Lovastatin Therapy in Hypercholesterolemia: Effect on Fibrinogen, Hemorrheologic Parameters, Platelet Activity, and Red Blood Cell Morphology

Beigel, Yitzhak; Fuchs, Jacob; Snir, Moshe; Green, Pnina; Lurie, Yoav; Djaldetti, M

doi:10.1002/j.1552-4604.1991.tb03729.x

Cited by 62 publications

(31 citation statements)

References 18 publications

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“…47,48 Because elevated fibrinogen levels represent a recognized risk factor for CAD and thrombosis and significantly affect plasma thrombogenicity, the effects of statins on fibrinogen concentrations have been studied extensively. It has been reported that these agents increase, 28,49 decrease, 34,50 or, in a majority of reports, have no effect on plasma fibrinogen levels. 24 -26,37-39,51, 52 Most, but not all, 34 of the studies, in which fibrinogen concentrations have been measured using the Clauss method, concluded that inhibition of HMG-CoA reductase did not affect fibrinogen concentrations.…”

Section: Fibrinogen and Fibrinmentioning

confidence: 96%

Statins and Blood Coagulation

Undas

Brummel‐Ziedins²,

Mann³

2005

ATVB

241

192

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Abstract-The 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors (statins) have been shown to exhibit several vascular protective effects, including antithrombotic properties, that are not related to changes in lipid profile. There is growing evidence that treatment with statins can lead to a significant downregulation of the blood coagulation cascade, most probably as a result of decreased tissue factor expression, which leads to reduced thrombin generation. Accordingly, statin use has been associated with impairment of several coagulant reactions catalyzed by this enzyme. Moreover, evidence indicates that statins, via increased thrombomodulin expression on endothelial cells, may enhance the activity of the protein C anticoagulant pathway. Most of the antithrombotic effects of statins are attributed to the inhibition of isoprenylation of signaling proteins. These novel properties of statins, suggesting that these drugs might act as mild anticoagulants, may explain, at least in part, the therapeutic benefits observed in a wide spectrum of patients with varying cholesterol levels, including subjects with acute coronary events. Key Words: statins Ⅲ blood coagulation Ⅲ thrombin Ⅲ protein C T he 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase inhibitors, the so-called statins, have been proven to be highly effective in the management of hyperlipidemia and the prevention of atherosclerotic vascular disease, especially coronary artery disease (CAD). 1,2 The therapeutic benefits from statin therapy, however, are only poorly correlated with cholesterol lowering, suggesting other mechanisms are at play. Mevalonate, the product of HMGCoA reductase, is the precursor of not only cholesterol but also isoprenoid compounds that permit the attachment of signaling proteins to the cell membrane. 3,4 Abundant experimental and clinical evidence in this rapidly expanding field has resulted in the widely accepted concept of cholesterol-independent pleiotropic effects produced by statins that include alteration of endothelial dysfunction, leading to increased nitric oxide (NO) bioavailability, atherosclerotic plaque stabilization, regulation of angiogenesis, reduction of the inflammatory response, and antithrombotic properties. [5][6][7] Apart from profibrinolytic and antiplatelet effects, reported in several studies, 5,7-9 increasing evidence indicates that the HMG-CoA reductase inhibitors also modulate the blood coagulation cascade at multiple levels, leading to reduced thrombogenicity.The activation of the extrinsic coagulation pathway initiated by an exposure or expression of tissue factor (TF) plays a key role in hemostasis (Figure). The localized process involves multiple components, including blood coagulation factors, platelets, blood cells, the endothelium, and sublayers of a damaged vessel. Platelets provide the catalytic surface for the formation of the procoagulant complexes; the intrinsic factor Xase (FIXa-FVIIIa) and prothrombinase (prothrombin, FXa-FVa). These complexes accelerate thrombin ge...

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Section: Fibrinogen and Fibrinmentioning

confidence: 96%

Statins and Blood Coagulation

Undas

Brummel‐Ziedins²,

Mann³

2005

ATVB

241

192

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“…However, these studies have generally failed to provide consistent results. For example, lovastatin use has been associated with both an increase and decrease in fibrinogen levels [19,20]. Similar inconsistencies have been reported with the use of pravastatin, atorvastatin, and simvastatin [8••,21].…”

Section: Thrombosismentioning

confidence: 62%

Other than potency, are all statins the same?

