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Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study
Insights
High levels of factor VII and fibrinogen, key clotting factors, significantly increase ischemic heart disease (IHD) risk, independent of cholesterol. These factors are crucial in IHD development, particularly in younger men and smokers.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Epidemiology
Background:
- Ischemic heart disease (IHD) is a leading cause of mortality.
- The role of thrombotic factors in IHD pathogenesis requires further investigation.
- Previous studies have primarily focused on cholesterol as a risk factor.
Purpose of the Study:
- To investigate the association between hemostatic function measures and IHD risk.
- To compare the predictive power of clotting factors versus cholesterol for IHD events.
- To explore potential mediators of the smoking-IHD relationship.
Main Methods:
- Prospective cohort study (Northwick Park Heart Study - NPHS).
- Inclusion of 1511 white men aged 40-64 at recruitment.
- Measurement of factor VII coagulant activity, plasma fibrinogen, and cholesterol levels.
Main Results:
- Elevated factor VII activity and plasma fibrinogen were independently associated with increased IHD risk.
- These associations were stronger than that for cholesterol, particularly for events within 5 years.
- High fibrinogen levels posed a greater IHD risk in younger men; smoking-IHD link may be fibrinogen-mediated.
Conclusions:
- The coagulation system, specifically factor VII and fibrinogen, plays a significant role in IHD development.
- Biochemical disturbances in coagulation may be as important as cholesterol metabolism in IHD.
- Hemostatic function should be considered in IHD risk assessment and prevention strategies.
Abstract:
The Northwick Park Heart Study (NPHS) has investigated the thrombotic component of ischaemic heart disease (IHD) by the inclusion of measures of haemostatic function. Among 1511 white men aged between 40 and 64 at the time of recruitment, 109 subsequently experienced first major events of IHD. High levels of factor VII coagulant activity and of plasma fibrinogen were associated with increased risk, especially for events occurring within 5 years of recruitment. These associations seemed to be stronger than for cholesterol, elevations of one standard deviation in factor VII activity, fibrinogen, and cholesterol being associated with increases in the risk of an episode of IHD within 5 years of 62%, 84%, and 43% respectively. Multiple regression analyses indicated independent associations between each of the clotting factor measures and IHD but not between the blood cholesterol level and IHD incidence. The risk of IHD in those with high fibrinogen levels was greater in younger than in older men. Much of the association between smoking and IHD may be mediated through the plasma fibrinogen level. The biochemical disturbance leading to IHD may lie at least as much in the coagulation system as in the metabolism of cholesterol.