Simvastatin but not ezetimibe reduces sympathetic activity despite similar reductions in cholesterol levels

The relationship between the sympatholytic effects of statins and their lipid-lowering activity remains unclear. Ezetimibe lowers cholesterol, but its sympatholytic activity is unknown. The purpose of study was to compare the influence of equipotent doses of simvastatin and ezetimibe on sympathetic activity. This randomized double-blinded study was performed in 22 hypertensive patients (age, 45.6 ± 2.2 years; female/male, 2/20) with untreated hypercholesterolemia. The subjects were administered 20 mg/d of simvastatin (n = 11) or 20 mg/d of ezetimibe (n = 11) for 6 weeks. Pre- and post-treatment measurements of muscle sympathetic nerve activity (MSNA), baroreceptor control of heart rate (baroreflex sensitivity), and impedance cardiography were recorded. Simvastatin and ezetimibe produced similar reductions of total (−58.0 ± 23.4 vs. −45.2 ± 17.2 mg/dL; P = .15, respectively) and low-density lipoprotein cholesterol (−52.6 ± 20.9 vs. −37.9 ± 17.6 mg/dL; P = .09, respectively). There was a significant difference in the effect of simvastatin and ezetimibe on muscle sympathetic nerve activity (−8.5 ± 5.1 vs. −0.7 ± 3.5 bursts/min; P = .0005). Simvastatin improved baroreflex sensitivity as compared with ezetimibe (10.0 ± 14.3 vs. −2.8 ± 6.1 ms/mm Hg; P = .01). There was no difference in the effect of both treatments on blood pressure, heart rate, cardiac output, stroke volume, total peripheral resistance, high-density lipoprotein, and triglycerides. Simvastatin reduced sympathetic activity via lipid-independent mechanisms, but ezetimibe exerts no sympatholytic effects.     

我国农村地区高胆固醇血症患病情况分析

目的 了解我国农村居民高胆固醇血症（HC）的患病、知晓及治疗情况.方法 2013年到2014年期间,在全国4个县进行了心血管病危险因素调查,实际入选5402人,有效数据4982人.利用该资料计算我国35岁农村居民HC的患病、知晓及治疗率.结果 本调查发现我国35岁以上农村居民胆固醇边缘升高率为20.49％,HC的患病率为8.07％,知晓率为6.74％,治疗率为12.44％.HC的患病和知晓率均随着年龄的增加而升高.吸烟、肥胖及轻体力活动人群的HC患病率较高（P＜0.05）;吸烟、超重、中度体力活动及家庭收入较低的人群知晓率较低（P＜0.05）.重度体力活动、超重及肥胖人群的治疗率较高（P＜0.05）.多因素分析发现年龄,性别,体质指数,高血压及糖尿病与HC的患病相关.结论 我国35岁以上农村居民HC患病率呈上升趋势,而知晓率和治疗率很低,亟待采取相应干预策略降低血脂水平,减少心脑血管疾病的发生.     

JCL roundtable: Managing lipid disorders in young women

The roundtable discussion in this issue will focus on the problems faced by young women with lipid disorders. This is often the source of confusion for the patient and physician because the myth continues that young women do not have complications of atherosclerosis as a result of elevated blood cholesterol. The essential role of women in bearing children during the early years of adulthood also produces difficult decisions because the mother and fetus are usually experiencing similar exposure to therapeutic regimens. We are joined in this discussion by Drs. Pamela Morris of the Medical University of South Carolina and Robert Wild of the University of Oklahoma Health Sciences Center. Dr Morris is an Internist, and Dr Wild is an Obstetrician and Gynecologist. Both are board certified in clinical lipidology and are actively publishing in this field. We have recorded this roundtable discussion during the National Lipid Association Scientific Sessions held in New Orleans during May 2016.     

