The Prothrombotic Paradox of Hypertension

Dielis, Arne W. J. H.; Smid, Machiel; Spronk, Henri M. H.; Hamulyák, Karly; Kroon, Abraham A.; Cate, Hugo Ten; Leeuw, Peter W. de

doi:10.1161/01.hyp.0000193538.20705.23

Cited by 85 publications

(55 citation statements)

References 71 publications

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“…However, the renin-angiotensin system activates both coagulation and fibrinolytic pathways by increasing TF expression and plasma plasminogen activator inhibitor -1 levels. 16 These interesting interrelationships deserve a detailed investigation in the future.…”

Section: Discussionmentioning

confidence: 98%

“…14,15 Once exposed to injuries, such as, high blood pressure or increased shear stress, their procoagulant activity prevails. 16,17 Although intensive exercise was shown to be associated with increased coagulability through a mechanism involving endothelial activation, 18 virtually no data are available regarding the effect of still standing on the coagulation cascade.…”

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confidence: 99%

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Orthostatic Hypercoagulability

et al. 2008

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Abstract-Orthostatic stress causes significant plasma shift and raises transmural pressure in lower extremities, resulting in an increase in endothelial activation and plasma proteins concentrations, possibly including coagulation factors. This may lead to activation of the coagulation system during standing. To test this hypothesis, we recruited 18 healthy volunteers (9 females and 9 males; mean age: 25Ϯ1.2 years; body mass index: 21.7Ϯ0.5 kg/m 2 ). Hemodynamics, plasma shift (extrapolated from sequential hematocrit concentration), plasma proteins, and coagulation tests, including procoagulants; fibrinogen, factor V, and factor VIII activity; prothrombin fragments 1 and 2; and endothelial activation-related factors (tissue factor and von Willebrand factor), as well as protein C global pathway, were determined at rest supine and at 15 minutes, 30 minutes, and 60 minutes of still standing. Thirty minutes of standing caused a decrease in plasma volume by 12.0Ϯ0.5% and an increase in plasma protein by 13.0Ϯ0.7%. Fibrinogen, factor V, and factor VIII activity rose by 12.0Ϯ1.2%, 13.0Ϯ1.0%, and 40.0Ϯ6.0% (PϽ0.002 for all), respectively. Prothrombin fragments 1 and 2 were elevated by 150.0Ϯ30.0%. Tissue factor and von Willebrand factor increased by 30.0Ϯ9.0% and 17.4Ϯ51.0% (PϽ0.02 for both), respectively. However, protein C assay results decreased from 0.95Ϯ0.20 to 0.83Ϯ0.16 (PϽ0.001). We hereby introduce a novel physiological mechanism, "orthostatic procoagulation," that should be considered during coagulation tests. Furthermore, it could be extrapolated to the pathophysiology of stasis and venous thromboembolism.

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Section: Discussionmentioning

confidence: 98%

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confidence: 99%

Orthostatic Hypercoagulability

et al. 2008

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“…89,90 Hypertension increases shear stress leading to activation of NFκB and Egr-1, and subsequently to upregulation of TF gene expression. 91,92 Angiotensin-convertingenzyem (ACE) inhibitors downregulate TF expression in vivo, 93 while angiotensin II upregulates it in vascular cells via the angiotensin II type 1 receptor. 94 …”

Section: Hypertensionmentioning

confidence: 99%

Tissue Factor and Cardiovascular Disease: Quo Vadis?

Berndt

Tanner

Lüscher

2010

Circ J

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The coagulation cascade represents a system of proteases responsible to maintain vascular integrity and to induce rapid clot formation after vessel injury. Tissue factor (TF), the key initiator of the coagulation cascade, binds to factor VIIa and thereby activates factor IX and factor X, resulting in thrombus formation. Different stimuli enhance TF gene expression in endothelial and vascular smooth muscle cells. In addition to these vascular cells, TF has recently been detected in the bloodstream in circulating cells such as leukocytes and platelets, as a component of microparticles, and as a soluble, alternatively spliced form of TF. Various cardiovascular risk factors like hypertension, diabetes, and dyslipidemia, increase levels of TF. In line with this observation, enhanced vascular TF expression occurs during atherogenesis, particularly in patients with acute coronary syndromes. (Circ J 2010; 74: 3 - 12)

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“…20 Experimental studies indicated that inhibition of RAS by angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker resulted in an improvement of fibrinolytic balance or downregulation of tissue factor synthesis. 20 A clinical study by Koh et al 21 revealed that angiotensin II receptor blockade using candesartan, losartan, irbesartan reduced PAI-1 and tissue factor activity in hypertensive patients.…”

Section: Aortic Valve Sclerosis and Thrombin In Hypertension M Iida Ementioning

confidence: 99%

Association of aortic valve sclerosis with thrombin generation in hypertensive patients

et al. 2008

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Aortic valve sclerosis (AVS) may predispose to a prothrombotic state, as AVS is predictor of cardiovascular events in hypertensive populations. Thrombin exerts non-thrombotic effects such as vessel tone regulation, progression of atherosclerosis and stimulation of atrial natriuretic peptide (ANP) secretion. We hypothesized that hypertensive patients with AVS may have a persistently activated thrombin generation. We studied 234 asymptomatic never-treated hypertensive patients (73 of them with AVS). Prothrombin F1 þ 2 (F1 þ 2), as a marker of thrombin generation and fibrin D-dimer, as a marker of thrombus formation, ANP and brain natriuretic peptide (BNP) were measured. Presence of AVS, aortic jet velocity and left ventricular diameter at diastole were determined by echocardiography. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease formula. F1 þ 2 (median and interquartile range (IQR) ¼ 1.05, 0.87-1.38 nM vs 0.93, 0.72-1.16) and ANP (22, 14-37 pg ml À1 vs 17, 11-25) levels were greater, and glomerular filtration rate values (65 ± 9 ml min À1 /1.73 m 2 vs 68 ± 11) were lower in hypertensive patients with AVS than in those without AVS. F1 þ 2 (odds ratio, 95% CI ¼ 2.94, 1.07-8.6) was independently associated with AVS after being adjusted for age, gender and the variables of cardiorenal functions measured. After 6 months of treatment using valsartan, F1 þ 2 levels remained elevated in hypertensive patients with AVS (1.14, 0.83-1.42 nM vs 1.07, 0.84-1.5, n ¼ 19), but decreased in those without AVS (1.01, 0.85-1.31 vs 0.8, 0.84-1.78, n ¼ 27). Thrombin generation was associated with AVS in untreated hypertensive patients, and this association was persistent after blood-pressure-lowering treatment using valsartan.

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The Prothrombotic Paradox of Hypertension

Cited by 85 publications

References 71 publications

Orthostatic Hypercoagulability

Orthostatic Hypercoagulability

Tissue Factor and Cardiovascular Disease: Quo Vadis?

Association of aortic valve sclerosis with thrombin generation in hypertensive patients

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