Association of hemostatic variables with prevalent cardiovascular disease and asymptomatic carotid artery atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study Investigators.

Folsom, Aaron R.; Wu, Kenneth K.; Shahar, Eyal; Davis, C. E.

doi:10.1161/01.atv.13.12.1829

Cited by 156 publications

(79 citation statements)

References 34 publications

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“…We also examined a cross-genetic influence of VWF SNPs that we have recently studied 26 on FVIII activity. Consistent with a previous report, 27 FVIII activity varied significantly among subjects ( Figure 1) and was higher in AA subjects than EA subjects, but the FVIII-VWF ratio was comparable between the 2 ethnic groups (Table 1). This difference may be in part attributed to a higher BMI and increased prevalence of diabetes and hypertension in AA subjects (supplemental Figure 2A) because these covariates are known to associate with inflammation, a condition that increases secretion of acute-phase reactants such as FVIII and VWF.…”

Section: Discussionsupporting

confidence: 91%

“…FVIII activity was measured by the ability of a testing sample to correct clotting time of human FVIII-deficient plasma and reported as a percentage (George King Biomedical Inc). 27 VWF Ag was determined by a commercial ELISA kit (American Bioproducts) and reported as a percentage of the Universal Coagulation Reference Plasma (Thromboscreen, Pacific Hemostasis; Curtin Matheson Scientific Inc). The reliability coefficient (1 Ϫ intraindividual variance/total variance) obtained from repeat testing of individuals over several weeks was 0.68 for VWF and 0.86 for FVIII.…”

Section: Baseline Measurementsmentioning

confidence: 99%

“…Age, race, sex, body mass index (BMI), hypertension, diabetes, ever smoking status, and ABO genotype were adjusted for their known impacts on VWF and FVIII. 27,28 …”

Section: Baseline Measurementsmentioning

confidence: 99%

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Influence of single nucleotide polymorphisms in factor VIII and von Willebrand factor genes on plasma factor VIII activity: the ARIC Study

Campos

Buchanan

Barbalić

et al. 2012

Blood

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Factor VIII (FVIII) functions as a cofactor for factor IXa in the contact coagulation pathway and circulates in a protective complex with von Willebrand factor (VWF). Plasma FVIII activity is strongly influenced by environmental and genetic factors through VWF-dependent and -independent mechanisms. Single nucleotide polymorphisms (SNPs) of the coding and promoter sequence in the FVIII gene have been extensively studied for effects on FVIII synthesis, secretion, and activity, but impacts of non–disease-causing intronic SNPs remain largely unknown. We analyzed FVIII SNPs and FVIII activity in 10 434 healthy Americans of European (EA) or African (AA) descent in the Atherosclerosis Risk in Communities (ARIC) study. Among covariates, age, race, diabetes, and ABO contributed 2.2%, 3.5%, 4%, and 10.7% to FVIII intersubject variation, respectively. Four intronic FVIII SNPs associated with FVIII activity and 8 with FVIII-VWF ratio in a sex- and race-dependent manner. The FVIII haplotypes AT and GCTTTT also associated with FVIII activity. Seven VWF SNPs were associated with FVIII activity in EA subjects, but no FVIII SNPs were associated with VWF Ag. These data demonstrate that intronic SNPs could directly or indirectly influence intersubject variation of FVIII activity. Further investigation may reveal novel mechanisms of regulating FVIII expression and activity.

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Section: Discussionsupporting

confidence: 91%

Section: Baseline Measurementsmentioning

confidence: 99%

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Influence of single nucleotide polymorphisms in factor VIII and von Willebrand factor genes on plasma factor VIII activity: the ARIC Study

Campos

Buchanan

Barbalić

et al. 2012

Blood

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“…However, the plasma concentrations of the hemostatic factors presented herein are consistent with previous studies involving both sedentary 7,47,48 and physically active 10 populations. In addition, the favorable plasma levels of fibrinogen, t-PA antigen, t-PA activity, and PAI-1 activity associated with regular physical activity in the present study are similar to those reported in response to endurance exercise training in older men.…”

Section: Limitationssupporting

confidence: 90%

Physical Activity Status and Adverse Age-Related Differences in Coagulation and Fibrinolytic Factors in Women

