Cross-sectional relations of multiple biomarkers representing distinct biological pathways to plasma markers of collagen metabolism in the community

J Hypertens. 2009 Jun;27(6):1317-24. doi: 10.1097/HJH.0b013e328329fc20.

Abstract

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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aldosterone / blood
  • Atrial Natriuretic Factor / blood
  • Biomarkers / blood*
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / metabolism
  • Collagen / metabolism*
  • Collagen Type III / metabolism
  • Cross-Sectional Studies
  • Data Collection
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Fibrinogen / metabolism
  • Fibrinolysis
  • Homocysteine / blood
  • Humans
  • Inflammation / blood
  • Inflammation / metabolism
  • Male
  • Matrix Metalloproteinase 9 / blood
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Plasminogen Activator Inhibitor 1 / blood
  • Protein Precursors / blood
  • Renin / blood
  • Renin-Angiotensin System / physiology
  • Tissue Inhibitor of Metalloproteinase-1 / blood
  • Ventricular Remodeling / physiology

Substances

  • Biomarkers
  • Collagen Type III
  • Fibrin Fibrinogen Degradation Products
  • N-terminal proatrial natriuretic peptide
  • Plasminogen Activator Inhibitor 1
  • Protein Precursors
  • Tissue Inhibitor of Metalloproteinase-1
  • fibrin fragment D
  • Homocysteine
  • Natriuretic Peptide, Brain
  • Aldosterone
  • Atrial Natriuretic Factor
  • Fibrinogen
  • Collagen
  • C-Reactive Protein
  • Renin
  • Matrix Metalloproteinase 9

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