Hemostasis in middle-aged women with coronary heart disease
Author: Eriksson-Berg, Margita
Date: 2004-09-10
Location: Loben, plan 5 Thoraxkliniken, Karolinska Universitetssjukhuset
Time: 9.00
Department: Institutionen för medicin / Department of Medicine
Abstract
Inflammation and hemostasis play important roles in atherosclerotic disease. Chronic low-grade inflammation contributes to plaque vulnerability and rupture, and the subsequent thrombus formation is identified as the key mechanism in the pathogenesis of the acute coronary syndromes. Furthermore, hemostatic deterioration and the acute-phase reactant C-reactive protein have emerged as risk indicators for coronary heart disease (CHD). However, most data on the role of hemostatic factors in CHD is based on studies in men, and fewer studies have included women.
The Stockholm Female Coronary Risk Study, a community-based study, included women aged 65 years or younger who were hospitalized for an acute coronary event. A total of 292 patients and 292 controls were included in the study. The mean age±SD were 56±7 years in both patients and controls. Plasma levels of fibrinogen, coagulation factor VII (FVII), von Willebrand factor antigen (vWFag) and plasminogen activator inhibitor1 activity (PAI-1), and serum Creactive protein (CRP), were assessed as risk factors for cardiovascular disease and mortality. We also examined the influence of functional polymorphisms in the FVII gene on plasma levels of FVII, and gene environment interactions. In a substudy of 25 women with previous Q-wave myocardial infarction and 25 healthy controls, the coagulation and fibrinolytic responses to acute submaximal physical exercise were investigated.
In study I the mean plasma level of fibrinogen was higher in patients than in controls, and plasma fibrinogen levels were related to established cardiovascular risk factors in both groups. In the case-control analysis, the risk of being hospitalized for an acute coronary event was -3 times higher for women in the highest quartile of plasma fibrinogen compared with women in the lowest quartile, after control for several possible confounders.
In study II the mean plasma levels of FVII antigen (VIIag), but not of activated FVII (VIIa), were higher in patients than in controls, and VIIag and VIla levels were related to established cardiovascular risk factors in both groups. Serum triglyceride levels were the strongest predictor of VIIag. Neither VIIag plasma levels, although elevated, nor VIIa levels were independently associated with manifest CHD.
In study III the influence of functional polymorphisms in the FVII gene on plasma levels of FVII was stronger on factor Vila than on factor VIIag, whereas the relative contributions of cardiovascular risk factors were substantially higher for factor VIIag than for factor Vila. There were no FVII gene-environment interactions in women with or without CHD. Female homozygous carriers of the rare -670C allele (and of the rare -402A allele) were at higher risk of CHD than female homozygous carriers of the wild-type -670A (and -402G) allele.
In study IV the coagulation and fibrinolytic responses to acute submaximal physical exercise were assessed in 25 women with previous Q-wave MI and they had no signs of coagulation activation and retained fibrinolytic response in comparison with healthy controls.
In study V women with CHD were followed for 9 years and the baseline plasma level of fibrinogen was a predictor of all-cause mortality and acute cardiovascular events, plasma vWFag was predictive of all-cause mortality, and CRP was associated with acute cardiovascular events.
Conclusions: Plasma fibrinogen and vWFag levels were associated with longterm risk of CHD and mortality in middle-aged women, whereas VIIag, Vila and PAI-1 were not. In a study of polymorphisms in the FVII gene, the relative contributions of genotypes were stronger on factor VIIa than on factor VIIag levels. There were no factor VII gene-environment interactions. Furthermore, women with previous MI had no signs of coagulation activation and retained fibrinolytic response after acute submaximal physical exercise in comparison with healthy controls.
The Stockholm Female Coronary Risk Study, a community-based study, included women aged 65 years or younger who were hospitalized for an acute coronary event. A total of 292 patients and 292 controls were included in the study. The mean age±SD were 56±7 years in both patients and controls. Plasma levels of fibrinogen, coagulation factor VII (FVII), von Willebrand factor antigen (vWFag) and plasminogen activator inhibitor1 activity (PAI-1), and serum Creactive protein (CRP), were assessed as risk factors for cardiovascular disease and mortality. We also examined the influence of functional polymorphisms in the FVII gene on plasma levels of FVII, and gene environment interactions. In a substudy of 25 women with previous Q-wave myocardial infarction and 25 healthy controls, the coagulation and fibrinolytic responses to acute submaximal physical exercise were investigated.
In study I the mean plasma level of fibrinogen was higher in patients than in controls, and plasma fibrinogen levels were related to established cardiovascular risk factors in both groups. In the case-control analysis, the risk of being hospitalized for an acute coronary event was -3 times higher for women in the highest quartile of plasma fibrinogen compared with women in the lowest quartile, after control for several possible confounders.
