carotid artery atherosclerosis after adjusting for standard risk factors in a community-based sample of middle-aged adults, free of clinical stroke and dementia. Our findings are consistent with site-specific carotid artery ECM remodeling and support a pathophysiologic role for the MMP/TIMP pathway in atherosclerosis of the carotid artery.
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Supported by the National Heart, Lung, and Blood Institute (NHBLI) Framingham Heart Study (National Institutes of Health/NHLBI Contract #N01-HC-25195); grants from the National Institute of Neurological Disorders and Stroke NS17950 (Dr. Wolf); the National Institute of Aging AG08122, AG16495 (Dr. Wolf); and NHBLI HL67288 and 2K24HL04334 (Dr Vasan).