Pharmacological Modulation of Platelet Function in Hypertension

Blann, Andrew D.; Nadar, Sunil; Lip, Gregory Y.H.

doi:10.1161/01.hyp.0000077901.84467.e1

Cited by 83 publications

(65 citation statements)

References 93 publications

(63 reference statements)

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“…increased reninangiotensin system stimulation and aldosterone production, increased arterial stiffness, shear stress and atherosclerotic disease) that have been linked with increased cardiovascular risk [29,30]. Moreover platelet activation resulting from increased oxidation, and shear stress, which were represented in hypertensive patients, might be second possible mechanism linking the RHTN with the elevated MPV [31]. Our study confirms the suggestion of the increase in MPV levels in hypertensive subjects especially in RHTN.…”

Section: Discussionsupporting

confidence: 86%

Assessment of Mean Platelet Volume in Patients with Resistant Hypertension, Controlled Hypertension and Normotensives

Surgit¹,

Püşüroğlu²,

Ertürk³

et al. 2015

Eurasian J Med

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Objective: Patients with resistant hypertension are at increased risk for cardiovascular events. Mean platelet volume (MPV) is an accepted biomarker of platelet activation and considered as a risk factor for cardiovascular disease. The aim of this study was to determine whether MPV levels are higher in resistant hypertensive (RHTN) patients than in controlled hypertensive (CHTN) patients and healthy normotensive controls. Materials and Methods Results:The mean platelet volume levels were significantly higher in RHTN group than in the CHTN and normotensive groups (p<0.001). In correlation analysis office systolic and diastolic blood pressure was positively correlated with MPV. Conclusion:Our study demonstrated that MPV, as an important indicator of platelet activation, was statistically higher in RHTN patients than in CHTN and in normotensive subjects. Elevated MPV levels may help to determine a high risk group for atherosclerosis in RHTN patients. Bulgular: Dirençli hipertansif grupta ortalama trombosit hacmi kontrollü hipertansif ve normotansif gruba göre istatistiksel olarak anlamlı olarak yüksek saptanmıştır (p<0,001). Korelasyon analizinde ofis sistolik ve diastoliktansiyonları ortalama trombosit hacmiyle pozitif korelasyon göstermekteydi. KeywordsSonuç: Çalışmamızda trombosit aktivasyonunun önemli belirteci olan ortalama trombosit hacmi dirençli hipertansif hastalarda diğer gruplara gore anlamlı olarak yüksek saptanmıştır. Artmış ortalama trombosit hacminin dirençli hipertansif hastalarda atheroskleroz açısından yük-sek riskli olanları değerlendirmede kullanılabileceği düşünülmektedir.Anahtar Kelimeler: Dirençli hipertansion, ortalama trombosit hacmi, kontrollü hipertansiyon

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Section: Discussionsupporting

confidence: 86%

Assessment of Mean Platelet Volume in Patients with Resistant Hypertension, Controlled Hypertension and Normotensives

Surgit¹,

Püşüroğlu²,

Ertürk³

et al. 2015

Eurasian J Med

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“…Other possibilities linking aliskiren and modulation of hemostasis may be due to compliment inhibition, 44 and/or hormonal disturbances. 45 Despite the fact, that in the in vitro setting aliskiren exhibited no pronounced changes in the hemostatic indices, it is possible that in the clinical ex vivo setting, chronic RAAS modulation will be associated with the mild inhibition of platelet activity, 46 coagulation 47 and enhanced fibrinolysis by blocking t-PA and PAI-1. 48 …”

Section: Discussionmentioning

confidence: 99%

“…During these last five decades the medical community has witnessed a tremendous evolution in antihypertensive pharmacotherapy, starting off with diuretics 2 and b-blockers 3 the subsequent discovery of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers, 4,5 and a concomitant improvement in hypertension control. As long as hypertension has been known as a major risk factor for vascular disease, 6 platelet activation and thrombus formation have also been identified as critical elements in the pathogenesis and natural course of cardiovascular disease and stroke. Conceptually, it may seem somewhat surprising that a condition characterized by hemodynamic vascular stress and abnormal blood flow under high pressure is associated with complications that are most often thrombotic rather than hemorrhagic.…”

Section: Introductionmentioning

confidence: 99%

Effects of aliskiren, a renin inhibitor, on biomarkers of platelet activity, coagulation and fibrinolysis in subjects with multiple risk factors for vascular disease

