Antioxidant Supplements Block the Response of HDL to Simvastatin-Niacin Therapy in Patients With Coronary Artery Disease and Low HDL

Cheung, Marian C.; Zhao, Xue Qiao; Chait, Alan; Albers, John J.; Brown, B. Greg

doi:10.1161/hq0801.095151

Cited by 177 publications

(102 citation statements)

References 54 publications

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“…27 A recent angiographic study has indicated that antioxidant supplementation to lipid-lowering therapy prevented HDL-C elevation and was associated with a worse coronary angiographic outcome; 28,29 conversely, a predominant increase of HDL-C by gemfibrozil without a major reduction in LDL-C levels was associated with a significant reduction in the rate of coronary events. 30 Finally, patients with low HDL-C benefitted most when treated with fluvastatin in the Lipoprotein and Coronary Atherosclerosis Study (LCAS).…”

Section: Discussionmentioning

confidence: 99%

Haplotypes of the cholesteryl ester transfer protein gene predict lipid-modifying response to statin therapy

Winkelmann¹,

Hoffmann

Nauck

et al. 2003

Pharmacogenomics J

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Cholesteryl ester transfer protein (CETP) plays a central role in high-density lipoprotein (HDL) metabolism. Single nucleotide polymorphisms (SNPs) and haplotypes in the CETP gene were determined in 98 patients with untreated dyslipidemias and analyzed for associations with plasma CETP and plasma lipids before and during statin treatment. Individual CETP SNPs and haplotypes were both significantly associated with CETP enzyme mass and activity. However, only certain CETP haplotypes, but not individual SNPs, significantly predicted the magnitude of change in HDL cholesterol (HDL-C) and triglycerides. After adjusting for covariates and multiple testing, the TTCAAA haplotype showed a gene-dose effect in predicting the HDL-C increase (P¼0.03), while the TTCAAAGGG and AAAGGG haplotypes predicted a decrease in triglycerides (P¼0.04 both). This is the first study to demonstrate that SNP haplotypes derived from allelic SNP combinations in the CETP gene were more informative than single SNPs in predicting the response to lipid-modifying therapy with statins. The Pharmacogenomics Journal (2003) 3, 284-296, doi:10.1038/sj.tpj.6500195Keywords: cholesteryl ester transfer protein; HDL-cholesterol; triglycerides; haplotype; single nucleotide polymorphism; statin INTRODUCTION Cholesteryl ester transfer protein (CETP) mediates the transfer of neutral lipids between lipoproteins and plays a central role in high-density lipoprotein (HDL) metabolism. CETP transfers cholesteryl esters associated with HDL to triglyceride-rich lipoproteins, facilitating the clearance of cholesteryl esters from plasma. 1 Although the potential contribution of CETP to reverse cholesterol transport suggests an antiatherogenic mode of action, knowledge of the physiologic role of CETP in lipoprotein metabolism remains incomplete. The overall effect of CETP on atherogenesis may vary depending on both metabolic context and molecular variation in the CETP gene. 2 Investigations of associations between genetic variants in CETP and cardiovascular phenotypes are numerous, but often conflicting in their findings. The Taq1B polymorphism of the CETP gene has been associated with plasma levels of CETP and HDL cholesterol (HDL-C) and with the risk of coronary heart disease (CHD). 3,4 The Taq1B polymorphism has also been shown to serve as a marker of lipoprotein response to dietary intervention. 5,6 Other studies have demonstrated a link between the CETP I405V gene polymorphism and HDL-C, but not with response to diet. 7,8 Several other single nucleotide polymorphisms (SNPs) in the

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Section: Discussionmentioning

confidence: 99%

Haplotypes of the cholesteryl ester transfer protein gene predict lipid-modifying response to statin therapy

Winkelmann¹,

Hoffmann

Nauck

et al. 2003

Pharmacogenomics J

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“…In 2001, however, two studies were published which questioned the benefit of the combined therapies. Patients treated with simvastatin, niacin and a combination of different antioxidants (400 IU bis in die (BID; twice a day) vitamin E, 500 mg BID vitamin C, 12.5 mg BID β-carotene and 50 mg BID selenium) profited less than the simvastatin and niacin groups as the protective increase in HDL2 with simvastatin plus niacin was attenuated by concurrent therapy with antioxidants [243,244] . Tousoulis et al [245] treated patients suffering from ischemic heart failure with low dose atorvastatin (10 mg/d) alone or in combination with 400 IU/d vitamin E and found that vitamin E impairs the positive effects of atorvastatin, on, for example, endothelial function or inflammatory response.…”

