Cross-sectional relations of multiple biomarkers representing distinct biological pathways to plasma markers of collagen metabolism in the community.
OBJECTIVE
Hyperhomocysteinemia, neurohormonal activation, inflammation and altered fibrinolysis have been linked to atherothrombosis as well as to myocardial fibrosis and heart failure. Hence, we related a panel of biomarkers representing these pathways to plasma markers of collagen metabolism in a large community-based sample.


METHODS
We related nine biomarkers representing select biologic pathways (independent variables: C-reactive protein, B-type natriuretic peptide, N-terminal proatrial natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen activator inhibitor-1 and homocysteine) to three plasma markers of collagen turnover [dependent variables, separate models for each: aminoterminal propeptide of type III collagen, tissue inhibitor of metalloproteinases-1 and matrix metalloproteinase-9 (present versus absent)] in 921 Framingham Heart study participants (mean age 57 years; 58% women). Participants were separated a priori into those with left ventricular end-diastolic dimensions and wall thickness below sex-specific median values (referent group) and either measure at least 90th sex-specific percentile ('remodeled' group). We used stepwise multivariable regression analysis adjusting for cardiovascular risk factors to relate the panel of systemic biomarkers to the three biomarkers of collagen metabolism.


RESULTS
Plasma homocysteine was positively related to all three markers of collagen metabolism in the remodeled group and to aminoterminal propeptide of type III collagen and tissue inhibitor of metalloproteinases-1 in the referent group. Plasminogen activator inhibitor-1 was positively related to aminoterminal propeptide of type III collagen and tissue inhibitor of metalloproteinases-1 in both groups, whereas the natriuretic peptides were associated positively with these collagen markers in the referent group.


CONCLUSIONS
In our large community-based sample, plasma homocysteine and plasminogen activator inhibitor-1 were positively related to circulating collagen biomarkers, consistent with experimental studies implicating these pathways in cardiovascular collagen turnover.
Cardiology Section (111), VA Boston Healthcare System, Boston, Massachusetts, USA. Jacob.joseph@bmc.org
Jacob
J
Joseph
Michael J
MJ
Pencina
Thomas J
TJ
Wang
Laura
L
Hayes
Geoffrey H
GH
Tofler
Paul
P
Jacques
Jacob
J
Selhub
Daniel
D
Levy
Ralph B
RB
D'Agostino
Emelia J
EJ
Benjamin
Ramachandran S
RS
Vasan
D000368:Aged; D000450:Aldosterone / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism; D003430:Cross-Sectional Studies; D003625:Data Collection; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011498:Protein Precursors / Q000097:blood; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D020257:Ventricular Remodeling / Q000502:physiology
D015415:Biomarkers; D024061:Collagen Type III; D005338:Fibrin Fibrinogen Degradation Products; C099254:N-terminal proatrial natriuretic peptide; D017395:Plasminogen Activator Inhibitor 1; D011498:Protein Precursors; D019715:Tissue Inhibitor of Metalloproteinase-1; C036309:fibrin fragment D; D006710:Homocysteine; D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D005340:Fibrinogen; D003094:Collagen; D002097:C-Reactive Protein; D012083:Renin; D020780:Matrix Metalloproteinase 9