Influence of Low HDL on Progression of Coronary Artery Disease and Response to Fluvastatin Therapy

Ballantyne, Christie M.; Herd, J. Alan; Ferlic, Laura; Dunn, Jon D.; Farmer, John A.; Jones, Peter H.; Schein, Jeffrey; Gotto, Antonio M.

doi:10.1161/01.cir.99.6.736

Cited by 193 publications

(92 citation statements)

References 34 publications

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“…30 Finally, patients with low HDL-C benefitted most when treated with fluvastatin in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). 31 No association was seen between changes in plasma lipids during statin therapy and individual SNPs, supporting our findings that the interaction of multiple CETP SNPs within a haplotype is a more powerful determinant of the clinical phenotype than are individual SNPs. This has also been demonstrated for the b2-adrenergic receptor and the response to a b2-bronchodilator.…”

Section: Discussionsupporting

confidence: 80%

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: Discussionsupporting

confidence: 80%

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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“…[1][2][3] Lipid lowering with statins in patients with elevated LDL improves, but does not normalize, endothelial vasomotor function. [27,35] Although the use of this class of medication markedly reduces clinical cardiovascular events, the majority of CAD events are not prevented in statin-treated patients. [14][15][16][17][18] Low levels of HDL increase the risk of the development of CAD, whereas high HDL levels are protective against this disease.…”

Section: Discussionmentioning

confidence: 99%

A novel mechanism for the beneficial vascular effects of high-density lipoprotein cholesterol: Enhanced vasorelaxation and increased endothelial nitric oxide synthase expression

Kuvin¹,

Rämet

Patel³

et al. 2002

American Heart Journal

223

133

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Background: Low levels of high-density lipoprotein (HDL) cholesterol increase the risk of coronary artery disease (CAD), and recent clinical studies suggest that interventions in low-HDL patients are beneficial. The purpose of this study was to examine the effect of increased HDL levels on endothelium-dependent vasodilation. Methods: We studied patients with CAD with a low-density lipoprotein (LDL) level of <100 mg/dL. Patients with an HDL level of <36 mg/dL were treated with niacin (n = 11), and patients with an HDL level of >36 mg/dL were followed as controls (n = 10). Baseline and 3-month follow-up studies of flow-mediated dilation (FMD) and blood lipid levels were obtained. Results: HDL levels increased from 30.1 ± 1.2 to 40.5 ± 1.2 mg/dL in the niacin-treated patients (P < .001) but remained unchanged in the control patients. At baseline, FMD was impaired in both the treated (6.5% ± 1%) and the control (7.3% ± 1%) patients compared with 10 healthy subjects (16% ± 2%, P < .01). After 3 months, FMD improved in the niacin-treated patients (11.8% ± 1%, P = .001) but remained unchanged in the control patients (6.2% ± 1%). Exposure of cultured human vascular endothelial cells to HDL in vitro enhanced expression of endothelial nitric oxide synthase (eNOS), as shown by immunoblotting. Conclusions:In patients with CAD and well-controlled LDL levels, elevation of HDL with niacin improves endothelial function. HDL increases eNOS protein expression in cultured vascular endothelial cells. Taken together, these observations suggest that HDL-mediated increases in eNOS expression may contribute to the observed enhancement in vasorelaxation and thus support a previously unrecognized mechanism for the beneficial cardiovascular effects of HDL.

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“…Khadem-Ansari et al 20 reported that the history of familial CHD was 27.3% of their CAD patients. Senaratne et al 32 35 found that more significant coronary artery lesions associated with low HDL-C patients (77.0%), Ballantyne et al 36 found that percentage of diameter stenosis was more in low HDL-C patients. Rahman et al 37 found low HDL-C associated with large lesions.…”

Section: Materials and Methodmentioning

confidence: 98%

Relationship between HDL-Cholesterol and Angiographic Severity of Coronary Artery Disease

Ahmed

Akhtaruzzaman²,

Rahman

et al. 2018

Bangladesh Heart J

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Abstract:Background: Dyslipidaemias is one of the major risk factor for Coronary artery diseases (CAD).There is an inverse correlation between high density lipoprotein cholesterol (HDL-C) and the risk of coronary artery disease. Understanding the angiographic characteristics of coronary artery diseases (CAD) in low and normal HDL-C patients and its association with severity of CAD is very important for future intervention. Although highdensity lipoprotein cholesterol (HDL-C) is well established predictor of future cardiovascular event, little information is available regarding its correlation with the prevalence and severity of angiographically evaluated coronary artery diseases (CAD). Conclusion: It may be concluded that low HDL-C level is associated with angiographically more severe coronary artery diseases reflected by vessels score and Friesinger score as compared to normal or high HDL-C level.

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Influence of Low HDL on Progression of Coronary Artery Disease and Response to Fluvastatin Therapy

Cited by 193 publications

References 34 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

A novel mechanism for the beneficial vascular effects of high-density lipoprotein cholesterol: Enhanced vasorelaxation and increased endothelial nitric oxide synthase expression

Relationship between HDL-Cholesterol and Angiographic Severity of Coronary Artery Disease

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