Section: Interactions With Pharmaceuticsmentioning

confidence: 99%

Complexity of vitamin E metabolism

Schmölz¹,

Birringer²,

Lorkowski³

et al. 2016

WJBC

175

138

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Bioavailability of vitamin E is influenced by several factors, most are highlighted in this review. While gender, age and genetic constitution influence vitamin E bioavailability but cannot be modified, life-style and intake of vitamin E can be. Numerous factors must be taken into account however, i.e. , when vitamin E is orally administrated, the food matrix may contain competing nutrients. The complex metabolic processes comprise intestinal absorption, vascular transport, hepatic sorting by intracellular binding proteins, such as the significant α-tocopherol-transfer protein, and hepatic metabolism. The coordinated changes involved in the hepatic metabolism of vitamin E provide an effective physiological pathway to protect tissues against the excessive accumulation of, in particular, non-α-tocopherol forms. Metabolism of vitamin E begins with one cycle of CYP4F2/CYP3A4-dependent ω-hydroxylation followed by five cycles of subsequent β-oxidation, and forms the water-soluble end-product carboxyethylhydroxychroman. All known hepatic metabolites can be conjugated and are excreted, depending on the length of their sidechain, either via urine or feces. The physiological handling of vitamin E underlies kinetics which vary between the different vitamin E forms. Here, saturation of the side-chain and also substitution of the chromanol ring system are important. Most of the metabolic reactions and processes that are involved with vitamin E are also shared by other fat soluble vitamins. Influencing interactions with other nutrients such as vitamin K or pharmaceuticals are also covered by this review. All these processes modulate the formation of vitamin E metabolites and their concentrations in tissues and body fluids. Differences in metabolism might be responsible for the discrepancies that have been observed in studies performed in vivo and in vitro using vitamin E as a REVIEW

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“…The apo A-I promoter is sensitive to the oxidative state (61), and some antioxidants at high concentrations can suppress apo A-I promoter activity in Hep G2 cells (62). Clinical trials have also found that antioxidants may partially blunt HDL induction by simvastatin-niacin combination therapy (63). The precise role of micronutrient status in the diabetes-related reduction of apo A-I expression is not known.…”

Section: Effects Of Micronutrients On Apo A-i Expressionmentioning

confidence: 99%

Transcriptional Control of Apolipoprotein A-I Gene Expression in Diabetes

2004

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Cardiovascular disease continues to be the leading cause of mortality in diabetes. One of the factors contributing to the increased risk is the high prevalence rate of low plasma concentrations of HDL cholesterol. Multiple potential mechanisms account for the cardioprotective effects of HDL and its main protein apolipoprotein (apo) A-I. The reduced plasma concentrations of HDL could be the result of increased fractional clearance of HDL and reduced expression of apo A-I. In animal models of diabetes and in cell cultures treated with high concentrations of glucose, apo A-I expression is reduced. In this review we will discuss the alterations in transcriptional control of apo A-I in diabetes. The role of select nutritional and hormonal alterations commonly found in diabetes will be reviewed. Specifically, we will review the literature on the effect of hyperglycemia, hypoinsulinemia, and ketoacidosis, as well as the role of various mediators of insulin resistance, such as fatty acids, cytokines, and prostanoids, on apo A-I promoter activity. Identifying the mechanisms that modulate apo A-I gene expression will aid in the new development of therapeutic agents that increase plasma apo A-I and HDL concentrations.

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Antioxidant Supplements Block the Response of HDL to Simvastatin-Niacin Therapy in Patients With Coronary Artery Disease and Low HDL

Cited by 177 publications

References 54 publications

Haplotypes of the cholesteryl ester transfer protein gene predict lipid-modifying response to statin therapy

Haplotypes of the cholesteryl ester transfer protein gene predict lipid-modifying response to statin therapy

Complexity of vitamin E metabolism

Transcriptional Control of Apolipoprotein A-I Gene Expression in Diabetes

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