Relations of biomarkers of extracellular matrix remodeling to incident cardiovascular events and mortality.
OBJECTIVE
To evaluate if biomarkers reflecting left ventricular/vascular extracellular matrix remodeling are associated with cardiovascular disease (CVD) and death in the community.


RESULTS
In 922 Framingham Study participants (mean age, 58 years; 56% women), we related circulating concentrations of matrix metalloproteinase-9 (binary variable: detectable versus undetectable), log of tissue inhibitor of matrix metalloproteinase-1, and log of procollagen type III aminoterminal peptide (PIIINP) to incident CVD and death. On follow-up (mean, 9.9 years), 51 deaths and 81 CVD events occurred. Each SD increment of log of tissue inhibitor of matrix metalloproteinase-1 and log-PIIINP was associated with multivariable-adjusted hazards ratios of 1.72 (95% CI, 1.30 to 2.27) and 1.47 (95% CI, 1.11 to 1.96), respectively, for mortality risk. Log-PIIINP concentrations were also associated with CVD risk (hazard ratio [95% CI] per SD, 1.35 [1.05 to 1.74]). Death and CVD incidence rates were 2-fold higher in participants with both biomarkers higher than the median (corresponding hazard ratio [95% CI], 2.78 [1.43 to 5.40] and 1.77 [1.04 to 3.03], respectively) compared with those with either or both less than the median. The inclusion of both biomarkers improved the C-statistic (for predicting mortality) from 0.78 to 0.82 (P=0.03). Matrix metalloproteinase-9 was unrelated to either outcome.


CONCLUSIONS
Higher circulating tissue inhibitor of matrix metalloproteinase-1 and PIIINP concentrations are associated with mortality, and higher PIIINP is associated with incident CVD, in the community.
Velagaleti
Raghava S
RS
Framingham Heart Study, 73 Mount Wayte Ave, Framingham, MA 01702-58, USA.
Gona
Philimon
P
Sundström
Johan
J
Larson
Martin G
MG
Siwik
Deborah
D
Colucci
Wilson S
WS
Benjamin
Emelia J
EJ
Vasan
Ramachandran S
RS
D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology* / Q000401:mortality; D005109:Extracellular Matrix / Q000502:physiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D008955:Models, Cardiovascular; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011347:Procollagen / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D020257:Ventricular Remodeling / Q000502:physiology*
D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; D019715:Tissue Inhibitor of Metalloproteinase-1; C041876:procollagen Type III-N-terminal peptide; D020780:Matrix Metalloproteinase 9
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