Ezetimibe and Rosuvastatin Combination Treatment Can Reduce the Dose of Rosuvastatin Without Compromising Its Lipid-lowering Efficacy

PurposeThe goal of this study was to compare the lipid-lowering efficacy of the combination of ezetimibe and low- or intermediate-intensity statin therapy versus that of high-intensity statin monotherapy.MethodsThis study is a post hoc analysis of an 8-week, randomized, double-blind, Phase III trial. Patients who had hypercholesterolemia and required lipid-lowering treatment were randomly assigned to 1 of 6 treatment groups: rosuvastatin 5 mg (R5, n = 68), rosuvastatin 10 mg (R10, n = 67), rosuvastatin 20 mg (R20, n = 69), and ezetimibe 10 mg combined with rosuvastatin 5 mg (R5 + E10, n = 67), rosuvastatin 10 mg (R10 + E10, n = 68), and rosuvastatin 20 mg (R20 + E10, n = 68) daily. The effects of coadministration of ezetimibe and a low dose of rosuvastatin on lipid parameters and the target achievement rate were compared between the R5 + E10 and R10 treatment groups, the R5 + E10 and R20 treatment groups, and the R10 + E10 and R20 treatment groups.FindingsReductions in total cholesterol, LDL-C, apolipoprotein B, the apolipoprotein B/A1 ratio, and non–HDL-C were not different between the R5 + E10 and R10 treatment groups (all, P > 0.017), the R5 + E10 and R20 treatment groups (all, P > 0.017), and the R10 + E10 and R20 treatment groups (all, P > 0.017). R5 + E10 treatment showed efficacy comparable to that of R10 or R20 in affording LDL levels <50% of the baseline level (R5 + E10 vs R10, 73.13% vs 62.69% [P = 0.1952]; R5 + E10 vs R20, 73.13% vs 73.91% [P = 0.9180]), LDL-C levels <70 mg/dL (R5 + E10 vs R10, 64.18% vs 55.22% [P = 0.2906]; R5 + E10 vs R20, 64.18% vs 62.32% [P = 0.8220]), and LDL-C levels <50% of the baseline level or <70 mg/dL (R5 + E10 vs R10, 77.61% vs 70.15% [P = 0.3255]; R5 + E10 vs R20, 77.61% vs 78.26% [P = 0.9273]). The R10 + E10 treatment group was better than the R20 treatment group in achieving the target LDL-C level <70 mg/dL (83.82% vs 62.32%; P = 0.0046), even among participants with a baseline LDL-C level >135 mg/dL (77.5% vs 48.8%, respectively; P = 0.0074).ImplicationsEzetimibe combined with low- or intermediate-intensity statin therapy has lipid-lowering efficacy comparable to or better than that of high-intensity rosuvastatin monotherapy. The results of the present study indicate that the combination treatment with ezetimibe is advantageous in that it permits dose reduction of rosuvastatin without compromising the lipid-lowering efficacy of rosuvastatin. ClinicalTrials.gov identifier: NCT02205606.     

A comparative study of the in vitro antioxidant activity of statins

Background: Treatment of hypercholesterolemia with statins is remarkably effective in cardiovascular prevention. This has led to the hypothesis that these drugs may act on the atherosclerotic plaque by mechanism(s) independent of the reduction of serum cholesterol levels. The aim of this study was to assess the total antioxidant activity of the most prescribed statins: fluvastatin, atorvastatin, pravastatin and simvastatin. Methods: We measured the in vitro antioxidant activity of statins as their ability to antagonize the oxidation of -keto-γ-methiolbutyric acid by both hydroxyl and peroxyl radicals. The results are expressed as Total Oxyradical Scavenging Capacity (TOSC) units. Uric acid and Trolox were used as the reference antioxidants. Results: The scavenging capacity towards hydroxyl radicals was highest for simvastatin (3375±112 U/mg), a value 270.2% higher (P<0.0001) compared to uric acid (reference antioxidant vs. hydroxyl radicals, 1249±71 U/mg). Among the tested statins, fluvastatin exhibited the highest anti-peroxyl radical antioxidant capacity (8755±187 U/mg) which appeared 50% lower (P<0.0001) compared to Trolox (reference antioxidant vs. peroxyl radicals, 17 460±379 U/mg). Conclusions: All the statins tested have intrinsic antioxidant activity with both anti-hydroxyl and peroxyl radical activity. Simvastatin was the most effective as an anti-hydroxyl radical antioxidant and fluvastatin as an anti-peroxyl radical antioxidant.     

