Increased levels of endothelial haemostatic markers in patients with coronary heart disease

Schumacher, A.; Seljeflot, Ingebjørg; Sommervoll, L.; Christensen, Benedicte; Otterstad, Jan Erik; Arnesen, Harald

doi:10.1016/s0049-3848(01)00399-1

Cited by 23 publications

(18 citation statements)

References 33 publications

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“…The association between vWF and cardiovascular risk factors has been well documented in the literature. The results of Schumacher et al [37]indicate that vWF, but not TM, was an independent marker of atherosclerosis in patients with coronary heart disease. Blann et al [38]demonstrated that, of the endothelial injury markers, vWF correlates most closely with the Framingham risk factor prediction scores and may be a better plasma endothelial marker for the future development of an atherothrombotic event in healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress – a Link between Endothelial Injury, Coagulation Activation, and Atherosclerosis in Haemodialysis Patients

Pawlak¹,

Naumnik²,

Brzósko³

et al. 2004

Am J Nephrol

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Background/Aim: Recently emerging evidence suggests that oxidative stress (SOX) may participate in atherogenesis. The aim of the present study was to establish whether enhanced SOX, involving endothelial injury, activation of coagulation, and inflammatory reaction, could be implicated in atherosclerotic diseases in haemodialysis (HD) patients. Methods: Markers of SOX, endothelial injury, coagulation, and cytokines, were measured in the plasma of HD patients with and without cardiovascular disease (CVD), and of healthy controls by ELISA methods. Remodeling of the carotid arteries was assessed by measuring the intima-media thickness (IMT) as a surrogate of atherosclerotic disease in all groups. Results: Markers of SOX, endothelial injury, and extrinsic coagulation pathway activation and IMT values were significantly elevated in HD patients, especially in those with CVD when compared with the control group. The von Willebrand factor antigen (vWF:Ag) levels were more increased in the patients with CVD than in those without. Furthermore, the plasma levels of tumour necrosis factor alpha, monocyte chemo-attractant protein 1, and macrophage inflammatory protein 1 beta were significantly higher only in the HD group with CVD when compared with the controls. The IMT was strongly and directly correlated with Cu/Zn superoxide dismutase. Both IMT and Cu/Zn superoxide dismutase were positively correlated with age, thrombomodulin, vWF:Ag, tissue factor, tissue factor pathway inhibitor, prothrombin fragment F1 + 2, monocte chemo-attractant protein 1, macrophage inflammatory protein 1 beta, and tumour necrosis factor alpha levels. Multivariate analysis identified vWF:Ag as the only independent variable significantly associated with an increased IMT. Conclusions: The present study suggests that enhanced SOX, involved pro-atherogenic cytokine and chemokines levels, endothelial injury, and coagulation activation may constitute a pathway for accelerated atherosclerosis in HD patients. The significant, independent association between IMT and vWF:Ag should be assessed in future studies to determine whether vWF:Ag elevation is causative or a by-product of the increased IMT.

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Section: Discussionmentioning

confidence: 99%

Oxidative Stress – a Link between Endothelial Injury, Coagulation Activation, and Atherosclerosis in Haemodialysis Patients

Pawlak¹,

Naumnik²,

Brzósko³

et al. 2004

Am J Nephrol

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“…Von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) are molecules with haemostatic impact, which seem to play a role as indicators of cardiovascular disease and to predict increased risk of acute events [12][13][14][15][16][17][18][19]. The increased cardiovascular risk in dyslipidemic patients could be associated with prothrombotic state and impaired fibrinolytic activity.…”

