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Update on fibrinogen as a cardiovascular risk factor
W B Kannel1, R B D'Agostino, A J Belanger
1Department of Medicine, Evans Memorial Research Foundation, School of Medicine, Framingham Heart Study, MA 01701.
Insights
High-normal fibrinogen levels are linked to increased risk of atherosclerotic cardiovascular disease. Lowering fibrinogen may protect high-risk individuals, suggesting it should be a major cardiovascular risk factor.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Epidemiology
Background:
- Mounting evidence suggests a causal link between elevated fibrinogen and atherosclerotic cardiovascular disease (ASCVD).
- Fibrinogen plays a thrombogenic role in atherosclerosis, influencing clinical manifestations.
- Identifying high-risk individuals and implementing protective strategies by managing fibrinogen levels is a key possibility.
Purpose of the Study:
- To examine the relationship between antecedent fibrinogen levels and the subsequent development of cardiovascular disease.
- To investigate associations with coronary heart disease, stroke, peripheral arterial disease, and cardiac failure.
- To analyze these relationships in a cohort of men and women aged 47-79 over 18 years.
Main Methods:
- Prospective surveillance of 1274 men and women from the Framingham Study over 18 years.
- Age-adjusted statistical analysis to determine relationships between fibrinogen levels and cardiovascular outcomes.
- Adjustment for coexistent risk factors including hypertension, diabetes, smoking, obesity, and hematocrit.
Main Results:
- Significant age-adjusted relationships were found between fibrinogen levels and coronary heart disease (CHD) and general cardiovascular disease (CVD) in both sexes.
- In women, significant associations were observed for cardiac failure and peripheral arterial disease (PAD), but not stroke.
- Each standard deviation increase in fibrinogen was associated with a 30% increase in CHD for men and 40% for women. Elevated fibrinogen independently contributes to CVD risk, especially in smokers, hypertensives, and diabetics.
Conclusions:
- Fibrinogen should be recognized as a major cardiovascular risk factor.
- Elevated fibrinogen levels within the "normal range" are associated with excess cardiovascular events.
- Further trials are needed to evaluate interventions aimed at lowering fibrinogen in high-risk individuals.
Abstract:
Mounting data support a causal connection between high-normal fibrinogen levels and atherosclerotic cardiovascular disease. There is clearly a thrombogenic component to atherosclerosis and the onset of clinical manifestations. This offers the possibility to better identify high-risk candidates and also to protect them by reducing blood fibrinogen concentration or blocking its action. The relationship of antecedent fibrinogen to the subsequent development of cardiovascular disease is examined, based on 18 years of surveillance of a cohort of 1274 men and women aged 47 to 79 years who participated in the Framingham Study. The association with the development of peripheral arterial disease and cardiac failure is now examined in addition to previously studied relationships to coronary heart disease and stroke. In men and women, there is a significant age-adjusted relationship of fibrinogen level to coronary heart disease and to cardiovascular disease in general. In women, a significant relationship to cardiac failure and peripheral arterial disease, but not to stroke, was also found. These data on women are unique as they are not available elsewhere. Age-adjusted cardiovascular, all-cause, and coronary heart disease mortality were all related to fibrinogen in both sexes. In men, fibrinogen impact was the greatest for stroke and the least for peripheral arterial disease. For women, the impact on coronary heart disease was greatest. The absolute risk for an elevated fibrinogen level was greatest for coronary heart disease in both sexes. Average fibrinogen values are higher in women and in persons with other risk factors, including hypertension, cigarette smoking, diabetes, obesity, and elevated hematocrit. However, there is an independent contribution of fibrinogen to cardiovascular disease in general and coronary disease in particular, on adjustment for coexistent risk factors. Fibrinogen enhances the risk of cardiovascular disease in hypertensives, diabetics, and cigarette smokers. About half the cardiovascular risk of cigarette smoking appears due to the higher fibrinogen values. Now, five prospective studies document the excess incidence of cardiovascular events in persons with elevated fibrinogen levels within the "normal range." Each standard deviation increase in fibrinogen is associated with a 30% increment of coronary heart disease in men and a 40% increase in women. Fibrinogen should be added to the list of major cardiovascular risk factors. Trials of intervention to lower fibrinogen in high-risk coronary candidates are needed.