伴刀豆球蛋白A刺激高胆固醇血症兔的单核细胞释放高水平的生长因子

复制高胆固醇血症（ｈｙｐｅｒｃｈｏｌｅｓｔｅｒｏｌｅｍｉａ，ＨＣ）兔模型，取其血液分离单核细胞（ｍｏｎｏｃｙｔｅｓ，ＭＣ），培养于含或不含伴刀豆球蛋白Ａ（ｃｏｎｃａｎａｖａｌｉｎＡ，ＣｏｎＡ）的无血清ＤＭＥ／Ｆ１２培养基中，收集不同条件的ＭＣ条件培养基（ＭＣ－ｃｏｎｄｉｔｉｏｎｅｄｍｅｄｉｕｍ，ＭＣ－ＣＭ）。并检测其促有丝分裂活性。结果表明，经ＣｏｎＡ激活的ＨＣ兔的ＭＣ－ＣＭ刺激３Ｈ－ＴｄＲ掺入ＮＩＨ３Ｔ３     

L-精氨酸对高脂血症家兔血浆脂蛋白、一氧化氮和脂过氧化物的影响

用雄性新西兰白兔观察了Ｌ－精氨酸对高脂血症时血浆脂蛋白、血清一氧化氨、脂过氧化物和超氧化物歧化酶的影响。结果发现２％Ｌ－精氨酸与２％胆固醇同时喂养９０天，或喂养９０天以后４％Ｌ－精氨酸治疗９０天，均能有效地抑制高胆固醇所致的血清脂过氧化物的升高，提高高脂血症家兔血清超氧化物歧化酶活性，促进血管内皮细胞一氧化氮的释放。结果提示，Ｌ－精氨酸／一氧化氮可能有抗高脂血症家兔低密度脂蛋白氧化修饰的作用。     

Improvement in the endothelium-dependent relaxation in hypercholesterolemic rabbits treated with vitamin E

The authors studied the time course of the vitamin E mediated improvement in endothelium-dependent relaxation in hypercholesterolemic rabbits. A total of 40 male New Zealand white rabbits were randomly assigned to hypercholesterolemic (control) and vitamin E treated groups. The latter group was further divided in three subgroups in accordance with the duration of the vitamin E treatment (2, 4 or 6 days) at the end of the experiment. The dose of vitamin E utilized was 50 IU/day administered once a day by gavage. All the rabbits were fed a diet supplemented with cholesterol (0.5%) and coconut oil (2%) for 4 weeks. At the end of this period, the animals were sacrificed and the aorta removed for determination of the cholesterol and malondialdehyde (MDA) contents. The relaxation of the aortic strips in response to acetylcholine was also studied. In addition, the cholesterol and MDA contents of native and oxidized LDL were measured. At the end of the 4th week, the MDA level was significantly reduced in native and oxidized LDL in the rabbits treated with vitamin E for 2 days, while in aortic tissue a reduction was seen after 4 days of treatment. Endothelium-dependent relaxation improved significantly after 6 days of vitamin E administration, and there was a reduction in the total plasma and aortic cholesterol levels during this same period. We conclude that vitamin E at a dose of 50 IU/day for 6 days improves the endothelium-dependent relaxation seen in hypercholesterolemic rabbits. This effect may be mediated through an antioxidant action on LDL particles and on the aortic arterial wall.     

高胆固醇血症低密度脂蛋白受体基因点突变的研究

目的：建立低密度脂蛋白－受体（ＬＤＬ－Ｒ）基因点突变监测方法,从基因水平对３０例原发性高胆固醇血症患者进行筛选、明确诊断。 方法：将聚合酶链式反应－单链构象多态性（ＰＣＲ－ＳＳＣＰ）与银染技术相结合,用１９对引物对ＬＤＬ－Ｒ基因的全部１８个外显子进行检测,３０例患者中,对筛查出的突变用ＰＣＲ产物直接测序或克隆测序的方法明确突变的性质和位置。 结果：确立的ＰＣＲ－ＳＳＣＰ条件稳定,银染方法灵敏度高、重复性好,且避免了同位素污染。３０例患者中,发现１例定位于外显子１４的杂合子点突变患者,ＰＣＲ产物直接测序证实第６７１位密码子发生错义突变：ＣＣＣ→ＣＧＣ,导致脯氨酸→精氨酸;１例纯合子家族性高胆固醇血症患者外显子７发生点突变,克隆测序证实密码子３０８位发生错义突变：ＴＡＣ→ＴＧＣ,导致半胱氨酸→酪氨酸;２例杂合子患者外显子４的３’部分ＳＳＣＰ出现相同异常带型。查阅文献,测序证实的突变皆是新的突变。 结论：建立的ＰＣＲ－ＳＳＣＰ方法可用于高胆固醇血症患者ＬＤＬＲ基因点突变的筛检。研究结果从基因水平证实中国家族性高胆固醇血症患者ＬＤＬ－Ｒ基因突变具有多样性的特点。