Associations of factor VIIIc, D-dimer, and plasmin-antiplasmin with incident cardiovascular disease and all-cause mortality

Am J Hematol. 2009 Jun;84(6):349-53. doi: 10.1002/ajh.21429.


To examine the associations of three understudied hemostatic factors--D-dimer, factor VIII(c), and plasmin-antiplasmin (PAP) complex--with incident cardiovascular disease (CVD) and all cause mortality in the Multiethnic Study of Atherosclerosis cohort. Hemostatic factors were measured at baseline in 45-84-year-old patients (n = 6,391) who were free of clinically recognized CVD. Over 4.6 years of follow-up, we identified 307 CVD events, 207 hard coronary heart disease events, and 210 deaths. D-dimer, factor VIII(c), and PAP were not associated with CVD incidence after adjustment for other risk factors. In contrast, each factor was associated positively with total mortality, and D-dimer and factor VIII(c) were associated positively with cancer mortality. When modeled as ordinal variables and adjusted for risk factors, total mortality was greater by 33% (95% CI 15-54) for each quartile increment of D-dimer, 26% (11-44) for factor VIIIc, and 20% (4-38) for PAP. This prospective cohort study did not find D-dimer, factor VIII(c), or PAP to be risk factors for CVD. Instead, elevated levels of these three hemostatic factors were associated independently with increased risk of death. Elevated D-dimer and factor VIII(c) were associated with increased cancer death.

Publication types

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

MeSH terms

  • Age Factors
  • Aged
  • Calcium / metabolism
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / pathology
  • Carotid Arteries / metabolism
  • Carotid Arteries / pathology
  • Cohort Studies
  • Factor VIII / metabolism*
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Tunica Media / pathology
  • alpha-2-Antiplasmin / metabolism*


  • Fibrin Fibrinogen Degradation Products
  • alpha-2-Antiplasmin
  • fibrin fragment D
  • Factor VIII
  • Calcium