Effect of Statins on Platelet PAR-1 Thrombin Receptor in Patients With the Metabolic Syndrome (From the PAR-1 Inhibition by Statins [PARIS] Study)

Serebruany, Victor L.; Miller, Michael; Pokov, Alex; Malinin, Alex I.; Lowry, David R.; Tanguay, Jean François; Hennekens, Charles H.

doi:10.1016/j.amjcard.2005.11.058

Cited by 65 publications

(54 citation statements)

References 26 publications

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“…The baseline ICH volume was higher in statin users in all "time to CT" subgroups ( Table 2) except in the 6-24 hour subgroups for which the number of patients using statin was very small 5 . The median baseline ICH was increased for lobar and infratentorial cases but it did not reach statistical significance for basal ganglia ICH.…”

Section: Resultsmentioning

confidence: 99%

“…Statin agents have been reported to selectively inhibit platelet G-coupled, α-thrombin protease-activated receptors (PAR-1), which are cellbound proteins that link platelet activation and thrombin formation. 5 In addition, statins might directly influence platelet membrane, resulting in decreased function. 4 Despite increased mean hematoma volume in statin users, we did not detect a difference of mortality between the two groups.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, statins have been associated with decreased platelet function via direct influence on platelet membrane and inhibition of PAR-1, which is a cell-bound protein that links platelet activation. [4][5][6] An exploratory analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial found that statins overall effect included an increase in the number of treated patients having hemorrhagic stroke (n 55 for active treatment vs n 33 for placebo) with an unadjusted HR 1.68. 7 The Heart Protection Study (HPS) earlier described this ABSTRACT: Background: Some studies have suggested an association between hypocholesterolemia and intracerebral hemorrhage (ICH).…”

mentioning

confidence: 99%

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Statins May Increase Intracerebral Hemorrhage Volume

Ricard

Garant

Carrier

et al. 2010

Can. j. neurol. sci.

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Several epidemiological studies have demonstrated an association between hypocholesterolemia and the incidence of intracerebral hemorrhage (ICH).1-3 HMG-CoA reductase inhibitors (statin) may theoretically increase the risk of cerebral hemorrhage, given its cholesterol-lowering effect. In addition, statins have been associated with decreased platelet function via direct influence on platelet membrane and inhibition of PAR-1, which is a cell-bound protein that links platelet activation. [4][5][6] An exploratory analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial found that statins overall effect included an increase in the number of treated patients having hemorrhagic stroke (n 55 for active treatment vs n 33 for placebo) with an unadjusted HR 1.68. 7 The Heart Protection Study (HPS) earlier described this ABSTRACT: Background: Some studies have suggested an association between hypocholesterolemia and intracerebral hemorrhage (ICH). In the SPARCL trial, statin use increased ICH risk. We tested the hypothesis that use of statins affects the volume of spontaneous ICH and contributes to the progression of ICH volume between baseline and follow-up CT scans. Methods: Consecutive cases of spontaneous ICH were reviewed. Secondary causes were excluded. We measured ICH volume on the baseline and follow-up CT scans using the AxBxC/2 method. Multivariate analysis and logistic regression modeling were used. The primary outcome was the ICH volume on the baseline CT scan. Secondary outcomes included volume variation between the baseline and the first follow up CT scans and death. Results: Of 303 subjects, 71 were taking a statin at the time of the ICH (23%). Statin users were significantly more likely to be younger, to have co-morbidities and take anticoagulant or anti-platelet medication. They also had a higher baseline ICH volume than non-statin users (median 31.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Statins May Increase Intracerebral Hemorrhage Volume

Ricard

Garant

Carrier

et al. 2010

Can. j. neurol. sci.

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“…PAR-1 is a thrombin receptor that is reduced in statin treated patients. [34,35] PAR-1 repression by all statins has been found to be nearly identical. [36] Simvastatin decreases the expression of tissue factor (TF) in a monocyte model of in vitro clotting.…”

Section: Thrombosismentioning

confidence: 89%

Spectrum of Pleiotropic Effects of Statins in Heart Failure

Mathur

Ramasubbu

Mann

2008

Heart Failure Clinics

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“…The influence of statins on platelet function has been investigated in patients at risk for cardiovascular disease, such as those with hypercholesterolemia, diabetes mellitus, or metabolic syndrome, and in patients with established atherosclerosis, such as those with peripheral artery disease or coronary heart disease. [24][25][26][27][28][29] Studies that lasted ≥30 days demonstrated that statins inhibit platelet function, as assessed by ex vivo tests of platelet aggregation or by analysis of circulating molecules released by platelets on activation, such as soluble CD40L or P-selectin. 25,26,29 At least 2 mechanisms appear to be involved, including downregulation of cyclooxygenase-1 activation and upregulation of nitric oxide synthase.…”

Section: Statins and Platelet Activationmentioning

confidence: 99%