Ignite Creation Date:
2024-05-05 @ 11:57 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00189085
Status:
COMPLETED
Last Update Posted:
2010-06-10
First Post:
2005-09-12
Brief Title:
Effects of Ezetimibe on Postprandial Hyperlipidemia and Endothelial Function
Sponsor:
UMC Utrecht
Organization:
UMC Utrecht
Study Overview
Official Title:
The Effects of Ezetimibe on Postprandial Hyperlipidemia and Endothelial Dysfunction in Patients With the Metabolic Syndrome
Status:
COMPLETED
Status Verified Date:
2004-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
In the present study the investigators are researching the effects of the cholesterol absorption inhibitor ezetimibe on postprandial lipemia and postprandial endothelial function in patients with the metabolic syndrome The lipid-lowering effect of high-dose statin monotherapy on fasting lipids is equal to the combination therapy of low-dose statin and ezetimibe
Detailed Description:
In patients at high risk for future cardiovascular events more intensive LDL cholesterol lowering with high doses statin therapy provides greater protection against death or major cardiovascular events than does a standard regimen Intensive LDL cholesterol lowering can be achieved by high dose statin treatment or with combination therapy of lower doses statin and ezetimibe However it is unclear whether this combination therapy results in the same or more beneficial effects on cardiovascular prognosis
The metabolic syndrome is a cluster of several vascular risk factors as abdominal obesity high blood pressure hypertriglyceridemia low HDL cholesterol and high fasting glucose The underlying pathophysiology is still not fully clarified but insulin resistance seems to be a main characteristic of this syndrome Subjects with the metabolic syndrome are at increased risk for the development of cardiovascular morbidity and mortality and type II diabetes The prevalence of the metabolic syndrome is high in patients with clinical manifestations of vascular diseases and is associated with more vascular damage in these patients
Insulin resistance is linked to endothelial dysfunction and decreased nitric oxide bioavailability by several mechanisms including inflammation as reflected by elevated high sensitive C Reactive Protein hs-CRP plasma levels disruption of insulin receptor signalling cascades increased production of cytokines and activation of the renin angiotensin system However other studies do not support an association between insulin resistance and endothelial function so this mechanism seems controversial
In the postprandial state insulin resistance is associated with hyperlipidemia Postprandial hyperlipidemia may be an important determinant of endothelial dysfunction as well Remnants of chylomicron and very low density lipoprotein metabolism impair endothelial dependent vasodilatation In line with the hypothesis that endothelial function can be used as a surrogate endpoint for cardiovascular morbidity therapeutic modulation of postprandial endothelial function may potentially contribute to prevention of cardiovascular disease in patients with the metabolic syndrome
Statin therapy modulates postprandial endothelial function but it is not known whether this is an indirect effect of lipid-lowering or a direct vascular effect of statins influencing the stability and bioavailability of NOS
AIMS In the present study we propose to investigate the effects of the cholesterol absorption inhibitor ezetimibe on postprandial lipemia and postprandial endothelial function in patients with the metabolic syndrome High-dose statin monotherapy has the same lipid-lowering effect on fasting lipids as the combination therapy of low dose statin and ezetimibe The latter may reduce postprandial lipemia more effectively and may therefore have beneficial effects on postprandial endothelial dysfunction
Ezetimibe is unlikely to have a direct vascular effect and therefore any observed change in vascular function is due to a change in postprandial lipemia As secondary objective of the study this enables us to differentiate between direct and indirect effects of statin therapy on postprandial endothelial function comparing modulation of postprandial endothelial function by monotherapy simvastatin with combination therapy of simvastatin and ezetimibe
Hypothesis With comparable reduction in fasting plasma lipids combination therapy of low-dose statin and ezetimibe reduces postprandial lipemia better than high-dose statin monotherapy This leads to better postprandial endothelial function in patients with the metabolic syndrome
Objectives
1 To determine the effects of combination therapy of low-dose statin and ezetimibe on postprandial hyperlipidemia compared to high-dose statin monotherapy
2 To determine the effects of combination therapy of low-dose statin and ezetimibe on postprandial endothelial dys-function compared to high-dose statin monotherapy
The metabolic syndrome is a cluster of several vascular risk factors as abdominal obesity high blood pressure hypertriglyceridemia low HDL cholesterol and high fasting glucose The underlying pathophysiology is still not fully clarified but insulin resistance seems to be a main characteristic of this syndrome Subjects with the metabolic syndrome are at increased risk for the development of cardiovascular morbidity and mortality and type II diabetes The prevalence of the metabolic syndrome is high in patients with clinical manifestations of vascular diseases and is associated with more vascular damage in these patients
Insulin resistance is linked to endothelial dysfunction and decreased nitric oxide bioavailability by several mechanisms including inflammation as reflected by elevated high sensitive C Reactive Protein hs-CRP plasma levels disruption of insulin receptor signalling cascades increased production of cytokines and activation of the renin angiotensin system However other studies do not support an association between insulin resistance and endothelial function so this mechanism seems controversial
In the postprandial state insulin resistance is associated with hyperlipidemia Postprandial hyperlipidemia may be an important determinant of endothelial dysfunction as well Remnants of chylomicron and very low density lipoprotein metabolism impair endothelial dependent vasodilatation In line with the hypothesis that endothelial function can be used as a surrogate endpoint for cardiovascular morbidity therapeutic modulation of postprandial endothelial function may potentially contribute to prevention of cardiovascular disease in patients with the metabolic syndrome
Statin therapy modulates postprandial endothelial function but it is not known whether this is an indirect effect of lipid-lowering or a direct vascular effect of statins influencing the stability and bioavailability of NOS
AIMS In the present study we propose to investigate the effects of the cholesterol absorption inhibitor ezetimibe on postprandial lipemia and postprandial endothelial function in patients with the metabolic syndrome High-dose statin monotherapy has the same lipid-lowering effect on fasting lipids as the combination therapy of low dose statin and ezetimibe The latter may reduce postprandial lipemia more effectively and may therefore have beneficial effects on postprandial endothelial dysfunction
Ezetimibe is unlikely to have a direct vascular effect and therefore any observed change in vascular function is due to a change in postprandial lipemia As secondary objective of the study this enables us to differentiate between direct and indirect effects of statin therapy on postprandial endothelial function comparing modulation of postprandial endothelial function by monotherapy simvastatin with combination therapy of simvastatin and ezetimibe
Hypothesis With comparable reduction in fasting plasma lipids combination therapy of low-dose statin and ezetimibe reduces postprandial lipemia better than high-dose statin monotherapy This leads to better postprandial endothelial function in patients with the metabolic syndrome
Objectives
1 To determine the effects of combination therapy of low-dose statin and ezetimibe on postprandial hyperlipidemia compared to high-dose statin monotherapy
2 To determine the effects of combination therapy of low-dose statin and ezetimibe on postprandial endothelial dys-function compared to high-dose statin monotherapy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None