Abstract
The associations of plasma levels of hemostatic factors, other than fibrinogen, with risks of cardiovascular disease (CVD) and all-cause mortality are not well defined. In two phases of the Glasgow MONICA study, we assayed coagulation factors (VII, VIII, IX, and von Willebrand factor), coagulation inhibitors (antithrombin, protein C, protein S), coagulation activation markers (prothrombin fragment 1 + 2, thrombin–antithrombin complexes, D-dimer), and the fibrinolytic factors, tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor type 1. Over 15 to 20 years, we followed up between 382 and 1,123 men and women aged 30 to 74 years, without baseline CVD, for risks of CVD and mortality. Age- and sex-adjusted hazard ratios (HRs) for CVD (top third vs bottom third) were significant only for factor VIII (1.30; 95% confidence interval [CI], 1.06–1.58) and factor IX (1.18; 95% CI, 1.01–1.39); these HRs were attenuated by further adjustment for CVD risk factors: 1.17 (95% CI, 0.94–1.46) and 1.07 (95% CI, 0.92–1.25), respectively. In contrast, factor VIII (HR, 1.63; 95% CI, 1.35–1.96), D-dimer (HR, 2.34; 95% CI, 1.26–4.35), and t-PA (HR, 2.81; 95% CI, 1.43–5.54) were strongly associated with mortality after full risk factor adjustment. Further studies, including meta-analyses, are required to assess the associations of these hemostatic factors with the risks of stroke and heart disease and causes of mortality.
Highlights
From the prospective Glasgow MONICA (Monitoring of Trends and Determinants of Cardiovascular Disease) study, we report the associations with incident cardiovascular disease (CVD) (CHD and stroke), and with total mortality, of plasma levels of coagulation factors VII, VIII, and IX; coagulation activation markers prothrombin fragment 1 þ 2 (F1 þ 2), thrombin–antithrombin (TAT) complexes, and D-dimer; coagulation inhibitors antithrombin and protein C and protein S; activated partial thromboplastin time, activated protein C (APC) resistance, and its common genetic determinant; and the fibrinolytic variables tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor type 1 (PAI-1) activity
We found no compelling evidence of independent associations of hemostatic variables with CVD, suggesting that they may not add significantly to CVD risk stratification
We report that factor VIII, D-dimer, and t-PA were strongly associated with total mortality after full risk factor adjustment, but found no such association for other hemostatic variables
Summary
Plasma levels of some hemostatic factors and activation markers have been associated with the risk of arterial cardiovascular diseases (CVDs): coronary heart disease (CHD), stroke, and peripheral arterial disease (PAD).[1,2]. From the prospective Glasgow MONICA (Monitoring of Trends and Determinants of Cardiovascular Disease) study, we report the associations with incident CVD (CHD and stroke), and with total mortality, of plasma levels of coagulation factors VII, VIII, and IX; coagulation activation markers prothrombin fragment 1 þ 2 (F1 þ 2), thrombin–antithrombin (TAT) complexes, and D-dimer; coagulation inhibitors antithrombin and protein C and protein S; activated partial thromboplastin time (aPTT), activated protein C (APC) resistance, and its common genetic determinant (the FV:R506Q mutation); and the fibrinolytic variables t-PA antigen and plasminogen activator inhibitor type 1 (PAI-1) activity
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