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Articles
by
Ronald B. Goldberg |
Total Records (
5 ) for
Ronald B. Goldberg |
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John R. Guyton
,
Ronald B. Goldberg
,
Theodore Mazzone
,
Ruth S. Weinstock
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Adam Polis
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Elizabeth Rosenberg
and
Andrew M. Tershakovec
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BackgroundType 2 diabetes mellitus (T2DM) is associated with a high risk for coronary heart disease (CHD). A variety of lipoprotein and apolipoprotein (Apo) ratios have been proposed that may reflect the balance of cholesterol delivery and removal at the arterial wall and provide an assessment of CHD risk that is supplemental to low-density lipoprotein cholesterol (LDL-C), the primary guide for cholesterol-lowering therapy in patients at risk. ObjectiveTo examine changes in lipoprotein and apolipoprotein ratios in the VYTAL trial of hypercholesterolemic patients with T2DM. MethodsChanges in the ratios LDL-C/high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC)/HDL-C, non-HDL-C/HDL-C, and ApoB/ApoA-I were assessed in this randomized, double-blind, parallel-group study that enrolled T2DM patients with LDL-C ≥100 mg/dL for 6-week treatments with either the usual daily starting doses of atorvastatin (ATORVA) 10 or 20 mg or ezetimibe/simvastatin (EZE/SIMVA) 10/20 mg, or the next highest doses (ATORVA 40 mg, EZE/SIMVA 10/40 mg). Changes in lipoprotein and apolipoprotein ratios, prespecified exploratory endpoints, were analyzed using analysis of variance. ResultsEfficacy results were based on 1198 patients with sufficient data among 1229 randomized patients. Baseline lipoproteins, apolipoproteins, and ratios were comparable among treatment groups. EZE/SIMVA produced significantly greater reductions compared with ATORVA in each lipoprotein or apolipoprotein ratio at each dose comparison (P < 0.001). For example, reductions from baseline in TC/HDL-C were ATORVA 10 mg, −30.2%; ATORVA 20 mg −34.9%; EZE/SIMVA 10/20 mg, −41.6%; ATORVA 40 mg, −37.9%; and EZE/SIMVA 10/40 mg, −43.5%. Tolerability of the two treatments was similar. ConclusionFor the doses assessed, EZE/SIMVA was more effective compared with ATORVA in lowering the lipoprotein and apolipoprotein ratios that might be considered secondary measures of CHD risk. |
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Ruth S. Weinstock
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Ronald B. Goldberg
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John R. Guyton
,
Theodore Mazzone
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Adam Polis
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Joanne E. Tomassini
,
Jianxin Lin
,
Arvind Shah
and
Andrew M. Tershakovec
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BackgroundIn addition to low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non–HDL-C), apolipoprotein B (ApoB), and high-sensitivity C-reactive protein (hs-CRP) are considered predictive for cardiovascular disease in type 2 diabetes mellitus (T2DM) patients. ObjectiveTo assess the proportion of T2DM patients with hypercholesterolemia who attained the optional target level of LDL-C (<70 mg/dL) and additionally non-HDL-C (<100 mg/dL), ApoB (<90 mg/dL), and hs-CRP (<2 mg/L), following treatment with ezetimibe/simvastatin (E/S) vs atorvastatin (A). MethodsThis post-hoc analysis of a multicenter, randomized, double-blind, 6-week parallel study assessed the proportion of T2DM patients who attained specified LDL-C levels and non-HDL-C, ApoB, and hs-CRP with usual, recommended starting doses of E/S (10/20 mg) vs A (10 or 20 mg) and next highest doses of E/S (10/40 mg) vs A (40 mg) by logistic regression. Baseline triglyceride and hs-CRP effects were also evaluated. ResultsSignificantly higher percentages of patients treated with E/S compared to A achieved individual and concurrent target levels of LDL-C (<70 mg/dL), non-HDL-C (<100 mg/dL), and ApoB (<90 mg/dL) at all dose comparisons (P < 0.05 to P < 0.001). Baseline triglyceride levels had no effect on reaching LDL-C levels. Attainment of non-HDL-C (<100 mg/dL), and ApoB (<90 mg/dL) was lower at triglycerides ≥200 mg/dL than <200 mg/dL. Achievement of hs-CRP level (<2 mg/L) was comparable for both treatments. Significantly more patients attained both LDL-C (<70 mg/dL) and hs-CRP (<2 mg/L) at all E/S doses compared to A (P < 0.05 to P < 0.001), regardless of baseline CRP levels. ConclusionE/S provides a therapeutic option to T2DM patients for lowering not only LDL-C, but also non-HDL-C, ApoB, and hs-CRP. These factors may help guide assessment and treatment of cardiovascular disease risk in these patients. |
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Michael H. Davidson
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Christie M. Ballantyne
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Terry A. Jacobson
