Familial Hypercholesterolemia Among Young Adults With Myocardial Infarction

BackgroundThere are limited data on the prevalence and treatment of familial hypercholesterolemia (FH) among U.S. adults who experience a myocardial infarction (MI) at a young age.ObjectivesThis study aimed to evaluate the prevalence of clinically defined FH and examine the rates of statin utilization and low-density lipoprotein cholesterol (LDL-C) achieved 1-year post MI.MethodsThe YOUNG-MI registry is a retrospective cohort study that includes patients who experience an MI at or below age 50 years between 2000 and 2016 at 2 academic centers. Probable or definite FH was defined by the Dutch Lipid Clinic criteria. Outcomes included the proportion of patients classified as probable or definite FH, use of lipid-lowering therapy, and LDL-C achieved 1-year post MI.ResultsThe cohort consisted of 1,996 adults with a median age of 45 years; 19% were women, and 54% had ST-segment elevation MI. Probable/definite FH was present in 180 (9%) of whom 42.8% were not on statins prior to their MI. Of the 1,966 patients surviving until hospital discharge, 89.4% of FH patients and 89.9% of non-FH patients were discharged on statin therapy (p = 0.82). Among FH patients, 63.3% were discharged on high-intensity statin compared with 48.4% for non-FH patients (p < 0.001). At 1-year follow-up, the percent reduction in LDL-C among FH patients was ?44.4% compared with ?34.5% (p = 0.006) in non-FH patients. The proportion of patients with LDL-C ≥70 mg/dl was higher among FH patients (82.2%) compared with non-FH patients (64.5%; p < 0.001).ConclusionsClinically defined FH was present in nearly 1 of 10 patients with MI at a young age. Only two-thirds of FH patients were discharged on high-intensity statin therapy, and the vast majority had elevated LDL-C at 1 year. These findings reinforce the need for more aggressive lipid-lowering therapy in young FH and non-FH patients post-MI.     

人血浆中依折麦布浓度测定方法的不确定度评定

目的研究高效液相色谱-串联质谱法(HPLC-MS/MS)法测定人血浆中依折麦布浓度的不确定度评定方法。方法对依折麦布浓度测定全过程进行分析,包括测定精密度、称量、标准溶液的配制、固相萃取过程、标准曲线拟合等进行分析评定,根据各分量计算出合成不确定度,由合成不确定度及其分布求得扩展不确定度。结果人血浆中依折麦布浓度为0.20、2.0、16 ng·m L-1,在置信概率为95%时的扩展不确定度分别为(0.213±0.082)、(2.07±0.15)、(16.1±1.11)ng·m L-1。结论测定中的不确定度主要来自标准曲线的拟合过程,评价方法适用于血浆中依折麦布测定的不确定度评定。     

The implications of the ezetimibe and simvastatin in hypercholesterolemia enhances atherosclerosis regression trial: a return to first principles

To outward appearances, the publication of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial has led to a monolithic backlash against the use of ezetimibe by cardiologists for the treatment of hyperlipidemia. Rather than be swayed by popular opinion, we should each put the results of ENHANCE into context and ask the questions: should I put my trust in an imaging surrogate or in low‐density lipoprotein (LDL) cholesterol (LDL‐C), and how do the safety and efficacy of ezetimibe compare with other nonstatin lipid‐lowering agents? Copyright © 2008 Wiley Periodicals, Inc.     

