升高高密度脂蛋白胆固醇药物的相关研究进展

目前已有流行病学资料明确提示,高密度脂蛋白胆固醇(HDL-C)水平与冠心病危险性呈负相关,低水平的HDL-C已被公认为动脉粥样硬化性疾病的独立危险因素之一。通过药物使HDL-C升高能否进一步降低心血管疾病的发病风险已成为近些年来临床试验关注的焦点。本文对目前已应用于临床或正在研究的具有升高HDL-C作用的四类药物,即他汀类、贝特类、烟酸及胆固醇酯转运蛋白(CETP)抑制剂的主要作用机制、临床研究进展等进行归纳和总结。其中,烟酸及CETP抑制剂升高HDL-C作用显著,尽管目前针对这两类药物的临床证据仍然较为匮乏,但有理由相信正在进行的几项国际大规模临床试验将为此提供重要的询证医学证据,其结果值得期待。     

原发性甲状腺功能减退症患者血清肌酸激酶及血脂的变化

目的:探讨原发性甲状腺功能减退症患者血清肌酸激酶、血脂变化及其与甲状腺功能的关系。方法:检测32例原发性甲减患者和20例健康体检者(对照组)的空腹血清三碘甲状腺原氨酸(T3)、甲状腺素(T4)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)、肌酸激酶(CK)、胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)。结果:原发性甲减患者血清肌酸激酶、胆固醇、甘油三酯和低密度脂蛋白胆固醇均明显高于对照组。甲减患者血清肌酸激酶活性与FT3、FT4、TSH具有显著相关性;胆固醇、甘油三酯与甲状腺功能各项指标无显著相关性。结论:原发性甲状腺功能减退症患者血清肌酸激酶、胆固醇、甘油三酯和低密度脂蛋白胆固醇显著升高;血清肌酸激酶活性与甲状腺功能有关。     

高密度脂蛋白胆固醇和冠心病的相关性研究

目的:探讨高密度脂蛋白胆固醇水平与冠心病的相关性.方法:选择427例经冠状动脉造影证实的冠心病患者作为病例组,并选择同期住院的冠脉造影结果阴性的306例非冠心病患者作为对照组,测定两组患者的血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、游离脂肪酸(FFA)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)、脂蛋白LP(a)等指标进行比较分析.结果:冠心病组与对照组比较,HDL-C水平显著降低(P＜0.05);在冠心病组中随着冠状动脉病变支数的增加,HDL-C逐渐下降(P＜0.05).多元Logistic回归分析,低HDL-C水平为冠心病的独立危险因素.结论:HDL-C与冠心病发生发展及冠脉病变程度呈显著负相关.TC/HDL-C可能对冠心病的诊断具有更好的预测价值.     

补肾复方对去势雌性恒河猴E2及HDL-C水平的影响

目的:探讨补肾复方对去势雌性恒河猴血清E2水平及HDL-C水平的影响.方法:将4只性成熟雌性恒河猴行双侧卵巢切除术,复制成人工绝经模型,然后按体重分层,随机分为补肾复方组和倍美力对照组,每组2只.每日灌胃1次,28 d为一疗程,连续给药3个疗程.观察给药前后血清HDL-C、E2水平变化.结果:两组问在不同的时间对血清E2水平的影响有统计学意义(P<0.05),但重复测量问和处理间无统计学惠叉(P>0.05).两组间在不同的时间、重复测量和处理间对HDL-C水平的影响无统计学意义(P>0.05).结论:补肾复方升高血清E2水平的作用,随着用药时间的延长,优于倍美力.     

高密度脂蛋白胆固醇与冠心病及其危险因素的回顾性分析

目的：探讨高密度脂蛋白胆固醇（HOE-C）与冠心病、冠心病危险因素的关系。方拔：将931份心脏科住院病例按HDL—C水平分为3组,小于1.04mmol／L为低水平组,1．04—1．54mmol／L为适当水平组,大于等于1．55mmol／L为高水平组,对3组资料进行回顾性分析。结果：甘油三酯（TG）、动脉粥样硬化指数、尿酸（UA）、血糖、急性心肌梗死和2型糖尿病患病率高水平组和（或）适当水平组明显低于低水平组（P〈0．05）,高水平组较适当水平组2型糖尿病和急性心肌梗死患病率、随机血糖、低密度脂蛋白（LDL）无显著差异（P〉0．05）。3组病人的住院天数、高血压、心律失常、冠心病患病率无明显差别（P〉0．05）。高水平组总胆固醇（TC）,收缩压最高（P〈0．05）。结论：虽然高水平、适当水平组较低水平组心血管保护作用明显。但高水平组较适当水平组心血管保护作用不显著。高密度脂蛋白胆固醇的质量比数量重要。     