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Vera A. Bittner
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Lynne T. Braun
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Alan S. Brown
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W. Virgil Brown
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William C. Cromwell
,
Ronald B. Goldberg
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James M. McKenney
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Alan T. Remaley
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Allan D. Sniderman
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Peter P. Toth
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Sotirios Tsimikas
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Paul E. Ziajka
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Kevin C. Maki
and
Mary R. Dicklin
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The National Cholesterol Education Program Adult Treatment Panel guidelines have established low-density lipoprotein cholesterol (LDL-C) treatment goals, and secondary non-high-density lipoprotein (HDL)-C treatment goals for persons with hypertriglyceridemia. The use of lipid-lowering therapies, particularly statins, to achieve these goals has reduced cardiovascular disease (CVD) morbidity and mortality; however, significant residual risk for events remains. This, combined with the rising prevalence of obesity, which has shifted the risk profile of the population toward patients in whom LDL-C is less predictive of CVD events (metabolic syndrome, low HDL-C, elevated triglycerides), has increased interest in the clinical use of inflammatory and lipid biomarker assessments. Furthermore, the cost effectiveness of pharmacological intervention for both the initiation of therapy and the intensification of therapy has been enhanced by the availability of a variety of generic statins. This report describes the consensus view of an expert panel convened by the National Lipid Association to evaluate the use of selected biomarkers [C-reactive protein, lipoprotein-associated phospholipase A2, apolipoprotein B, LDL particle concentration, lipoprotein(a), and LDL and HDL subfractions] to improve risk assessment, or to adjust therapy. These panel recommendations are intended to provide practical advice to clinicians who wrestle with the challenges of identifying the patients who are most likely to benefit from therapy, or intensification of therapy, to provide the optimum protection from CV risk. |
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Ronald B. Goldberg
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Robert S. Rosenson
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Eric Hernandez-Triana
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Soamnauth Misir
and
Michael R. Jones
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BackgroundThe bile acid sequestrant colesevelam has been shown to significantly reduce low-density lipoprotein particle concentration (LDL-P) in adults with primary hyperlipidemia or type 2 diabetes mellitus (T2DM). ObjectiveTo assess the effect of initial combination therapy with metformin plus colesevelam on lipoprotein particles in patients with T2DM (secondary efficacy variables). MethodsThis 16-week, randomized, double-blind, placebo-controlled study enrolled drug-naive adults with T2DM, glycated hemoglobin 6.5%-10.0%, low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL, and triglycerides <500 mg/dL. Patients were randomized 1:1 to either open-label metformin (titrated to 1700 mg/day) plus double-blind colesevelam 3.75 g/day or open-label metformin plus double-blind placebo. ResultsIn total, 286 patients were randomized (metformin plus colesevelam [n = 145]; metformin plus placebo [n = 141]). Compared with metformin plus placebo, the combination of metformin plus colesevelam significantly reduced LDL-C (mean treatment difference: −16.3%), total cholesterol (−6.1%), non-high-density lipoprotein cholesterol (−8.3%), and apolipoprotein (apo) B (−8.0%) and significantly increased triglycerides (median treatment difference: 18.6%) and apoA-I (mean treatment difference: 4.4%; all P < .001). Metformin plus colesevelam significantly reduced total LDL-P (mean treatment difference: absolute change -186 nmol/L [percent change −11.7%]; both P < .0001), largely attributable to a reduction in small LDL-P, and increased total very-low-density lipoprotein particle concentration (mean treatment difference: absolute change 6 nmol/L; P = .03 [percent change 8.3%; P = .06]) and total high-density lipoprotein particle concentration (1.0 μmol/L; P = .03 [4.5%; P = .01]) versus metformin plus placebo. ConclusionInitial combination therapy with metformin plus colesevelam improved the atherogenic lipoprotein profile of patients with early T2DM by significantly reducing LDL-P. ClinicalTrials.gov identifier: NCT00570739. |
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