Abate

Chandalia²

2006

Curr Atheroscler Rep

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Statins have been shown to interact with metabolic pathways that potentially affect physiologic functions beyond cholesterol balance. We may broadly categorize non-lipid effects of statins as clinically favorable or clinically detrimental. Whether non-lipid effects of statins are of clinical significance and whether there are differences in non-lipid effects among statins remain points of major current controversy. This review evaluates the available information on potential differences among statins in non-lipid effects.

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“…One study showed an increase in platelet sensitivity to ADP in patients treated with lovastatin for 26 weeks, despite a significant decrease in their LDL cholesterol levels. 12 In contrast, another study evaluated platelet aggregation in patients treated with lovastatin for 1 year and found a significant decrease in ADP-induced platelet aggregation. 14 We studied platelet function by using collagen and TRA in all 4 monkey groups.…”

Section: Discussionmentioning

confidence: 98%

“…9 Platelet aggregability has been shown to decrease with decreasing levels of LDL in patients with familial hyperlipidemia and in normolipidemic males. 10,11 HMG-CoA reductase inhibitors, such as lovastatin and pravastatin, lower LDL cholesterol, 12,13 which should result in decreased platelet sensitivity to aggregation. However, the actual effect of HMG-CoA reductase inhibitors on platelets is unclear.…”

Section: Discussionmentioning

confidence: 99%

Combination of Fosinopril and Pravastatin Decreases Platelet Response to Thrombin Receptor Agonist in Monkeys

Hale

Craver

Berrier

et al. 1998

ATVB

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Abstract-Both angiotensin-converting enzyme (ACE) inhibitors and 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors have been shown to decrease cardiovascular morbidity and mortality. Results from clinical trials have suggested that HMG-CoA reductase inhibition might exert a beneficial effect independent of its lipid-lowering effect, and ACE inhibition may exert a benefit independent of blood-pressure lowering. To test the hypothesis that such an effect might be mediated by alteration in platelet reactivity, we studied 55 monkeys receiving both, 1, or neither of the ACE inhibitor fosinopril and the HMG-CoA reductase inhibitor pravastatin. Platelet responsiveness to collagen and to the thrombin receptor agonist (TRA) SFLRRN-NH 2 was determined by aggregometry. For each agonist, the maximum rate and extent of aggregation were measured for each dose, and the concentration required for half-maximal response (C 50 ) was determined. Each drug, when given alone, slightly decreased the dose of agonist required to produce 50% response in the rate and extent of platelet aggregation relative to control. The combination of the 2 drugs, however, produced a significant increase in the dose of TRA required to produce 50% response in the rate and extent of aggregation relative to either drug alone or the control group. This was not true for collagen. The magnitude of the change relative to the control group, 47% for rate and 30% for extent of aggregation, could confer considerable protection by changing the threshold for thrombin-induced platelet aggregation and, thus, decrease thrombosis. (Arterioscler Thromb Vasc Biol. 1998;18:1643-1646.)Key Words: angiotensin-converting enzyme inhibitors Ⅲ platelet aggregation Ⅲ 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors C ardiovascular disease is the leading cause of death in the United States. 1 Most of the morbidity and mortality of this disease results from the rupture of atherosclerotic plaques in the vessel wall. This event leads to exposure of the thrombogenic inner components of the plaque to circulating blood, resulting in platelet activation and aggregation and activation of the coagulation system. Subsequently, a thrombus forms.2 The use of angiotensin-converting enzyme (ACE) inhibitors and lipid-lowering drugs has decreased cardiovascular morbidity and mortality below that expected from the resulting mild reduction in blood pressure and minor reduction in severity of coronary stenosis.2-4 Therefore, in addition to their well-known actions, these drugs probably have other protective effects on the processes that lead to cardiovascular disease and thrombosis. It is possible that these drugs may affect platelet function.In this randomized trial, we studied platelet responsiveness to collagen and a thrombin receptor agonist (TRA) in monkeys that were treated with an ACE inhibitor, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, both drugs, or neither drug. Methods MaterialsThe highly purified peptide TRA SFLRRN-NH 2 (PMIS387) wa...

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Lovastatin Therapy in Hypercholesterolemia: Effect on Fibrinogen, Hemorrheologic Parameters, Platelet Activity, and Red Blood Cell Morphology

Cited by 62 publications

References 18 publications

Statins and Blood Coagulation

Statins and Blood Coagulation

Other than potency, are all statins the same?

Combination of Fosinopril and Pravastatin Decreases Platelet Response to Thrombin Receptor Agonist in Monkeys

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