DeSouza

Jones

Seals

1998

ATVB

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Abstract-Adverse changes in coagulation and fibrinolytic factors are thought to contribute to the increased risk of cardiovascular disease and atherothrombosis with age. We tested the hypothesis that such age-related changes in specific coagulation and fibrinolytic factors are absent in physically active women. Resting levels of plasma fibrinogen, tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor-1 (PAI-1) antigen and activity, and fibrin D-dimer were measured in 24 healthy premenopausal women: 11 sedentary (aged 28Ϯ1 years; Pre-S) and 13 physically active (aged 30Ϯ1 years; Pre-PA) and in 27 healthy postmenopausal women: 14 sedentary (aged 61Ϯ1 years; Post-S) and 13 physically active (aged 58Ϯ1 years; Post-PA). Post-S had higher (PϽ.05) fibrinogen, t-PA antigen, PAI-1 antigen, PAI-1 activity, and fibrin D-dimer levels and lower t-PA activity than Pre-S. Post-PA demonstrated lower (PϽ.01) plasma fibrinogen, t-PA antigen, PAI-1 antigen, and PAI-1 activity and higher (PϽ.01) t-PA activity levels than Post-S. In addition, plasma fibrin D-dimer levels tended (Pϭ.06) to be lower in Post-PA than in Post-S. Although plasma levels of fibrinogen and fibrin D-dimer in Post-PA were lower than in Post-S, they were higher (PϽ.05) than in Pre-PA. Importantly, however, the fibrinolytic profile of Post-PA did not differ from that of Pre-PA. The results of the present study demonstrate that the adverse age-associated differences in plasma fibrinogen concentrations and the endogenous fibrinolytic system in sedentary healthy women are either attenuated or absent in highly physically active women. The smaller or absent age-related differences in coagulation and fibrinolytic factors in women who habitually exercise may represent an important mechanism contributing to their lower age-related increase in both cardiovascular disease and atherothrombotic events. Future studies need to determine whether women who are moderately active would demonstrate the same favorable hemostatic profile. (Arterioscler Thromb Vasc Biol. 1998;18:362-368.)Key Words: aging Ⅲ exercise Ⅲ fibrinogen Ⅲ fibrinolytic system Ⅲ fibrin D-dimer A dvancing age is associated with an increased risk of CVD in general and atherosclerotic vascular disease in particular. 1 In women, the incidence of both CVD and thrombosis increases after the onset of menopause. 2,3 It has been suggested that age-related changes in coagulation and fibrinolytic factors contribute to the increased risk of atherothrombotic events in postmenopausal women by accelerating the atherosclerotic process and promoting thrombus formation. 4 -6 Indeed, higher plasma concentrations of fibrinogen 4 and fibrin D-dimer, 7 both markers of thrombogenic risk, and reduced endogenous fibrinolytic activity 5 have been reported in healthy postmenopausal compared with premenopausal women.In contrast to aging, regular physical activity is associated with favorable coagulation and fibrinolytic function. 8 -10 We have previously shown that physically active postmenopausal...

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“…These factors also may play a pathophysiological role in stroke by enhancing atherosclerosis or thrombosis of the carotid or cerebral arteries, by reducing blood flow in the cerebral microvasculature, or by enhancing tissue injury from ischemic infarction. In the ARIC Study, fibrinogen was cross-sectionally associated with carotid intima-media thickness, but von Willebrand factor, factor VIIIc, and protein C were not 31 ; this suggests that increased carotid atherosclerosis is not an important mechanism by which these factors increase risk of stroke.…”

Section: Folsom Et Al Hemostatic Factors and Ischemic Strokementioning

confidence: 96%

Prospective Study of Markers of Hemostatic Function With Risk of Ischemic Stroke

Rosamond²,

et al. 1999

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for the Atherosclerosis Risk in Communities (ARIC) Study InvestigatorsBackground-Several markers of hemostatic function and inflammation have been associated with increased risk of coronary heart disease, but prospective evidence for their role in ischemic stroke is scant. Methods and Results-The Atherosclerosis Risk in Communities (ARIC) Study measured several of these markers in more than 14 700 participants 45 to 64 years old who were free of cardiovascular disease and were followed up for 6 to 9 years for occurrence of ischemic stroke (nϭ191). There was no apparent association between ischemic stroke incidence and factor VIIc, antithrombin III, platelet count, or activated partial thromboplastin time. After adjustment for multiple cardiovascular risk factors, von Willebrand factor, factor VIIIc, fibrinogen, and white blood cell count were positively associated and protein C was negatively but nonsignificantly associated with ischemic stroke incidence in regression analyses based on either continuous variables or fourths of the variable distributions. The adjusted relative risk (and 95% CI) for ischemic stroke in those in the highest versus lowest fourth were: von Willebrand factor, 1.71 (1.1 to 2.7); factor VIIIc, 1.93 (1.2 to 3.1); white blood cell count, 1.50 (0.9 to 2.4); fibrinogen, 1.26 (0.8 to 2.0); and protein C, 0.65 (0.4 to 1.0). Conclusions-This study offers modest support for the hypothesis that some markers of hemostatic function and inflammation can identify groups of middle-aged adults at increased risk of stroke. These factors may play a role in the pathogenesis of ischemic stroke. (Circulation. 1999;100:736-742.)

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Association of hemostatic variables with prevalent cardiovascular disease and asymptomatic carotid artery atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study Investigators.

Cited by 156 publications

References 34 publications

Influence of single nucleotide polymorphisms in factor VIII and von Willebrand factor genes on plasma factor VIII activity: the ARIC Study

Influence of single nucleotide polymorphisms in factor VIII and von Willebrand factor genes on plasma factor VIII activity: the ARIC Study

Physical Activity Status and Adverse Age-Related Differences in Coagulation and Fibrinolytic Factors in Women

Prospective Study of Markers of Hemostatic Function With Risk of Ischemic Stroke

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