Relationship between markers of activated coagulation, their correlation with inflammation, and association with coronary heart disease (NPHSII)

J Thromb Haemost. 2008 Feb;6(2):259-67. doi: 10.1111/j.1538-7836.2008.02819.x. Epub 2007 Oct 29.


Objective: To determine whether activation of coagulation increases in parallel with inflammation and whether coagulation activation markers (CAMs) are independently associated with coronary heart disease (CHD), in the prospective study, NPHSII.

Methods: Surveillance of 2997 men between 50 and 63 years yielded 314 first CHD events during 36507 person-years of observation. The plasma levels of activated factor XII (FXIIa), the peptides released upon activation of factor X (FXpep) and factor IX (FIXpep), activated factor VII (FVIIa), prothrombin fragment 1 + 2 (F1 + 2) and fibrinopeptide A (FpA) served as indices of activity along the coagulation pathway. C reactive protein (CRP) provided a marker of inflammatory activity.

Results: While borderline or significant correlations were identified for each CAM with inflammation, as determined by CRP levels, these did not reach as high a numerical value as was shown for fibrinogen with CRP. FVIIa and FIXpep possessed independent associations with CHD: a one SD increase in adjusted FIXpep and FVIIa level was associated with a relative hazard of 1.20 (95% CI 1.00-1.43) and 0.70 (CI 0.58-0.86), respectively, using a group including all CHD events, compared with 'no-event'.

Conclusions: Inflammation has significant but minimal impact upon CAMs of the extrinsic coagulation pathway. Reduced FVIIa and increased FIXpep levels were found to be significant, independent, predictors of CHD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Blood Coagulation / physiology*
  • Blood Coagulation Factors / analysis*
  • C-Reactive Protein / analysis
  • Cohort Studies
  • Comorbidity
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / epidemiology
  • Coronary Disease / blood
  • Coronary Disease / epidemiology*
  • Dietary Fats / pharmacology
  • Disease Susceptibility
  • Enzyme Activation / drug effects
  • Factor IX / analysis
  • Factor VIIa / analysis
  • Hemophilia B / epidemiology
  • Humans
  • Inflammation / blood*
  • Inflammation / epidemiology
  • London / epidemiology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Risk Factors


  • Biomarkers
  • Blood Coagulation Factors
  • Dietary Fats
  • Factor IX
  • C-Reactive Protein
  • Factor VIIa