ω-3羧酸对高危他汀治疗的残余高甘油三酯血症患者脂蛋白颗粒及其他心血管风险标志物的影响：一项随机、对照、双盲试验
Effects of omega-3 carboxylic acids on lipoprotein particles and other cardiovascular risk markers in high-risk statin-treated patients with residual hypertriglyceridemia: a randomized, controlled, double-blind trial.
作者信息
Dunbar Richard L, Nicholls Stephen J, Maki Kevin C, Roth Eli M, Orloff David G, Curcio Danielle, Johnson Judith, Kling Douglas, Davidson Michael H
机构信息
Division of Translational Medicine & Human Genetics, Perelman School of Medicine at the University of Pennsylvania, 3600 Spruce Street, 8046 Maloney Building, Philadelphia, PA, 19104-2699, USA.
South Australian Health & Medical Research Institute, University of Adelaide, Adelaide, Australia.
出版信息
Lipids Health Dis. 2015 Sep 2;14:98. doi: 10.1186/s12944-015-0100-8.
BACKGROUND
This study examined the effects of a mixture of highly bioavailable omega-3 carboxylic acids (OM3-CA) on nuclear magnetic resonance spectroscopy-assessed lipoprotein particle concentrations and sizes and other cardiovascular risk markers in statin-treated patients with fasting triglycerides (TG) ≥ 2.3 mmol/L (200 mg/dL) and <5.6 mmol/L (500 mg/dL) and at high cardiovascular risk.
METHODS
After a diet lead-in and statin-stabilization period, 647 patients were randomly assigned to receive capsules of control (olive oil, OO) 4 g/d, OM3-CA 2 g/d (plus OO 2 g/d), or OM3-CA 4 g/d for 6 weeks.
RESULTS
Compared with OO, low-density lipoprotein (LDL) particle size was increased with OM3-CA 2 g/d (p < 0.01) and 4 g/d (p < 0.001), and very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) particle sizes were decreased with both OM3-CA dosages vs. OO (p < 0.001 and p < 0.05 for VLDL and HDL, respectively). Total VLDL/chylomicron remnant particle concentration was reduced by 8.5 and 16.0 % with OM3-CA 2 and 4 g/d, respectively, vs. a 6.9 % reduction with OO (p < 0.001 for OM3-CA 4 g/d vs. OO). Total HDL particle concentration was also reduced by 1.5 and 3.2 % with OM3-CA 2 and 4 g/d, respectively, vs. a 0.6 % increase with OO (at least p < 0.05 for both comparisons). Changes in total LDL particle concentration were not significantly different for OO vs. OM3-CA at either dosage. Apolipoprotein (Apo) CIII levels decreased by 7.6 and 13.1 % with OM3-CA 2 and 4 g/d, respectively, vs. 3.2 % with OO (p < 0.001 for OM3-CA 4 g/d vs. OO). Lipoprotein-associated phospholipase A2 (Lp-PLA2) mass was reduced by 6.2 and 10.7 % with OM3-CA 2 and 4 g/d, respectively, vs. a 0.1 % increase with OO (p < 0.001 for both vs. OO). There were no significant differences between treatments in high-sensitivity C-reactive protein responses.
CONCLUSION
OM3-CA were associated with shifts in lipoprotein particle sizes and concentrations, and reductions in Apo CIII and Lp-PLA2, in patients with hypertriglyceridemia while taking a statin.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier NCT01408303.
背景
本研究探讨了高生物利用度ω-3羧酸混合物（OM3-CA）对经核磁共振波谱评估的脂蛋白颗粒浓度和大小以及其他心血管风险标志物的影响，研究对象为接受他汀类药物治疗、空腹甘油三酯（TG）≥2.3 mmol/L（200 mg/dL）且<5.6 mmol/L（500 mg/dL）、心血管风险较高的患者。
方法
经过饮食导入期和他汀类药物稳定期后，647例患者被随机分配，分别接受每日4 g的对照胶囊（橄榄油，OO）、每日2 g的OM3-CA（加每日2 g的OO）或每日4 g的OM3-CA，为期6周。
结果
与OO相比，每日2 g（p<0.01）和4 g（p<0.001）的OM3-CA可使低密度脂蛋白（LDL）颗粒大小增加，两种剂量的OM3-CA与OO相比，极低密度脂蛋白（VLDL）和高密度脂蛋白（HDL）颗粒大小均减小（VLDL和HDL分别为p<0.001和p<0.05）。与OO使总VLDL/乳糜微粒残余颗粒浓度降低6.9%相比，每日2 g和4 g的OM3-CA分别使其降低8.5%和16.0%（每日4 g的OM3-CA与OO相比，p<0.001）。与OO使总HDL颗粒浓度增加0.6%相比，每日服用2 g和4 g的OM3-CA分别使其降低1.5%和3.2%（两种比较均至少p<0.05）。两种剂量的OM3-CA与OO相比，总LDL颗粒浓度的变化均无显著差异。载脂蛋白（Apo）CIII水平在每日服用2 g和4 g的OM3-CA时分别降低7.6%和13.1%，而在服用OO时降低3.2%（每日4 g的OM3-CA与OO相比，p<0.001）。脂蛋白相关磷脂酶A2（Lp-PLA2）质量在每日服用2 g和4 g的OM3-CA时分别降低6.2%和10.7%，而在服用OO时增加0.1%（两种与OO相比均p<0.001）。各治疗组之间高敏C反应蛋白反应无显著差异。
结论
在服用他汀类药物的高甘油三酯血症患者中，OM3-CA与脂蛋白颗粒大小和浓度的改变以及Apo CIII和Lp-PLA2的降低有关。
试验注册
ClinicalTrials.gov标识符NCT01408303。
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