Effects of prescription omega-3-acid ethyl esters, coadministered with atorvastatin, on circulating levels of lipoprotein particles, apolipoprotein CIII, and lipoprotein-associated phospholipase A2 mass in men and women with mixed dyslipidemia

Maki, Kevin C.; Bays, Harold; Dicklin, Mary R.; Johnson, Susan L.; Shabbout, Mayadah

doi:10.1016/j.jacl.2011.09.001

Cited by 81 publications

(64 citation statements)

References 60 publications

(74 reference statements)

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“…The mechanism for increasing LDL-C may be an increased rate of conversion of very low-density lipoprotein to LDL particles and a reduction in the exchange of TAG for cholesteryl esters [39,43,44], which increases mean LDL particle size, generally without increasing the total LDL particle concentration [45,46]. In the present trial, there was no significant treatment effect of PDL-0101, which contains only EPA and no DHA, on mean LDL-C in the ITT population.…”

Section: Discussioncontrasting

confidence: 46%

Safety and lipid-altering efficacy of a new omega-3 fatty acid and antioxidant-containing medical food in men and women with elevated triacylglycerols

Maki

Geohas

Dicklin

et al. 2015

Prostaglandins, Leukotrienes and Essential Fatty Acids

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Section: Discussioncontrasting

confidence: 46%

Safety and lipid-altering efficacy of a new omega-3 fatty acid and antioxidant-containing medical food in men and women with elevated triacylglycerols

Maki

Geohas

Dicklin

et al. 2015

Prostaglandins, Leukotrienes and Essential Fatty Acids

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“…In subjects with mixed dyslipidemia, the use of either prescription omega-3 acid ethyl esters or placebo in combination with increasing dose of atorvastatin led to increased HDL-C levels by 2.4-6.3 % with no change in total HDL-P. There was however, a statistically significant reduction in the number of medium HDL particles concomitant with an increase in the number of small HDL particles [74].…”

Section: Therapeutic Interventionsmentioning

confidence: 90%

“…We recognized that an increase in HDL particles does not imply that these particles improve HDL functionality. In the Dallas Heart Study, HDL macrophage cholesterol efflux capacity was an independent predictor of incident Omega-3 fatty acids [73,74] 2.0 to 6.0 −1.2 to +1.0 0.6 to 1.1 Increase in small HDL-P Reduction in medium HDL-P Statins [75] 3.0 to 7.0 8.0 to 12.0 1.0 -2.0 Reduction in medium HDL-P Increase in large HDL-P Fibrates [76] 6.0 27.0 -2.0 Increase in small HDL-P Niacin [68] 28.1 9.8 5.9 na CETP inhibitors [13,71,72] 15.0 to 34.0 4.0 to 9.0 na Increase in large HDL-P Reduction in medium and small HDL-P Ezetimibe+Statin [69] 7.9 12.8 1.6 na Niacin+Ezetimbe+Statin [70] 29.4 16.2 7.5 na History of myocardial infarction (MI) (4.8 years) High HDL-C concentrations became positively associated with CHD risk (p<0.05) when adjusted for apo B and apo A1. In contrast, high HDL-P levels (≥45.7 μmol/l) remained inversely associated with CHD, in models adjusting for apo B and HDL-C.…”

Section: Hdl Measures and Clinical Endpointsmentioning

confidence: 99%

Underappreciated Opportunities for High-Density Lipoprotein Particles in Risk Stratification and Potential Targets of Therapy

Rosenson

Davidson

et al. 2015

Cardiovasc Drugs Ther

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The inverse relationship between high-density lipoprotein cholesterol (HDL-C) concentrations and coronary heart disease risk is well established. As a result, in recent years there have been significant resources focused on identifying therapies that raise HDL-C and ultimately reduce cardiovascular events. Unfortunately, a number of trials aimed at increasing HDL-C have failed to show improved outcomes, and hence, have cast doubt on the importance of HDL-C as a therapeutic target. HDL-C, however, is only one measure of HDL. HDL levels can also been estimated by quantifying apolipoprotein A-I (apoA-I) levels using enzyme immunoassay or by measuring HDL particle number (HDL-P) using nuclear magnetic resonance spectroscopy (NMR) or ion mobility. While these surrogate measures are correlated, they are not comparable. Lipoprotein-altering therapies have been shown to have different effects on HDL-C, apoA-I and HDL-P and several studies have demonstrated that HDL-P is a stronger predictor of coronary heart disease risk than HDL-C and/or apoA-I. This paper will review available evidence supporting the use of HDL-P as the biomarker of choice to assess the contribution of HDL to cardiovascular risk and as the primary goal of HDL-raising therapies.