Use of calcium supplements and the risk of coronary heart disease in 52–62-year-old women: The Kuopio Osteoporosis Risk Factor and Prevention Study

Background

To analyse prospectively the effect of calcium or calcium + D supplementation on coronary heart disease (CHD) in 52–62-year-old women.

Methods and results

10,555 52–62-year-old women from the population-based Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) who did not have CHD at baseline were followed for nearly 7 years in 1994–2001. Information about use of calcium supplements and health events was obtained from two repeated questionnaires in 1989 and 1994. Information about causes of death during the follow-up was obtained from the Statistics Finland. Information about CHD and other disease morbidity before and during the follow-up was obtained from the Registry of Specially Refunded Drugs of the Finnish Social Insurance Institution (SII). Cox's proportional-hazards models were used to estimate the risk of CHD morbidity related to the use of calcium supplements. At baseline, 2723 women reported current use of calcium or calcium + D supplementation. During the follow-up, CHD was diagnosed in 513 women. Compared to non-users of calcium/calcium + D supplements, the multivariate adjusted hazard ratio (HR) of CHD was 1.24 (95% CI 1.02–1.52) in women who used these supplements. The multivariate adjusted HR for CHD morbidity in postmenopausal women who used calcium/calcium + D supplements was 1.26 (95% CI 1.01–1.57).

Conclusions

Calcium or calcium + D supplementation appears to increase the risk of CHD among women before old age.     

血清脂蛋白与胃癌淋巴结转移及肿瘤分期的关系

目的观察胃癌患者血清高密度脂蛋白（HDL—C）、低密度脂蛋白（LDL—C）水平与肿瘤临床分期、淋巴结转移的关系。方法结合临床资料,回顾性分析2002年1月至2006年12月间收治的经病理学确诊的114例胃癌患者血清HDL—C、LDL—C的含量与临床病理特征之间的关系。结果血清HDL．C水平和胃癌分化程度、淋巴结转移及肿瘤的大小有密切关系（P=0．015,P=0．023,P=0．006）,TNMⅢ、1V期胃癌患者血清HDL—C水平明显低于Ⅰ、Ⅱ期患者（P=0．004,P=0．001）。结论术前测定患者血清HDL—C水平可能是预测胃癌淋巴结转移及判断胃癌病情进程的一个指标。     

Anti-visceral obesity and antioxidant effects of powdered sea buckthorn (Hippophae rhamnoides L.) leaf tea in diet-induced obese mice

The potential health benefits of tea have long been studied. This study examined the role of powdered sea buckthorn leaf tea (SLT) in high-fat diet-induced obese mice. The mice were fed two different doses of SLT (1% and 5%, wt/wt) for six weeks. SLT suppressed body weight gain in a dose-dependent manner and significantly reduced visceral fat, plasma levels of leptin, triglyceride and total cholesterol and ALT activity compared with the high-fat-fed control mice. SLT also decreased hepatic triglyceride and cholesterol concentrations and lipid accumulation, whereas elevated fecal lipid excretion. High-fat feeding resulted in simultaneously decreasing hepatic FAS and G6PD activities and increasing PAP, β-oxidation and CPT activities. However, SLT supplementation during high-fat feeding led to a significant decrease in PAP, β-oxidation and CPT activities with a simultaneous increase in G6PD activity. The hepatic CYP2E1 activity and hepatic and erythrocyte lipid peroxides were significantly lowered with SLT supplements. Hepatic and erythrocyte SOD and CAT activities were also increased with SLT supplements in a dose-dependent manner, whereas GSH-Px activity was increased in erythrocytes only. These results indicate that SLT has potential anti-visceral obesity and antioxidant effects mediated by the regulation of lipid and antioxidant metabolism in high-fat diet-induced obese mice.     

