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

Abstract

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.