In study II the mean plasma levels of FVII antigen (VIIag), but not of activated FVII (VIIa), were higher in patients than in controls, and VIIag and VIla levels were related to established cardiovascular risk factors in both groups. Serum triglyceride levels were the strongest predictor of VIIag. Neither VIIag plasma levels, although elevated, nor VIIa levels were independently associated with manifest CHD.
In study III the influence of functional polymorphisms in the FVII gene on plasma levels of FVII was stronger on factor Vila than on factor VIIag, whereas the relative contributions of cardiovascular risk factors were substantially higher for factor VIIag than for factor Vila. There were no FVII gene-environment interactions in women with or without CHD. Female homozygous carriers of the rare -670C allele (and of the rare -402A allele) were at higher risk of CHD than female homozygous carriers of the wild-type -670A (and -402G) allele.
In study IV the coagulation and fibrinolytic responses to acute submaximal physical exercise were assessed in 25 women with previous Q-wave MI and they had no signs of coagulation activation and retained fibrinolytic response in comparison with healthy controls.
In study V women with CHD were followed for 9 years and the baseline plasma level of fibrinogen was a predictor of all-cause mortality and acute cardiovascular events, plasma vWFag was predictive of all-cause mortality, and CRP was associated with acute cardiovascular events.
Conclusions: Plasma fibrinogen and vWFag levels were associated with longterm risk of CHD and mortality in middle-aged women, whereas VIIag, Vila and PAI-1 were not. In a study of polymorphisms in the FVII gene, the relative contributions of genotypes were stronger on factor VIIa than on factor VIIag levels. There were no factor VII gene-environment interactions. Furthermore, women with previous MI had no signs of coagulation activation and retained fibrinolytic response after acute submaximal physical exercise in comparison with healthy controls.
List of papers:
I. Eriksson M, Egberg N, Wamala S, Orth-Gomer K, Mittleman MA, Schenck-Gustafsson K (1999). Relationship between plasma fibrinogen and coronary heart disease in women. Arterioscler Thromb Vasc Biol. 19(1): 67-72.
Pubmed
II. Eriksson-Berg M, Silveira A, Orth-Gomer K, Hamsten A, Schenck-Gustafsson K (2001). Coagulation factor VII in middle-aged women with and without coronary heart disease. Thromb Haemost. 85(5): 787-92.
Pubmed
III. Eriksson-Berg M, Deguchi H, Hawe E, Scanavini D, Orth-Gomer K, Schenck-Gustafsson K, Humphries SE. Silveira A, Hamsten A (2004). Influence of factor VII gene polymorphisms and environmental factors on plasma coagulation factor VII concentrations in middleaged women with and without manifest coronary heart disease. [Manuscript]
IV. Eriksson-Berg M, Egberg N, Eksborg S, Schenck-Gustafsson K (2002). Retained fibrinolytic response and no coagulation activation after acute physical exercise in middle-aged women with previous myocardial infarction. Thromb Res. 105(6): 481-6.
Pubmed
V. Eriksson-Berg M, Janszky I, Orth-Gomer K, Schenck-Gustafsson K (2004). Relation of markers of inflammation and hemostasis to long-term mortlity and incident myocardial infarction in women with coronary heart disease. [Manuscript]
I. Eriksson M, Egberg N, Wamala S, Orth-Gomer K, Mittleman MA, Schenck-Gustafsson K (1999). Relationship between plasma fibrinogen and coronary heart disease in women. Arterioscler Thromb Vasc Biol. 19(1): 67-72.
Pubmed
II. Eriksson-Berg M, Silveira A, Orth-Gomer K, Hamsten A, Schenck-Gustafsson K (2001). Coagulation factor VII in middle-aged women with and without coronary heart disease. Thromb Haemost. 85(5): 787-92.
Pubmed
III. Eriksson-Berg M, Deguchi H, Hawe E, Scanavini D, Orth-Gomer K, Schenck-Gustafsson K, Humphries SE. Silveira A, Hamsten A (2004). Influence of factor VII gene polymorphisms and environmental factors on plasma coagulation factor VII concentrations in middleaged women with and without manifest coronary heart disease. [Manuscript]
IV. Eriksson-Berg M, Egberg N, Eksborg S, Schenck-Gustafsson K (2002). Retained fibrinolytic response and no coagulation activation after acute physical exercise in middle-aged women with previous myocardial infarction. Thromb Res. 105(6): 481-6.
Pubmed
V. Eriksson-Berg M, Janszky I, Orth-Gomer K, Schenck-Gustafsson K (2004). Relation of markers of inflammation and hemostasis to long-term mortlity and incident myocardial infarction in women with coronary heart disease. [Manuscript]
Issue date: 2004-08-20
Publication year: 2004
ISBN: 91-7349-978-1
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