et al. 2008

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Aliskiren, an octanamide, is nonpeptide, low molecular weight, orally active renin inhibitor effectively preventing angiotensin and aldosterone release. This drug has been recently approved for the treatment of hypertension. Considering potential links between hypertension, platelets, the coagulation cascade and fibrinolysis we sought to evaluate the effect of aliskiren on human biomarkers of hemostasis. In vitro effects of whole blood preincubation with escalating concentrations of aliskiren (500, 1000 and 2000 ng ml À1) were assessed in 20 aspirin-naive volunteers with multiple risk factors for vascular disease. A total of 33 biomarkers were measured, of which 18 are related to platelet function, 12 to coagulation and 3 to fibrinolysis. Pretreatment of blood samples with aliskiren 500 ng ml À1 resulted in a significant increase of antithrombin-III (AT-III) activity (P ¼ 0.003). All other tested biomarkers were not significantly affected. Spiking whole blood with the higher aliskiren doses was associated with various trends in biomarker activity, where 1000 ng ml À1 concentration mostly decreased (7/33), and 2000 ng ml À1 mostly increased (6/33) some biomarkers. In the therapeutic concentration of 500 ng ml À1 aliskiren does not affect hemostatic biomarkers, except for a moderate but highly significant (P ¼ 0.003) increase of AT-III activity. Higher aliskiren doses were associated with more profound biomarker changes, but they are likely not to be clinically relevant since they show diverging (that is, both mild antiplatelet and platelet-activating) trends, and considering the 2-to 4-fold safety margin. It is suggested that antithrombotic properties of aliskiren be explored further in an ex vivo clinical setting.

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“…15 Indeed, some drug classes such as the calcium channel antagonists and ARBs might have direct effects on platelet biochemistry apart on reducing blood pressure. 31 Advances in pharmacology have led to antihypertensive drugs that have several effects over and beyond their blood pressure-lowering capacity, including action on thrombosis, inflammation and atherogenesis. Satisfactory blood pressure lowering can be achieved by most antihypertensive drugs, including the 'old' like beta-blockers or thiazide diuretics, as well as the 'new' agents, such as the ACE inhibitors, ARB or calcium antagonists.…”

mentioning

confidence: 99%

Are we content with lowering blood pressure alone, or should we be asking something more from the antihypertensive drugs we use?: effects of antihypertensive agents on fibrinolytic function

Roldán¹,

Marı́n

2004

J Hum Hypertens

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The fibrinolytic system plays an important role preventing intravascular thrombosis. The process of fibrinolysis is influenced by the intimate interactions between plasminogen activators (such as tissue plasminogen activator (t-PA) that promotes fibrinolysis) and inhibitors that modulate this activity (such as plasminogen activator inhibitor-1 (PAI-1)) -however, the net effect of the fibrinolytic system is mediated by activation of plasminogen to plasmin. 1 Plasmin is a serine protease that cleaves fibrin into soluble fragments, but shows other important functions, including increasing the activity of matrix metalloproteinases, 2 which degrade collagen and glycoproteins in atherosclerotic plaques, and thus, may be responsible for vascular remodelling. Plasmin also activates transforming growth factorbeta, an anti-inflammatory cytokine that inhibits migration and proliferation of smooth muscle cells, being of crucial importance in the early stages of atherosclerosis. 3 Structural and functional changes in vascular endothelium, which could be interpreted as a response to injury to the cell, may be involved in the development of vascular disease.Increasing evidence also suggests that an imbalance between t-PA and PAI-1 is of huge importance for the cardiovascular system. Indeed, established atherosclerotic disease is associated with changes in the endothelial function, as is the presence of its well-defined risk factors (eg smoking, diabetes, hypertension and hyperlipidaemia). 4 As endothelial cells release t-PA and PAI-1, it has been suggested that these could also be markers of endothelial cell damage or dysfunction. 5,6 Indeed, patients with cardiovascular risk factors demonstrate differences in t-PA and PAI-1 levels, and reduced activity of fibrinolytic function (lower t-PA activity and higher levels of PAI-1) has been reported in patients with hypertension and hypercholesterolemia, 7,8 as well as in diabetes. 9 Hence, raised concentrations of t-PA antigen have been associated with acute coronary syndromes 10,11 and stroke. 12 One aspect, which has to be taken into account, is the distinction between the measurement of activity and antigen levels of t-PA and PAI-1, as they represent very different things. The total amount of t-PA antigen that has been secreted is approximately equal to active t-PA plus t-PA/PAI-1 complex, being only a few percent of t-PA antigen functionally active. Hence, elevated t-PA antigen levels do not necessarily reflect an activation of the fibrinolytic system. Indeed, high plasma t-PA antigen concentrations are probably a marker for high PAI-1 concentrations and low intrinsic fibrinolytic activity. 13 Moreover, a relationship among t-PA antigen levels and markers of inflammation and endothelial damage has also been described. 14 While the blood vessels are exposed to high pressures in patients with hypertension, the main complications related to hypertension, such as myocardial infarction or stroke, are paradoxically thrombotic rather than haemorrhagic, the so-called

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Pharmacological Modulation of Platelet Function in Hypertension

Cited by 83 publications

References 93 publications

Assessment of Mean Platelet Volume in Patients with Resistant Hypertension, Controlled Hypertension and Normotensives

Assessment of Mean Platelet Volume in Patients with Resistant Hypertension, Controlled Hypertension and Normotensives

Effects of aliskiren, a renin inhibitor, on biomarkers of platelet activity, coagulation and fibrinolysis in subjects with multiple risk factors for vascular disease

Are we content with lowering blood pressure alone, or should we be asking something more from the antihypertensive drugs we use?: effects of antihypertensive agents on fibrinolytic function

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