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1.
HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients   总被引:57,自引:1,他引:56  
Wang PS  Solomon DH  Mogun H  Avorn J 《JAMA》2000,283(24):3211-3216
CONTEXT: Recent animal studies have found that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lipid-lowering drugs (statins) substantially increase bone formation, but whether statin use in humans results in clinically meaningful bone formation or a reduction in the risk of osteoporotic fractures is not known. OBJECTIVE: To determine whether the use of statins is associated with reduced hip fracture risk. DESIGN: Case-control study. SETTING AND PATIENTS: A total of 6110 New Jersey residents aged 65 years or older and enrolled in Medicare and either Medicaid or the Pharmacy Assistance for the Aged and Disabled program. Case patients (n=1222) underwent surgical repair of a hip fracture in 1994. Control patients (n=4888) were identified at a ratio of 4:1 and frequency-matched to case patients for age and sex. MAIN OUTCOME MEASURE: Adjusted odds ratio (OR) of hip fracture by statin use in the 180 days and 3 years prior to the index date (the earliest date of admission for surgery), adjusted for demographic and clinical characteristics and health care utilization. RESULTS: Use of statins in either the prior 180 days (adjusted OR, 0.50; 95% confidence interval [CI], 0.33-0.76) or prior 3 years (adjusted OR, 0.57; 95% CI, 0.40-0.82) was associated with a significant reduction in the risk of hip fracture, even after controlling for variables such as race, insurance status, psychoactive medications, estrogen and thiazide use, ischemic heart disease, cancer, and diabetes mellitus. No significant relationship was observed between use of nonstatin lipid-lowering agents and hip fracture risk. Clear relationships were observed between the degree of reduction in hip fracture risk and the extent of statin use; there was no evidence of such relationships with nonstatin lipid-lowering agents. After adjusting for extent of statin use in the prior 3 years, current use (on the index date) was associated with a 71% reduction in risk (adjusted OR, 0.29; 95% CI, 0.10-0.81). The relationship between statin use and hip fracture risk persisted after controlling for variables such as the number of medications, the Charlson comorbidity index score, and hospitalization or nursing home stay in the last 180 days, as well as after excluding patients who were in a nursing home prior to their index date or who died in the year after their index date. Use of nonstatin lipid-lowering agents was not observed to be associated with reduction in hip fracture risk in any of these alternative models or analyses. CONCLUSIONS: These findings support an association between statin use by elderly patients and reduction in the risk of hip fracture. Controlled trials are needed to exclude the possibility of unmeasured confounders. JAMA. 2000;283:3211-3216  相似文献   

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目的:通过酶联免疫吸附方法(ELISA)检测腹透液中白细胞介素-6(IL-6)、糖类抗原125(CA125)的水平,观察他汀类药物对腹膜透析(PD)患者腹膜纤维化的抑制作用。方法:采用随机对照研究,将50例PD患者随机分为阿托伐他汀(20 mg/d)组和安慰剂组,治疗3个月,停用1个月后,交换处理3个月,留取每次治疗前后腹透液标本及每月留取腹透液标本,观察腹透液中IL-6、CA125的变化情况。结果:阿托伐他汀组治疗后腹透液中IL-6水平较安慰剂组有明显下降,而CA125水平则有明显升高,差异有统计学意义(P<0.05),阿托伐他汀组治疗前后及治疗过程中,CA125呈逐步上升趋势,IL-6水平呈逐步下降趋势,而安慰剂组治疗前后及治疗过程中炎性反应因子变化不明显。结论:阿托伐他汀对腹膜纤维化有一定的拮抗作用。  相似文献   

4.
目的:设计并合成吡咯类HMG-CoA还原酶抑制剂并测定其对HMG-CoA还原酶的抑制活性。方法:根据他汀类药物的构效关系,设计了一类(3R,5R)-7-[2-(4-氟苯基)-3-芳基-4-芳氨甲酰基-5-环丙基-1-吡咯基]-3,5-二羟基庚酸钠化合物(Ia~Im),通过测定烟酰胺腺嘌呤二核苷酸磷酸(NADPH)的降低速率,得到化合物对HMG-CoA还原酶的抑制活性。结果与结论:设计并合成了未见文献报道的HMG-CoA还原酶抑制剂13个,目标化合物结构经IR、1HNMR和HR-ESIMS确证。对所有化合物进行了HMG-CoA还原酶抑制活性测试,有5个化合物有抑制活性,其中化合物Ie的抑制活性与阳性对照药阿托伐他汀相当。  相似文献   

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Policosanol modulates HMG-CoA reductase activity in cultured fibroblasts   总被引:10,自引:0,他引:10  
BACKGROUND: Cholesterol biosynthesis is strictly controlled by 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase. METHODS: Transfer of cultured fibroblasts to a lipid-depleted medium (LDM) up-regulates the enzyme levels. This, in turn, is followed by an accelerated biosynthesis of cholesterol. RESULTS: Exposure of Vero fibroblasts to LDM and policosanol (0.5-50 microg/mL), a new cholesterol-lowering drug purified from sugarcane (Saccharum officinarum L.) wax, decreased in a dose-dependent manner cholesterol biosynthesis from [14C]-acetate and 3H-water, but not from [14C]-mevalonate. CONCLUSIONS: This suggests an effect on HMG-CoA reductase, the rate-controlling enzyme in cholesterol biosynthesis. When enzyme activity was measured in the presence of various concentrations of policosanol (0.5-50 microg/mL), reductase was not suppressed. Therefore, there was no evidence for a competitive or noncompetitive inhibition of enzyme activity. However, after treatment of intact cells with policosanol (50 microg/mL) in the presence of LDM, a suppressive effect on enzyme activity was observed, suggesting a modulatory effect of policosanol on reductase activity. The previous inhibition of enzyme up-regulation by policosanol suggests to date a depression of de novo synthesis of HMG-CoA reductase and/or stimulation of its degradation. However, the exact mechanism by which policosanol inhibits the activity of HMG-CoA reductase still remains unclear. Further studies are needed to clarify the precise mechanism of its inhibitory action on cholesterol biosynthesis.  相似文献   

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To determine the cost-effectiveness of HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors (such as lovastatin) for the primary and secondary prevention of coronary heart disease, we used the Coronary Heart Disease Policy Model, a computer-stimulated model that estimates the risk factor-specific annual incidence of coronary heart disease and the risk of recurrent coronary events in persons with prevalent coronary heart disease. When used for secondary prevention, 20 mg/d of lovastatin was estimated to save lives and save costs in younger men with cholesterol levels above 250 mg/dL (6.47 mmol/L) and to have a favorable cost-effectiveness ratio regardless of the cholesterol level except in young women with cholesterol levels below 250 mg/dL (6.47 mmol/L). Doses of 40 mg/d of lovastatin had favorable incremental cost-effectiveness ratios in men with cholesterol levels above 250 mg/dL (6.47 mmol/L). By comparison, primary prevention had favorable cost-effectiveness ratios only in selected subgroups based on cholesterol levels and other established risk factors. We conclude that current national recommendations regarding medication for secondary prevention are not as aggressive as our projections would suggest, while recommendations regarding the use of medications for primary prevention should consider the cost of medication as well as the risk factor profile of the individual patient.  相似文献   

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氟伐他汀、辛伐他汀治疗肾病时肝功能损害的比较研究   总被引:1,自引:0,他引:1  
徐旭红  刘敏  巴震  吴金土  杨春琴  刘春雅 《浙江医学》2006,28(8):619-621,625
目的 观察两种他汀类药物治疗肾病综合征高脂血症时肝脏功能损害情况。为临床治疗选择较为合适的他汀类药物提供依据。方法 将118例肾病综合征高脂血症患者随机分为3组,3组均行标准剂量激素和一般对症治疗,A组同时使用氟伐他汀。B组同时使用辛伐他汀,C组不用任何降脂药物。观察使用他汀类药物前后各组患者肝功能的变化。结果 A组患者转氨酶变化与对照组比较差异无统计学意义(P〉0.05)。B组转氨酶在用药后短期内升高。与A组、C组及自身用药之前比较,差异具有统计学意义(P〈0.01)。结论 两种他汀类药物治疗肾病综合征高脂血症时,氟伐他汀肝脏功能损害轻于辛伐他汀。可优先选择。  相似文献   

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目的探讨胆固醇合成抑制剂洛伐他汀(10vastatin,LOV)对HL-60细胞HMG-CoA还原酶mRNA表达及细胞增殖功能的影响.方法采用MTT比色法、生长曲线测定、计算细胞生长抑制率、流式细胞仪分析、以及RT-PCR等技术方法,观察LOV对HL-60细胞体外增殖能力、细胞周期分布及HMG-CoA还原酶mRNA表达的影响.结果HL-60细胞经LOV处理后,生长减慢,细胞周期被阻滞在G0/G1期,LOV剂量越大,时间越长,增殖抑制作用越明显;LOV处理HL-60细胞1~3 d,低剂量组(4 lμmol/L)HMG-CoA还原酶mRNA表达上调;而中剂量组(8μnol/L)和高剂量组(16μmol/L)第1天有增加趋势,第2~3天明显降低.结论LOV能显著抑制HL-60细胞增殖,使细胞受阻于G0/G1期,该作用有明显剂量-效应和时间依赖关系;随洛伐他汀处理剂量和时间的不同,HL-60细胞HMG-CoA还原酶mRNA表达表现为上调或下调变化.  相似文献   

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硫氧还蛋白还原酶(thioredoxin reductase,TrxR)是存在于细胞中的含硒同型二聚体黄素酶,其主要功能为调节氧化还原平衡,与细胞的增殖、凋亡以及肿瘤的发生、转移、血管生成中密切相关。含硒C末端活性位点是TrxR的特有结合域,对TrxR与底物的结合具有重要作用,其靶向抑制剂正成为治疗与肿瘤相关疾病的研究热点。本文从TrxR的结构特点及其与肿瘤相关的生理功能出发,根据其与底物结合能力进行分类,将TrxR抑制剂分为可逆和不可逆两类,对两类抑制剂的最新研究进展进行了综述。  相似文献   

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