Lipid-Lowering Tx Doesn't Affect Postprandial Drop in HDL in Obese MetS Men
Lipid-Lowering Tx Doesn't Affect Postprandial Drop in HDL in Obese MetS Men
Introduction: The postprandial lipid metabolism in metabolic syndrome patients is disturbed and may add to the increased cardiovascular risk in these patients. It is not known whether postprandial high density lipoprotein-cholesterol (HDL-c) metabolism is also affected and whether this can be influenced by statin and/or ezetimibe treatment.
Methods: Prospective, randomized, double blind, crossover trial comparing simvastatin 80 mg with simvastatin/ezetimibe 10 mg/10 mg treatment for 6 weeks on postprandial HDL-c metabolism in 15, nonsmoking, male, obese metabolic syndrome patients (Adult Treatment Panel III, ATPIII). Only study medication was allowed. HDL-c concentrations, cholesteryl ester transfer (CET), CET protein (CETP) mass and adiponectin were measured before and after oral fat loading. ClinicalTrials.gov NCT00189085.
Results: Plasma HDL-c levels remained stable during continuous fasting following an overnight fast. Pre-fat load HDL-c concentrations without treatment, after simvastatin and simvastatin/ezetimibe treatment were 1.15 ± 0.04, 1.16 ± 0.05 and 1.11 ± 0.04 mmol/l. Fat load induced a 11% drop in HDL-c plasma levels; 1.02 ± 0.05 mmol/l (P < 0.001) which was not affected by either therapy. Triglyceride levels during fat load were similar after both treatments. Total CET increased from 9.73 ± 0.70 to 12.20 ± 0.67 nmol/ml/h (P = 0.004). Four hours after fat loading CETP mass was increased while adiponectin levels were decreased, irrespective of treatment.
Discussion: HDL-c levels decrease as CET increases after fat loading in obese metabolic syndrome patients. This is not influenced by either simvastatin or simvastatin/ezetimibe treatment. After fat loading, CETP mass and CET increased, and adiponectin decreased pointing towards a potential role for intra-abdominal fat. Decreased postprandial HDL-c levels may contribute to the increased cardiovascular risk in metabolic syndrome patients on top of already low HDL-c levels.
The clustering of cardiovascular risk factors associated with abdominal obesity (elevated blood pressure, elevated triglycerides and fasting glucose plasma levels and low plasma levels of high density lipoprotein-cholesterol (HDL-c) is often referred to as metabolic syndrome. The prevalence of metabolic syndrome is increasing and metabolic syndrome subjects are at increased risk for cardiovascular morbidity and mortality and for type 2 diabetes. The underlying pathophysiology of metabolic syndrome is not fully understood but insulin resistance and abdominal obesity, with associated alterations in adipocyte metabolism are main characteristics.
Low plasma HDL-c, associated with abdominal obesity and insulin resistance is a strong and independent risk factor for future cardiovascular events and mortality. Apolipoprotein A1 (ApoA1), an essential component of HDL particles, is synthesized in both liver and intestine. Interaction of ApoA1 with the ABCA1 receptor on the luminal side of the vascular endothelium results in removal of cholesterol from the vessel wall and subsequent maturation of HDL particles. A constant remodelling of HDL particles occurs through the action of both phospholipids transfer protein (PLTP) and cholesteryl ester transfer protein (CETP). CETP is, like adiponectin, visfatin, tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) produced by adipocytes and is the main facilitator of cholesteryl ester transfer (CET) in exchange of triglycerides between ApoA1 (HDL) and ApoB-containing lipoproteins (VLDL, IDL and LDL). In metabolic syndrome and insulin-resistant subjects, postprandial dyslipidemia is characterized by prolonged presence of atherogenic triglycerides-rich lipoproteins particles (TGR) in the circulation due to increased production of very low density lipoprotein (VLDL-c) and reduced lipolysis as a result of diminished lipoprotein lipase (LPL) activity. Little is known about postprandial HDL metabolism in insulin resistant and obese metabolic syndrome patients. In small studies in healthy subjects nonoverweight patients with coronary artery disease or diabetes and in habitual smoking subjects fat loading induced a decrease in plasma HDL-c levels.
Statins, alone or in combination with ezetimibe, are the most commonly used lipid-lowering therapies for cardiovascular risk reduction. In general, both therapies increase fasting HDL-c plasma levels between 3 and 9% and ApoA1 levels with 6%. However, atorvastatin did not affect a decrease in postprandial HDL-c plasma concentrations in male hypertriglyceridemic patients. The effect of statin alone or in combination with ezetimibe on postprandial HDL-c in obese metabolic syndrome patients is not known.
Aim of the present study was (i) to investigate the effects of an oral fat load on HDL-c metabolism in obese patients with metabolic syndrome and (ii) to compare the effects of high-dose simvastatin monotherapy with the combination of low-dose simvastatin with ezetimibe on post-fat load HDL-c metabolism.
