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Factor VIII, ABO blood group and the incidence of ischaemic heart disease
T W Meade1, J A Cooper, Y Stirling
1MRC Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, Medical College of St Bartholomew's Hospital, London.
Insights
High levels of factor VIII activity and von Willebrand factor antigen are linked to increased risk of fatal ischemic heart disease (IHD). Blood group AB independently increases IHD risk, possibly due to genetic factors influencing other risk indicators.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Epidemiology
Background:
- Ischemic heart disease (IHD) is a leading cause of mortality.
- The role of hemostatic factors, such as factor VIII and von Willebrand factor, in IHD pathogenesis requires further elucidation.
- ABO blood group has been inconsistently associated with cardiovascular risk.
Purpose of the Study:
- To investigate the association between factor VIII activity (FVIIIC), von Willebrand factor antigen (vWFAg), and IHD incidence.
- To examine the independent and combined effects of these hemostatic factors and ABO blood groups on IHD risk.
- To explore potential genetic markers influencing IHD risk.
Main Methods:
- Prospective cohort study (Northwick Park Heart Study) of 1393 men aged 40-64.
- Follow-up for an average of 16.1 years, recording 178 first major IHD episodes.
- Statistical analysis adjusting for ABO blood groups and accounting for measurement variability.
Main Results:
- Increased FVIIIC was associated with higher IHD incidence, particularly fatal events (28% increased risk per SD increase).
- vWFAg was also significantly associated with fatal IHD events.
- Blood group AB showed significantly higher IHD incidence, especially fatal events, independent of FVIIIC and vWFAg levels.
- High factor VIII levels may increase thrombotic potential, contributing to IHD.
- Blood group AB was associated with shorter stature, suggesting a potential genetic marker for IHD risk.
Conclusions:
- FVIIIC and vWFAg are significant risk factors for IHD, especially fatal outcomes.
- ABO blood group, particularly AB, is an independent risk factor for IHD.
- High factor VIII levels may promote IHD through increased thrombogenicity.
- Blood group AB might serve as a genetic marker for other IHD risk factors.
Abstract:
Relations of factor VIII activity, FVIIIC, and von Willebrand factor antigen (vWFAg), with ischaemic heart disease (IHD) were examined in 1393 men aged between 40 and 64 years at entry to the Northwick Park Heart Study (NPHS) who experienced 178 first major episodes of IHD during an average follow-up period of 16.1 years. After allowing for the large factor VIII differences between the main ABO blood groups, FVIIIC was probably associated with IHD incidence, possibly more strongly with fatal than non-fatal episodes. Thus, an increase of 1 standard deviation in FVIIIC raised the risk of fatal IHD by about 28%. vWFAg was also significantly associated with fatal events. The observed relation of FVIIIC with IHD incidence probably underestimates the true strength of the association because of the considerable within-person and laboratory variability in factor VIII measurements. FVIIIC and vWFAg were strongly correlated (r = 0.57) and in statistical terms there may be little to choose between them in long-term studies of IHD. Taking account of evidence that haemophiliacs seem to experience less IHD than expected, high factor VIII levels may contribute to the incidence of IHD by increasing thrombogenic potential. The incidence of IHD was significantly higher in those of blood group AB than in those of groups O, A or B, particularly for fatal events. There was no evidence that the FVIIIC and vWFAg associations with IHD are determined by ABO group. The factor VIII and ABO blood group effects therefore appeared to be independent. Group AB may be a genetic marker of characteristics influencing other indices of IHD risk such as short stature, NPHS men (though not women) of group AB being about 2 cm shorter than those of other groups.