Supplementation of Korean fermented soy paste doenjang reduces visceral fat in overweight subjects with mutant uncoupling protein-1 allele

The purpose of this study was to examine the hypothesis that the antiobesity effect of doenjang, a Korean fermented soy paste is different between the mutant and the wild-type alleles of a polymorphism upstream of the uncoupling protein-1 (UCP-1) gene in overweight subjects. In our randomized, double-blind, placebo-controlled trial, a total of 51 subjects with a body mass index of 23 kg/m² or greater and a waist-to-hip ratio of 0.90 or greater for men or 0.85 or greater for women were randomly assigned to take 9.9 g/d of either a placebo or doenjang for 12 weeks. The relative frequency of the mutant G allele of the UCP-1 polymorphism was 0.60 in the placebo group and 0.62 in the doenjang group. Supplementation of doenjang had no significant effect on the visceral fat area compared with that of the placebo group, but there was a significantly reduced amount of visceral fat in subjects with the G allele of UCP-1 polymorphism. Doenjang supplementation was found to significantly increase the free fatty acid concentration in subjects with both the A allele and the G allele. There was a significant association between visceral fat and age in study subjects with both the wild-type and mutant alleles of the UCP-1 gene. Doenjang supplementation significantly reduced visceral fat and increased the free fatty acid concentrations in subjects with the G allele of the UCP-1 polymorphism, which suggests that doenjang may be related to increased free fatty acid levels caused by elevated lipolysis in these subjects.     

Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus rosuvastatin in hypercholesterolemic patients

ABSTRACT

Objective: To assess the lipid-altering efficacy and safety of ezetimibe/simvastatin single tablet product compared with rosuvastatin at the approved usual starting, next highest, and maximum doses.

Research design and methods: Double-blind, multicenter, 6‐week, parallel-group study in hypercholesterolemic patients (n = 2959). Patients were randomized based on stratification by low-density lipoprotein cholesterol (LDL-C) levels to ezetimibe/simvastatin or rosuvastatin, respectively, at the usual starting (10/20 or 10?mg/day), the next highest (10/40 or 20?mg/day), and maximum doses (10/80 or 40?mg/day).

Results: At all doses and across doses, ezetimibe/simvastatin reduced LDL‐C levels significantly more (52–61%) than rosuvastatin (46–57%; p ≤ 0.001). Significantly greater percentages of all patients (p < 0.001) and high risk patients (p ≤ 0.005) attained LDL‐C levels < 70?mg/dL (1.8?mmol/L) following ezetimibe/simvastatin treatment compared with rosuvastatin at the prespecified doses and across doses. Ezetimibe/simvastatin also produced significantly greater reductions in total cholesterol (?p < 0.001), non-high-density lipoprotein cholesterol (?p < 0.001), lipid ratios (?p ≤ 0.003), and apolipoprotein B (?p < 0.05). Reductions in triglycerides were significantly greater with ezetimibe/simvastatin than rosuvastatin at the usual starting (?p = 0.004) and next highest (?p = 0.006) doses, and across all doses (?p < 0.001). Increases in high-density lipoprotein cholesterol, and decreases in high sensitivity C reactive protein (hsCRP) were similar between treatment groups. Safety profiles were comparable for both treatments; however, the percent of patients with proteinuria was significantly higher following rosuvastatin treatment than ezetimibe/simvastatin, respectively at 10?mg versus 10/20?mg/day (?p = 0.004) and 40?mg versus 10/80?mg/day (?p < 0.001).

Conclusion: Ezetimibe/simvastatin was more effective than rosuvastatin in LDL‐C lowering, and provided greater or comparable improvements in other lipid measures and hsCRP at the approved usual starting, next highest, and maximum doses in hypercholesterolemic patients. Although the doses compared in this study were not equivalent on a milligram basis, the results provide clinically relevant information regarding the use of these drugs for initial therapy and for subsequent use at higher doses when appropriate. Both treatments were generally well-tolerated; however, this study was not powered nor of sufficient duration to assess the prevalence of rare clinical adverse effects. Overall, ezetimibe/simvastatin offers an effective and tolerable treatment option for lipid management. An assessment of its full clinical benefit awaits evaluation in longer-term clinical studies.