Summary
Introduction: The postprandial lipid metabolism in metabolic syndrome patients is disturbed and may add to the increased cardiovascular risk in these patients. It is not known whether postprandial high density lipoprotein-cholesterol (HDL-c) metabolism is also affected and whether this can be influenced by statin and/or ezetimibe treatment.
Methods: Prospective, randomized, double blind, crossover trial comparing simvastatin 80 mg with simvastatin/ezetimibe 10 mg/10 mg treatment for 6 weeks on postprandial HDL-c metabolism in 15, nonsmoking, male, obese metabolic syndrome patients (Adult Treatment Panel III, ATPIII). Only study medication was allowed. HDL-c concentrations, cholesteryl ester transfer (CET), CET protein (CETP) mass and adiponectin were measured before and after oral fat loading. ClinicalTrials.gov NCT00189085.
Results: Plasma HDL-c levels remained stable during continuous fasting following an overnight fast. Pre-fat load HDL-c concentrations without treatment, after simvastatin and simvastatin/ezetimibe treatment were 1.15 ± 0.04, 1.16 ± 0.05 and 1.11 ± 0.04 mmol/l. Fat load induced a 11% drop in HDL-c plasma levels; 1.02 ± 0.05 mmol/l (P < 0.001) which was not affected by either therapy. Triglyceride levels during fat load were similar after both treatments. Total CET increased from 9.73 ± 0.70 to 12.20 ± 0.67 nmol/ml/h (P = 0.004). Four hours after fat loading CETP mass was increased while adiponectin levels were decreased, irrespective of treatment.
Discussion: HDL-c levels decrease as CET increases after fat loading in obese metabolic syndrome patients. This is not influenced by either simvastatin or simvastatin/ezetimibe treatment. After fat loading, CETP mass and CET increased, and adiponectin decreased pointing towards a potential role for intra-abdominal fat. Decreased postprandial HDL-c levels may contribute to the increased cardiovascular risk in metabolic syndrome patients on top of already low HDL-c levels.
Introduction
The clustering of cardiovascular risk factors associated with abdominal obesity (elevated blood pressure, elevated triglycerides and fasting glucose plasma levels and low plasma levels of high density lipoprotein-cholesterol (HDL-c) is often referred to as metabolic syndrome. The prevalence of metabolic syndrome is increasing and metabolic syndrome subjects are at increased risk for cardiovascular morbidity and mortality and for type 2 diabetes. The underlying pathophysiology of metabolic syndrome is not fully understood but insulin resistance and abdominal obesity, with associated alterations in adipocyte metabolism are main characteristics.
Low plasma HDL-c, associated with abdominal obesity and insulin resistance is a strong and independent risk factor for future cardiovascular events and mortality. Apolipoprotein A1 (ApoA1), an essential component of HDL particles, is synthesized in both liver and intestine. Interaction of ApoA1 with the ABCA1 receptor on the luminal side of the vascular endothelium results in removal of cholesterol from the vessel wall and subsequent maturation of HDL particles. A constant remodelling of HDL particles occurs through the action of both phospholipids transfer protein (PLTP) and cholesteryl ester transfer protein (CETP). CETP is, like adiponectin, visfatin, tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) produced by adipocytes and is the main facilitator of cholesteryl ester transfer (CET) in exchange of triglycerides between ApoA1 (HDL) and ApoB-containing lipoproteins (VLDL, IDL and LDL). In metabolic syndrome and insulin-resistant subjects, postprandial dyslipidemia is characterized by prolonged presence of atherogenic triglycerides-rich lipoproteins particles (TGR) in the circulation due to increased production of very low density lipoprotein (VLDL-c) and reduced lipolysis as a result of diminished lipoprotein lipase (LPL) activity. Little is known about postprandial HDL metabolism in insulin resistant and obese metabolic syndrome patients. In small studies in healthy subjects nonoverweight patients with coronary artery disease or diabetes and in habitual smoking subjects fat loading induced a decrease in plasma HDL-c levels.
Statins, alone or in combination with ezetimibe, are the most commonly used lipid-lowering therapies for cardiovascular risk reduction. In general, both therapies increase fasting HDL-c plasma levels between 3 and 9% and ApoA1 levels with 6%. However, atorvastatin did not affect a decrease in postprandial HDL-c plasma concentrations in male hypertriglyceridemic patients. The effect of statin alone or in combination with ezetimibe on postprandial HDL-c in obese metabolic syndrome patients is not known.
Aim of the present study was (i) to investigate the effects of an oral fat load on HDL-c metabolism in obese patients with metabolic syndrome and (ii) to compare the effects of high-dose simvastatin monotherapy with the combination of low-dose simvastatin with ezetimibe on post-fat load HDL-c metabolism.
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