Section: Introductionmentioning

confidence: 99%

Prothrombotic markers in asymptomatic dyslipidemic subjects

Karásek

Vaverková

Halenka

et al. 2010

J Thromb Thrombolysis

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The aim of this study was to evaluate the plasma levels of prothrombotic markers--von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA)--in asymptomatic subjects with dyslipidemia. Asymptomatic subjects with dyslipidemia and their relatives (n = 234) were assessed for lipids and prothrombotic markers. Individuals were divided into four dyslipidemic phenotypes (DLP) according to apolipoprotein B (apoB) and triglycerides (TG): DLP1 (n = 58, apoB < 1.2 g/l and TG < 1.5 mmol/l), DLP2 (n = 47, apoB < 1.2 g/l and TG ≥ 1.5 mmol/l), DLP3 (n = 31, apoB ≥ 1.2 g/l and TG < 1.5 mmol/l) and DLP4 (n = 98, apoB ≥ 1.2 g/l and TG ≥ 1.5 mmol/l). Associations between prothrombotic markers and risk factors for atherosclerosis, markers of insulin resistance, and the intima-media thickness of the common carotid artery (IMT) were assessed too. Significant differences in PAI-1 between normolipidemic phenotype--DLP1 (62.5 (35.9-82.9) ng/ml) and hypertriglyceridemic phenotypes--DLP2 (82.2 (61.1-122.1) ng/ml, p < 0.01) and DLP4 (91.4 (63.5-111.8) ng/ml, p < 0.001) after adjustment for age, sex and body mass index, were found. Levels of t-PA were different only between DLP1 and DLP4 (1.9 (0.9-3.3) ng/ml vs. 5.3 (2.5-8.6) ng/ml, p < 0.05). There were no significant differences of vWF between DLPs. PAI-1 and t-PA correlated with lipid parameters, markers of insulin resistance, blood pressure and obesity. VWF was independently associated with IMT, which was increased in DLP4. Individuals with hypertriglyceridemic phenotypes showed increased levels of PAI-1 in comparison with normolipidemic subjects. The elevation of t-PA was presented only in patients with simultaneously elevated TG and apoB. The significant increase of IMT confirmed in the patients with DLP4 reveals individuals with the highest risk for atherosclerosis manifestation.

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“…1 The expression of THBD gene reflects endothelial activation and damage. 2,3 Previous studies of the role of soluble THBD in the risk of coronary heart disease (CHD) have been controversial. A recent report suggested that soluble THBD may not represent an independent risk marker.…”

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confidence: 99%

Thrombomodulin Gene Polymorphisms and Haplotypes and the Risk of Cardiovascular Events

Auro

Komulainen

Alanne

et al. 2006

ATVB

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Background-Thrombomodulin is an anticoagulant expressed during endothelial activation and damage. To address the potential role of allelic variants of thrombomodulin gene in the pathogenesis of cardiovascular diseases, we analyzed in a prospective follow-up study 8 single-nucleotide polymorphisms (SNPs) across the thrombomodulin locus, covering all common (Ͼ5%) haplotypes. Methods and Results-Two separate, stratified random samples of men and women 25 to 74 years of age were examined in Finland in 1992 and 1997. The total sample size was 14 140 individuals, with 7 (1997 cohort) to 10 (1992 cohort) years of follow-up. Altogether, 662 individuals had a history of cardiovascular events already at baseline. During the follow-up, 401 incident coronary events and 148 incident ischemic strokes were observed. The alleles and common haplotypes of 8 SNPs were tested in Cox proportional hazards models using incident coronary events, incident ischemic strokes, and total mortality as end points. None of the SNPs or major SNP haplotypes showed consistent association with the end points analyzed in the combined data. Conclusions-Results from this prospective, population-based study suggest that common allelic variants of the thrombomodulin gene may not significantly contribute to the risk of cardiovascular events at the population level.

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Increased levels of endothelial haemostatic markers in patients with coronary heart disease

Cited by 23 publications

References 33 publications

Oxidative Stress – a Link between Endothelial Injury, Coagulation Activation, and Atherosclerosis in Haemodialysis Patients

Oxidative Stress – a Link between Endothelial Injury, Coagulation Activation, and Atherosclerosis in Haemodialysis Patients

Prothrombotic markers in asymptomatic dyslipidemic subjects

Thrombomodulin Gene Polymorphisms and Haplotypes and the Risk of Cardiovascular Events

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