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Associations of Hemostatic Variables with Cardiovascular Disease and Total Mortality: The Glasgow MONICA Study
Gordon D O Lowe1, Sanne A E Peters2,3,4, Ann Rumley1
1Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
Insights
Plasma levels of certain clotting factors, like factor VIII, are linked to higher mortality risk. Further research is needed to understand these hemostatic factors
Area of Science:
- Cardiovascular Medicine
- Hematology
- Epidemiology
Background:
- The relationship between plasma levels of hemostatic factors (excluding fibrinogen) and risks for cardiovascular disease (CVD) and overall mortality requires further clarification.
- Hemostasis involves complex interactions of coagulation factors, inhibitors, and fibrinolytic factors, all potentially influencing cardiovascular health.
Purpose of the Study:
- To investigate the associations between plasma levels of various hemostatic factors and the risks of developing CVD and all-cause mortality.
- To examine specific coagulation factors (VII, VIII, IX), inhibitors (antithrombin, protein C, protein S), activation markers (prothrombin fragment 1+2, thrombin-antithrombin complexes, D-dimer), and fibrinolytic factors (t-PA, PAI-1).
Main Methods:
- Utilized data from two phases of the Glasgow MONICA study, involving 382 to 1,123 participants (aged 30-74) without baseline CVD.
- Assayed plasma levels of multiple hemostatic factors and followed participants for 15 to 20 years to track CVD and mortality events.
- Calculated age- and sex-adjusted hazard ratios (HRs) for CVD and mortality, with further adjustments for established CVD risk factors.
Main Results:
- Initially, elevated levels of factor VIII and factor IX showed a significant association with CVD risk, but this attenuated after adjusting for other risk factors.
- In contrast, higher levels of factor VIII, D-dimer, and tissue plasminogen activator (t-PA) were strongly associated with all-cause mortality even after comprehensive risk factor adjustment.
- The study highlights distinct associations for different hemostatic factors concerning CVD risk versus overall mortality.
Conclusions:
- Factor VIII, D-dimer, and t-PA show a significant association with all-cause mortality, independent of traditional CVD risk factors.
- The predictive value of some coagulation factors for CVD risk appears to be mediated by other established risk factors.
- Further comprehensive studies, including meta-analyses, are essential to fully elucidate the roles of these hemostatic factors in the risks of specific cardiovascular events and mortality causes.
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.
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