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“…However, all currently available drugs have modest effects on apoC-III levels. For example, fi brates, tesaglitazar, pioglitazone, fi sh-oils, niacin, statins, and ezetimibe reduce apoC-III levels by 10-30% (15)(16)(17)(18)(19)(20)(21)(22)(23)(24). by guest, on May 11, 2018 www.jlr.org Downloaded from mechanisms discussed above.…”

Section: Downloaded Frommentioning

confidence: 99%

Reduction in lipoprotein-associated apoC-III levels following volanesorsen therapy: phase 2 randomized trial results

Yang

Lee

Choi

et al. 2016

Journal of Lipid Research

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ApoC-III is a 79 amino acid glycoprotein synthesized principally in the liver and associated with apoB-containing lipoproteins and HDL ( 1 ). apoC-III plays a key role in determining serum triglyceride levels and is a potent inhibitor of both the LPL-dependent and -independent pathways of triglyceride-rich lipoprotein (TRL) clearance. Thus, apoC-III inhibits the apoC-II-mediated activation of LPL and also inhibits hepatic lipase that plays an important role in the conversion of dense VLDL to IDL. Furthermore, apoC-III also inhibits TRL clearance by inhibiting receptor-mediated uptake of TRL by the liver ( 2 ).Recent work has shown that the CVD risk of circulating plasma apoC-III is not uniform, but rather dependent on its association with specifi c lipoproteins ( 3-5 ). This suggests that the effect of both LDL and HDL on CVD risk is context-dependent on the presence or absence of apoC-III. However, current methods to detect apoC-III on LDL or HDL utilize labor-intensive immunoprecipitation of apoC-III and/or ultracentrifugation methods that can only be Abstract Elevated apoC-III levels predict increased cardiovascular risk when present on LDL and HDL particles. We developed novel high-throughput chemiluminescent ELISAs that capture apoB, lipoprotein (a) [Lp(a)], and apoA-I in plasma and then detect apoC-III on these individual lipoproteins as apoCIII-apoB, apoCIII-Lp(a), and apoCIIIapoAI complexes, respectively. We assessed the effects on these complexes of placebo or 100-300 mg volanesorsen, a generation 2.0+ antisense drug that targets apoC3 mRNA in patients with hypertriglyceridemia, including familial chylomicronemia syndrome (n = 3), volanesorsen monotherapy (n = 51), and as add-on to fi brate (n = 26), treated for 85 days and followed for 176 days. Compared with placebo, volanesorsen was associated with an 82.3 ± 11.7%, 81.3 ± 15.7%, and 80.8 ± 13.6% reduction in apoCIII-apoB, apo-CIII-Lp(a), and apoCIII-apoA-I, respectively (300 mg dose; P < 0.001 for all), at day 92. Strong correlations in all assay measures were noted with total plasma apoC-III, chylomicron-apoC-III, and VLDL-apoC-III. In conclusion, novel high-throughput ELISAs were developed to detect lipoprotein-associated apoC-III, including for the fi rst time on Lp(a). Volanesorsen uniformly lowers apoC-III on apoB-100, Lp(a), and apoA-I lipoproteins, and may be a potent agent to reduce triglycerides and cardiovascular risk mediated by apoC-III.

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Effects of prescription omega-3-acid ethyl esters, coadministered with atorvastatin, on circulating levels of lipoprotein particles, apolipoprotein CIII, and lipoprotein-associated phospholipase A2 mass in men and women with mixed dyslipidemia

Cited by 81 publications

References 60 publications

Safety and lipid-altering efficacy of a new omega-3 fatty acid and antioxidant-containing medical food in men and women with elevated triacylglycerols

Safety and lipid-altering efficacy of a new omega-3 fatty acid and antioxidant-containing medical food in men and women with elevated triacylglycerols

Underappreciated Opportunities for High-Density Lipoprotein Particles in Risk Stratification and Potential Targets of Therapy

Reduction in lipoprotein-associated apoC-III levels following volanesorsen therapy: phase 2 randomized trial results

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