Which hemostatic markers add to the predictive value of conventional risk factors for coronary heart disease and ischemic stroke? The Caerphilly Study.
BACKGROUND
Few studies have examined whether hemostatic markers contribute to risk of coronary disease and ischemic stroke independently of conventional risk factors. This study examines 11 hemostatic markers that reflect different aspects of the coagulation process to determine which have prognostic value after accounting for conventional risk factors.


RESULTS
A total of 2398 men aged 49 to 65 years were examined in 1984 to 1988, and the majority gave a fasting blood sample for assay of lipids and hemostatic markers. Men were followed up for a median of 13 years, and cardiovascular disease (CVD) events were recorded. There were 486 CVD events in total, 353 with prospective coronary disease and 133 with prospective ischemic stroke. On univariable analysis, fibrinogen, low activated protein C ratio, D-dimer, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) were associated significantly with risk of CVD. On multivariable analyses with conventional risk factors forced into the proportional hazards model, fibrinogen, D-dimer, and PAI-1 were significantly associated with risk of CVD, whereas factor VIIc showed an inverse association (P=0.001). In a model that contained the conventional risk factors, the hazard ratio for subsequent CVD in the top third of the distribution of predicted risk relative to the bottom third was 2.7 for subjects without preexisting CVD. This ratio increased to 3.7 for the model that also contained the 4 hemostatic factors.


CONCLUSIONS
Fibrinogen, D-dimer, PAI-1 activity, and factor VIIc each has potential to increase the prediction of coronary disease/ischemic stroke in middle-aged men, in addition to conventional risk factors.
Smith
Ann
A
Department of Epidemiology and Public Health, Queen's University, Belfast BT12 6BJ, UK.
Patterson
Chris
C
Yarnell
John
J
Rumley
Ann
A
Ben-Shlomo
Yoav
Y
Lowe
Gordon
G
D000368:Aged; D015415:Biomarkers / Q000097:blood*; D003327:Coronary Disease / Q000453:epidemiology*; D005169:Factor VIII / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis*; D006487:Hemostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011237:Predictive Value of Tests; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology*; D010959:Tissue Plasminogen Activator / Q000032:analysis; D006113:United Kingdom / Q000453:epidemiology; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D014841:von Willebrand Factor; D005169:Factor VIII; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator