Effects of ezetimibe coadministered with simvastatin on C-reactive protein in a large cohort of hypercholesterolemic patients

OBJECTIVE: This study assessed the effect of coadministration of ezetimibe and simvastatin on high sensitivity C-reactive protein (hs-CRP) in a large subject cohort (N=1089). METHODS: Data were combined from two nearly identical prospective trials. After dietary stabilization, washout period, and placebo lead-in period, patients with baseline low-density lipoprotein cholesterol (LDL-C) > or =3.75-6.50 mmol/l and triglycerides (TG) < or =4.0 mmol/l were randomized to one of the following daily treatments for 12 weeks: ezetimibe 10 mg; simvastatin monotherapy (10, 20, 40, or 80 mg); ezetimibe 10mg plus simvastatin (10, 20, 40, or 80 mg); or placebo. The primary analysis was the percent change in hs-CRP for the pooled ezetimibe plus simvastatin versus simvastatin monotherapy cohorts. RESULTS: Ezetimibe coadministered with simvastatin more than doubled the hs-CRP reduction compared to simvastatin monotherapy (-33.3% versus -14.3%, p<0.01). At each individual simvastatin dose level, coadministration therapy exerted significant further incremental hs-CRP reductions compared to simvastatin monotherapy. Similar hs-CRP reductions with coadministered ezetimibe and simvastatin were observed in the major subgroups examined (coronary heart disease, gender, age, baseline LDL-C, and body mass index). CONCLUSION: In this large subject cohort, ezetimibe coadministered with simvastatin significantly reduced hs-CRP, suggesting a possible additional anti-inflammatory/anti-atherosclerotic action of combination therapy compared to simvastatin monotherapy.     

辛伐他汀对高脂血症患者血浆C反应蛋白的短期疗效

目的 :了解辛伐他汀对血浆C反应蛋白 (CRP)的影响。方法 :90例高脂血症患者随机分为治疗组4 5例 (口服辛伐他汀 2 0mgqn× 1个月 )和对照组 4 5例 (饮食和生活方式调整 ,未服用调脂药物 ) ,治疗前后分别测定血浆总胆固醇 (TC)、三酰甘油 (TG)、高密度脂蛋白胆固醇 (HDL C)、低密度脂蛋白胆固醇 (LDL C)和高敏感CRP(hsCRP)。结果 :1个月后治疗组TC、LDL C分别降低了 2 0 .8%和 2 1.4 % ,HDL C升高了 6 .3% ,hsCRP降低了 7.6 % ,hsCRP的变化与HDL C的变化呈负相关。对照组上述指标均无明显变化。结论 :辛伐他汀不仅可以调节血脂代谢的失衡 ,而且可以降低血浆CRP水平 ,CRP的降低独立于LDL C的降低 ,但与HDL C的升高相关。     

辛伐他汀对C反应蛋白诱导的单核细胞白细胞介素-6合成的影响

目的　探讨辛伐他汀对C反应蛋白 (C reactiveprotein ,CRP)诱导的人外周血单核细胞白细胞介素 6 (interleu kin 6 ,IL 6 )合成的影响 ,观察辛伐他汀的抗炎作用。方法　密度梯度离心法分离人外周血单核细胞 ,应用酶联免疫吸附测定法观察CRP刺激单核细胞产生IL 6的时间 剂量效应 ,其峰值与辛伐他汀抑制剂组比较。结果　CRP刺激IL 6合成开始的时间是 4h ,呈时间依赖性和剂量依赖性 ,在 2 4h达高峰。辛伐他汀 (10 - 8～ 10 - 6 mol L)呈剂量依赖性抑制单核细胞IL 6合成。结论　辛伐他汀能抑制CRP诱导的单核细胞IL 6合成 ;辛伐他汀对炎症反应的抑制作用提示该药物可用于预防和治疗冠心病。     

Rapid effects of simvastatin on lipid profile and C-reactive protein in patients with hypercholesterolemia

BACKGROUND: Rapid lowering of low-density lipoprotein (LDL) cholesterol levels as well as C-reactive protein (CRP) by administration of drugs may produce early benefit to the coronary endothelium in patients with coronary heart disease and reduce angina and coronary events after revascularization. Limited information has been available in evaluating a potentially effective first 2-week therapeutic approach for the treatment of patients with hypercholesterolemia using a statin. HYPOTHESIS: The study was undertaken to investigate whether a rapid LDL cholesterol and CRP reduction can be achieved by 2-week simvastatin therapy using a common lipid-lowering protocol in patients with hypercholesterolemia. METHODS: Forty-two patients were randomly assigned to 20 or 40 mg/day of simvastatin. Blood samples were drawn at Day 0 and at Day 14 for measuring lipid profile, CRP levels, and hepatic enzymes in all patients. RESULTS: The results showed that both doses of simvastatin (20 and 40 mg) induced significant reductions in total cholesterol (TC, 25 and 38%) and LDL cholesterol (31 and 46%) compared with baseline. However, the highest dose of simvastatin (40 mg) resulted in significantly greater reductions in TC and LDL cholesterol (p = 0.04, p = 0.02, respectively) compared with the group receiving 20 mg (p < 0.04, p < 0.02, respectively). A less significant reduction was observed in mean triglycerides (TG) level (16 and 25%) compared with TC and LDL cholesterol. There was no significant difference in mean high-density lipoprotein (HDL) cholesterol levels compared with baseline in either group. In addition, both doses of simvastatin induced significant reductions in mean CRP levels on Day 14 (22.3 and 23.1%) in a non dose-dependent manner (p < 0.001, respectively. CONCLUSIONS: Our data suggest that a common daily dose of simvastatin, especially 40 mg, is an effective 2-week therapy for patients with hypercholesterolemia, and benefit to the vascular endothelium can be derived quickly by reduction of CRP levels.     

辛伐他汀对高血压病患者血压与C反应蛋白的影响

目的 研究他汀类药物的降脂外效应,对血压及C反应蛋白的影响.方法 随机选择2007-02～2009-02因高血压病住院的患者68例,其中男性46例,女性22例,年龄(66.2±7.6)岁,随机分为两组:治疗组34例,给予培哚普利+苯磺酸氨氯地平联合降压的基础上加用辛伐他汀;对照组34例,使用培哚普利+苯磺酸氨氯地平,治疗4周,观察两组血脂、血压及C反应蛋白变化情况.结果 (1)治疗组总胆固醇、甘油三脂及低密度脂蛋白、胆固醇明显低于对照组;(2)治疗组血压降低幅度明显低于对照组;(3)治疗组C反应蛋白明显低于对照组.结论 辛伐他汀可以降低高血压病患者的血压,同时降低其血清C反应蛋白的水平.     

Efficacy and safety of ezetimibe/simvastatin co- administered with fenofibrate in mixed hyperlipidemic patients with metabolic syndrome

Background: We compared the lipid-altering effects of ezetimibe/simvastatin (EZE/SIMVA) co-administered with fenofibrate (FENO) in mixed hyperlipidemic patients with (MetS) versus those without MetS. Methods: A total of 611 patients, 20 to 79 years old, with LDL-C 130-220 mg/dL (100-180 mg/dL for patients with type 2 diabetes [T2D]), triglycerides (TG) 150-500 mg/dL, and no history of CHD or other CHD risk equivalent disease (except for T2D), were randomized in a 1:3:3:3 ratio into one of the following four treatments for 12 weeks: placebo; EZE/SIMVA 10/20 mg; FENO 160 mg; or EZE/SIMVA+FENO. MetS status was determined in 607 patients using National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Percentage change from baseline in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC), TG, apolipoproteins A-I and B, and C-reactive protein was assessed in these patients with or without MetS. The primary objective was to evaluate the lipid-altering efficacy of EZE/SIMVA+FENO versus FENO monotherapy in the MetS versus non-MetS subgroups. Results: At baseline, patients with MetS had a higher body mass index (BMI) and TG and lower HDL-C. At Week 12, treatment with EZE/SIMVA, FENO, and EZE/SIMVA + FENO led to similar improvements in lipid parameters in patients with MetS compared to those without MetS. Treatment with EZE/SIMVA + FENO and FENO also led to an increase in LDL particle-size pattern after 12 weeks in both subgroups of patients. Conclusions: This post-hoc analysis suggested that co-administration of EZE/SIMVA+FENO had consistent benefits on the lipid profile in mixed hyperlipidemic patients with or without MetS.     

C-reactive protein in patients with familial hypercholesterolemia: no effect of simvastatin therapy

Patients with familial hypercholesterolemia (FH) are especially at risk for premature cardiovascular disease (CVD). Recent studies revealed C-reactive protein (CRP) as a strong predictor of future first or recurrent CVD events, suggesting that CRP plays an important role in the development of atherosclerosis. The aim of this study was to evaluate the effect of one year of simvastatin treatment on serum levels of CRP and to assess the influence of risk factors for CVD on CRP concentrations in patients with FH. We measured baseline CRP levels in 337 patients with FH. A second blood sample, collected after one year of treatment with simvastatin (20--40 mg once daily) was measured in a subgroup of 129 patients. Patients with CVD present at baseline had significantly higher serum levels of CRP (2.26 mg/l versus 1.55 mg/l, P<0.001). CRP levels were associated with smoking, body mass index, age, levels of triglycerides (TG), and the use of NSAIDs or anticoagulation drugs. Simvastatin therapy significantly improved lipid profiles in the intervention group. There was a small, but non-significant decrease of CRP levels upon treatment. CRP decreased from 1.51 mg/l median (interquartile range (IQR) 0.76--3.41) at baseline to 1.24 mg/l median (IQR 0.72--2.92) after treatment, (P=0.328). In conclusion, CRP levels were associated with the presence of CVD in FH patients. Simvastatin therapy had no significant effect on CRP levels in these patients.     

Effect of coadministration of ezetimibe and simvastatin on high-sensitivity C-reactive protein

This study assessed the effect of ezetimibe coadministered with simvastatin on high-sensitivity C-reactive protein (hs-CRP) in patients with primary hypercholesterolemia. After dietary stabilization, a 2- to 12-week washout period, and a 4-week, single-blind, placebo lead-in period, patients with baseline low-density lipoprotein cholesterol ≥145 and ≤250 mg/dl and triglycerides ≤350 mg/dl were randomized to one of these daily treatments for 12 consecutive weeks: ezetimibe 10 mg; simvastatin monotherapy (10, 20, 40, or 80 mg); ezetimibe 10 mg plus simvastatin (10, 20, 40, or 80 mg); or placebo. The primary analysis was the change in hs-CRP for the pooled ezetimibe plus simvastatin versus simvastatin monotherapy groups. Ezetimibe plus simvastatin significantly reduced median hs-CRP levels compared with simvastatin monotherapy (−34.8% vs −18.2%, p< 0.01), and incremental reductions were observed at each simvastatin dose level. Combination therapy-induced significant changes in individual lipid parameters did not explain the observed decreases in hs-CRP. Thus, ezetimibe coadministered with simvastatin resulted in significant incremental decreases in hs-CRP, possibly consistent with an additional anti-inflammatory effect compared with simvastatin monotherapy.     

阿托伐他汀对高脂血症患者补体调节蛋白CD35的影响

目的探讨他汀类调脂药物对高脂血症患者外周血白细胞补体调节蛋白CD35表达的影响及在动脉粥样硬化疾病中的作用。方法选高脂血症患者23例,年龄、性别、体重指数匹配的正常人20例作为对照,用流式细胞术测定外周血白细胞CD35的表达。高脂血症患者使用阿托伐他汀治疗,观察治疗8周后CD35的变化。结果高脂血症患者CD35阳性白细胞、百分率较正常对照组升高(18.40%比12.90%,P<0.05);阿托伐他汀治疗后,CD35阳性白细胞、淋巴细胞、单核细胞、粒细胞平均荧光强度与治疗前比较明显升高(2.02比1.47,3.16比1.60,2.03比1.44,2.05比1.46,P均<0.05),与正常对照组比较亦升高(2.02比1.47,3.16比1.67,2.03比1.52,2.05比1.48,P均<0.05);CD35阳性、淋巴细胞百分率治疗后较治疗前及正常对照组比较均升高(4.93%比3.95%,4.93%比3.35,%,P均<0.05)。结论阿托伐他汀治疗可增加高脂血症患者外周血白细胞补体调节蛋白CD35的表达,提示上调补体调节蛋白的表达可能是他汀类药物延缓动脉粥样硬化进展新的作用机制。     

心血管事件高危患者餐后C反应蛋白质量浓度变化及辛伐他汀干预结果分析

目的 研究心血管事件高危患者高脂餐后血浆C反应蛋白(CRP)质量浓度的变化,探讨极短期辛伐他汀对血浆CRP质量浓度的影响。 方法 对肇庆市端州区人民医院于2003-10～2004-06 70例冠心病及其高危症患者随机分为辛伐他汀组(36例)和常规治疗组(34例),分别在常规治疗的基础上加服辛伐他汀(20mg/d)和安慰剂。治疗前和1周后接受高脂餐负荷试验,检测空腹和餐后4 h血浆CRP质量浓度和血脂水平。 结果 两组患者的餐后血浆甘油三酯和CRP质量浓度较空腹水平明显升高(P<0.05)。1周后常规治疗组的空腹和餐后血浆CRP质量浓度和血脂水平无显著     

高脂血症大鼠肝脏内C-反应蛋白的基因表达

目的研究高脂血症大鼠血清中C-反应蛋白（CRP）、总胆固醇（TC）、甘油三酯（TG）的含量变化和血清CRP水平与肝组织CRP mRNA及蛋白的表达的相关性。方法将体重200g左右SD大鼠随机分成：对照组、高脂血症模型组2组,每组6只,对照组给予普通饮食,高脂血症模型组喂饲高脂饮食。在喂饲6、12w时分别采取各组大鼠的尾静脉血检测血清CRP与TC、TG的含量。12w后采用Realtime-PCR法、Western印迹法检测大鼠肝脏CRP mRNA及蛋白的表达水平。结果在饲养6w时模型组大鼠血清CRP、TC、TG含量明显高于对照组（P〈0.01）;模型组随着建模时间的延长各指标持续增高,12w后显著高于对照组（P〈0.01）;12w后大鼠肝脏CRP mRNA及蛋白表达量,模型组均较对照组明显升高（P〈0.05,P〈0.01）。结论高脂血症大鼠血清中CRP含量升高,其机制与大鼠肝脏CRP mRNA及蛋白表达量升高有关。     

Effect of simvastatin on serum C-reactive protein during hormone replacement therapy

Because statins seem to attenuate the early, increased cardiovascular hazard induced by hormone replacement therapy (HRT), we treated 16 postmenopausal hypercholesterolemic women with coronary artery disease with combined HRT, simvastatin, and the combination of HRT and simvastatin in a double-blind, crossover, placebo-controlled study; we also evaluated C-reactive protein (CRP) levels at the end of each treatment period. We found that only HRT significantly increased CRP compared with placebo, whereas the combination of HRT with simvastatin did not. We concluded that statins may reduce the inflammatory adverse effects associated with the CRP increase induced by HRT.     

辛伐他汀对急性冠状动脉综合征患者早期血浆C-反应蛋白和基质金属蛋白酶-9的影响

目的探讨短期应用辛伐他汀对急性冠状动脉综合征(ACS)患者早期血浆C-反应蛋白(CRP)和基质金属蛋白酶-9(MMP-9)的影响。方法经临床诊断ACS46例,随机分为治疗组和对照组,各23例。对照组给予ACS的一般治疗,不予任何降脂药;治疗组除给予ACS的一般治疗外,加服辛伐他汀40mg/d,共3d。用免疫比浊法和酶联免疫吸附法(ELISA)分别检测2组患者血清CRP和MMP-9。结果2组患者治疗前、后血脂TC、TG、HDL-C、LDL-C的比较差异无统计学意义。2组治疗前和对照组治疗前后的血浆CRP、MMP-9比较差异无统计学意义;治疗组CRP和MMP-9治疗后较治疗前分别下降39.82%和32.39%,均差异有统计学意义(P<0.05)。结论应用辛伐他汀短期治疗ACS患者能够使CRP和MMP-9显著下降,说明他汀类早期应用有抗炎、稳定斑块及防止斑块破裂的作用。     

心电图正常的不稳定型心绞痛及辛伐他汀对C-反应蛋白的影响

目的探讨心电图（ECG）正常的不稳定垂心绞痛（UAP）与ECG有缺血表现的UAP，心绞痛发作时肌钙蛋白I（cTnI）、肌酸磷酸激酶同功酶（CK—MB）、高敏C-反应蛋白（hs—CRP）的变化情况，以及辛伐他汀对hs—CRP、血脂的影响。以提高对冠心病的检出率，减少误诊和漏诊。方法选择经冠脉造影确诊为冠心病而ECG正常的UAP及有ST—T改变的UAP分为两组即：治疗组（24例）和常规治疗组（24例），健康成人（30名）作为对照组。常规治疗组给予UAP的常规治疗，治疗组在常规治疗组的基础上加服辛伐他汀20mg／d，共7d。用免疫荧光法测定治疗前后hs—CRP及血脂的变化。结果常规治疗组、治疗组患者就诊时cTnI、CK—MB、hs—CRP值差异均无统计学意义（P〉O．05），但cTnI、hs—CRP均高于对照组（P〈0．01）。治疗组服用辛伐他订后CRP明显降低（P〈0．01）。结论心电图正常而有典型心绞痛发作的患者不能否定冠心病的诊断，易漏诊、误诊，应引起足够重视。UAP发作早期有微量心肌损伤，尽早给予辛伐他汀可降低CRP，具有抗炎、稳定斑块、减轻动脉粥样硬化的作用。     

不同剂量辛伐他汀早期干预对急性冠状动脉综合征患者血清C反应蛋白的影响

目的观察不同剂量辛伐他汀早期干预对急性冠状动脉综合征(ACS)患者血清高敏C反应蛋白(hs-CRP)水平的影响及调脂作用与安全性。方法75例ACS患者随机分为三组,A组为优化药物治疗,B组为优化药物治疗加辛伐他汀20mg/d,C组为优化药物治疗加辛伐他汀40mg/d,均治疗4周,健康对照组不予治疗。分别于用药前及疗程结束后查hs-CRP及血脂水平,同时观察用药安全性。结果(1)ACS患者hs-CRP、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)含量显著高于健康对照组(P<0.01)。(2)辛伐他汀20mg与40mg治疗4周后,均能显著降低hs-CRP、TC、LDL-C及TG水平(P均<0.01),其中40mg剂量组的疗效明显优于20mg剂量组。结论ACS患者hs-CRP显著升高,存在明显的炎症反应,早期大剂量辛伐他汀调脂干预,能安全更有效地抑制此类炎症反应及脂质过氧化损伤,且呈剂量依赖性。     

Time course of C-reactive protein reduction with simvastatin therapy in patients with type 2 diabetes mellitus

The aim of this study was to investigate the time course of C-reactive protein (CRP) reduction with simvastatin in patients with type 2 diabetes mellitus. Thirty-five subjects (mean +/- SEM body mass index 32.8 +/- 1 kg/m(2), mean +/- SEM glycated hemoglobin 7.3 +/- 0.2%) were studied using a randomized, crossover, double-blind design. Patients were treated with simvastatin 40 mg or placebo for 28 days, with a minimum 28-day intervening washout. On entry, all subjects had low-density lipoprotein cholesterol >100 mg/dl and/or non-high-density lipoprotein cholesterol >130 mg/dl. High-sensitivity CRP (hs-CRP) was measured on days 0, 1, 3, 7, 14, 21, and 28 of each phase; fasting lipids were measured weekly. The mean hs-CRP level was 4.2 +/- 0.6 mg/L at baseline (>3.0 mg/L represents high risk). After simvastatin administration, there was a significant reduction in levels of log(hs-CRP) (p = 0.001). This effect of simvastatin was seen by day 7 (p = 0.008), with maximal reduction seen at day 14 (p = 0.004; hs-CRP in original units 3.1 +/- 0.5 mg/L with simvastatin and 4.1 +/- 0.6 mg/L with placebo). As expected, the change in hs-CRP was not related to low-density lipoprotein cholesterol reduction. By day 28 with simvastatin, hs-CRP had returned to near baseline levels. In conclusion, in patients with type 2 diabetes mellitus, simvastatin reduced hs-CRP within 7 days. However, this potentially beneficial effect was lost within 28 days.     

Effects of gemfibrozil on insulin sensitivity and on haemostatic variables in hypertriglyceridemic patients

In order to assess the efficacy of gemfibrozil on lipid and haemostatic parameters in patients with plurimetabolic syndrome, a multicenter double-blind placebo controlled, parallel study was carried out in 56 patients with primary hypertriglyceridemia and glucose intolerance. These patients had elevated PAI activity and antigen and t-PA antigen levels at rest and after venous occlusion. Gemfibrozil reduced plasma triglyceride levels (P<0.001), whereas it increased free fatty acids (P<0.05) and high density lipoprotein cholesterol levels (P<0.05). In those patients reaching normalization of plasma triglyceride levels (triglyceride reduction > or =50%) (n=15), insulin levels (P<0.05) as well as the insulin resistance index were reduced by gemfibrozil treatment, suggesting an improvement of the insulin resistance index in this patient subgroup. Gemfibrozil treatment did not affect plasma fibrinolysis or fibrinogen levels, despite marked reduction of plasma triglycerides and improvement of the insulin sensitivity associated with triglyceride normalization.