依折麦布辛伐他汀片对兔腹主动脉粥样硬化斑块逆转作用的实验研究

目的：观察腹主动脉粥样斑块内炎性巨噬细胞和平滑肌细胞的表达情况,以探索依折麦布联合他汀类药物在逆转动脉斑块中的作用及机制。方法选取24只健康雄性新西兰大耳白兔,随机分为对照组（n＝8）和高胆固醇血症组（n＝16）。对照组给予普通饲料,喂养12周。高胆固醇血症组喂饲致动脉粥样硬化饲料（由普通颗粒饲料＋15g/L胆固醇＋100g/L猪油＋150g/L蛋黄粉组成）2周后行腹主动脉内膜球囊拉伤术,术后再随机分为模型亚组和依折麦布辛伐他汀（ES）亚组（给予5/10mg/（kg·d）每组8只,两亚组均继续喂饲致动脉粥样硬化饲料10周。喂养第12周时活杀动物,取腹主动脉进行石蜡切片。检测不同时间点脂质和脂蛋白,应用光学显微镜观察动脉粥样硬化进程,采用免疫组化方法分析巨噬细胞和平滑肌细胞在斑块处的表达。结果 ES亚组的血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）浓度明显低于模型亚组（P＜0.01）。病理检测显示两亚组及ES亚组斑块直径、斑块厚度和动脉内/中膜厚度经单因素方差分析,差异有统计学意义（P＜0.05）。免疫组化检测结果示ES亚组血管壁中巨噬细胞的表达量较模型亚组显著减少（P＜0.05）,而平滑肌细胞的表达量较模型亚组显著增多（P＜0.01）。结论 ES可能通过减少细胞外脂质的沉积,减少内膜和中膜巨噬细胞的数量和胆固醇的含量,增加胶原和平滑肌细胞面积,从而起到逆转斑块的作用。     

The effect of ezetimibe, administered alone or in combination with simvastatin, on lymphocyte cytokine release in patients with elevated cholesterol levels

Abstract. Krysiak R, Zmuda W, Okopien B (Medical University of Silesia, Katowice; and and Electrotherapy and Angiology Centre, Oswiecim, Poland). The effect of ezetimibe, administered alone or in combination with simvastatin, on lymphocyte cytokine release in patients with elevated cholesterol levels. J Intern Med 2012; 271 : 32–42. Objective. Studies assessing the extra‐lipid effects of ezetimibe have provided contrasting results. In the present study, we compared the effects of ezetimibe and simvastatin, administered alone or in combination, on the secretory function of human lymphocytes, systemic inflammation and endothelial function in subjects with elevated cholesterol levels. Methods. A prospective study involving a group of 178 ambulatory patients with isolated hypercholesterolaemia who were randomly assigned in a double‐blind fashion to 90 days of treatment with ezetimibe (10 mg), simvastatin (40 mg), ezetimibe (10 mg) plus simvastatin (40 mg) or placebo. A total of 170 patients completed the study. Main outcome measures. Lymphocyte cytokine release and plasma levels of high‐sensitivity C‐reactive protein (hsCRP) and intercellular adhesion molecule 1 (ICAM‐1). Results. Although both drugs reduced lymphocyte release of tumour necrosis factor‐α, interferon‐γ and interleukin‐2 in a lipid‐independent manner, only the effect of simvastatin was statistically significant (P < 0.001). This lymphocyte‐suppressing effect, which was accompanied by a decrease in plasma levels of hsCRP and ICAM‐1 (P < 0.001), was strongest in patients receiving both simvastatin and ezetimibe. There were no differences in lymphocyte‐suppressing, systemic anti‐inflammatory and endothelial protective effects of simvastatin between insulin‐resistant and insulin‐sensitive subjects, whereas the effects of ezetimibe and the combined treatment were greater in the former group of patients (P < 0.01 and P < 0.001, respectively). Conclusions. The results of this study indicate that simvastatin is superior to ezetimibe in producing lymphocyte‐suppressing, systemic anti‐inflammatory and endothelial protective effects in patients with elevated cholesterol levels. Hypercholesterolaemic patients with high cardiovascular risk may receive the greatest benefits from concomitant treatment with a statin and ezetimibe.     

依折麦布联合辛伐他汀对冠心病患者的调脂作用

目的:探讨依折麦布联合辛伐他汀对冠心病患者血脂及炎性因子的调节作用。方法: 选取2011年5月~9月我院收治的冠心病患者60例,随机分为试药组和对照组,每组各30例,试药组采用依折麦布(10 mg/d)联合辛伐他汀(20 mg/d),对照组单独使用辛伐他汀（40 mg/d）。在服药前、用药4周、用药8周时分别测定总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、肝功能、肾功能、肌酸激酶(CK)。结果: 与用药前基线水平相比,两组用药4周TC、LDL-C水平均显著下降（P<0.05）,治疗8周均进一步下降（P<0.01）,并且与对照组相比,试药组8周TC、LDL-C下降水平更显著（P<0.05）。两组患者的肝功能、肾功能、CK在用药后均无明显异常。结论: 依折麦布联合辛伐他汀能更有效地降低冠心病患者血脂水平。