他汀类药物对原发性高胆固醇血症患者血管内皮功能的影响

目的　观察辛伐他汀和氟伐他汀对原发性高胆固醇血症患者血管内皮功能的影响。方法　 6 0例原发性高胆固醇血症患者随机分为辛伐他汀组 (5mg/d)或氟伐他汀组 (2 0mg/d) ,每组 30例 ,均治疗 8周 ,2 0例正常对照。采用超声多普勒于治疗前后对其进行血管内皮功能的测定。结果　原发性高胆固醇血症患者肱动脉血流介导的舒张反应较对照组明显减弱 [辛伐他汀组 (3 38±5 48) % ,氟伐他汀组 (1 17± 5 15 ) % ,对照组 (17 5 8± 6 47) % ,P <0 0 0 1],而三组对硝酸甘油的反应差异无显著性 [分别为 (14 6 4± 6 6 8) % ,(14 46± 7 80 ) % ,(18 31± 6 84) % ,P >0 0 5 ]。辛伐他汀或氟伐他汀治疗 8周后均使血清总胆固醇和低密度脂蛋白胆固醇显著降低 ,同时肱动脉内皮依赖性舒张功能较治疗前亦有明显改善 [辛伐他汀组为 (14 6 8± 5 0 5 ) %比 (3 38± 5 48) % ,氟伐他汀组为(13 94± 6 6 8) %比 (1 17± 5 15 ) % ,P值均 <0 0 0 1],而治疗前后肱动脉对硝酸甘油的反应无显著性变化。结论　原发性高胆固醇血症患者血管内皮依赖性舒张功能受损 ,辛伐他汀或氟伐他汀治疗均可显著改善血管内皮依赖性舒张功能 ,二者之间差异无显著性。     

Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia

OBJECTIVES: The purpose of this study was to assess the efficacy and safety of ezetimibe administered with simvastatin in patients with primary hypercholesterolemia. BACKGROUND: Despite the availability of statins, many patients do not achieve lipid targets. Combination therapy with lipid-lowering agents that act via a complementary pathway may allow additional patients to achieve recommended cholesterol goals. METHODS: 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 (LDL-C) > or =145 mg/dl to < or =250 mg/dl and triglycerides (TG) < or =350 mg/dl were randomized to one of the following 10 groups administered daily for 12 consecutive weeks: ezetimibe 10 mg; simvastatin 10, 20, 40, or 80 mg; ezetimibe 10 mg plus simvastatin 10, 20, 40, or 80 mg; or placebo. The primary efficacy variable was percentage reduction from baseline to end point in direct LDL-C for the pooled ezetimibe plus simvastatin groups versus pooled simvastatin groups. RESULTS: Ezetimibe plus simvastatin significantly improved LDL-C (p < 0.01), high-density lipoprotein cholesterol (HDL-C) (p = 0.03), and TG (p < 0.01) compared with simvastatin alone. Ezetimibe plus simvastatin (pooled doses) provided an incremental 13.8% LDL-C reduction, 2.4% HDL-C increase, and 7.5% TG reduction compared with pooled simvastatin alone. Coadministration of ezetimibe and simvastatin provided LDL-C reductions of 44% to 57%, TG reductions of 20% to 28%, and HDL-C increases of 8% to 11%, depending on the simvastatin dose. Ezetimibe 10 mg plus simvastatin 10 mg and simvastatin 80 mg alone each provided a 44% LDL-C reduction. The coadministration of ezetimibe with simvastatin was well tolerated, with a safety profile similar to those of simvastatin and of placebo. CONCLUSIONS: When coadministered with simvastatin, ezetimibe provided significant incremental reductions in LDL-C and TG, as well as increases in HDL-C. Coadministration of ezetimibe with simvastatin was well tolerated and comparable to statin alone.     

辛伐他汀对原发性高胆固醇血症患者血管内皮功能的影响

目的探讨辛伐他汀对原发性高胆固醇血症患者血管内皮功能的影响。方法选择原发性高胆固醇血症患者48例口服辛伐他汀,分别于治疗前、治疗后4周和8周进行血浆内皮素-1（ET-1）、血清一氧化氮（NO）和血脂等指标测定;另选15例健康体检者为对照。结果治疗前高胆固醇血症患者组血浆ET-1显著高于对照组（P<0.05）,而NO显著低于对照组（P<0.01）;辛伐他汀治疗4周后,ET-1、胆固醇、低密度脂蛋白、三酰甘油均显著降低（P<0.01）,NO显著升高（P<0.05）,高密度脂蛋白虽亦升高,但无统计学意义;8周后血浆ET-1继续降低,血清NO继续升高,但两者与健康对照组比较,无统计学意义。结论高胆固醇血症患者存在明显的内皮功能损害;辛伐他汀不仅能够显著降低血脂,而且能够改善血管内皮功能。     

Efficacy and safety of combination simvastatin and colesevelam in patients with primary hypercholesterolemia

PURPOSE: To examine the efficacy and safety of colesevelam hydrochloride, a novel, nonsystemic, lipid-lowering agent, when coadministered with starting doses of simvastatin in a multicenter, randomized, double-blind, placebo-controlled trial. PATIENTS AND METHODS: Subjects with hypercholesterolemia (plasma low density lipoprotein [LDL] cholesterol level > 160 mg/dL and triglyceride level < or = 300 mg/dL) were randomly assigned to receive daily doses of placebo (n = 33), colesevelam 3.8 g (recommended dose, n = 37), simvastatin 10 mg (n = 35), colesevelam 3.8 g with simvastatin 10 mg (n = 34), colesevelam 2.3 g (low dose, n = 36), simvastatin 20 mg (n = 39), or colesevelam 2.3 g with simvastatin 20 mg (n = 37), for 6 weeks. RESULTS: Mean LDL cholesterol levels decreased relative to baseline in the placebo group (P < 0.05) and in all active treatment groups (P < 0.0001). For groups treated with combination therapy, the mean reduction in LDL cholesterol level was 42% (-80 mg/dL; P < 0.0001 compared with baseline), which exceeded the reductions for simvastatin 10 mg (-26%, -48 mg/dL) or 20 mg (-34%, -61 mg/dL) alone, or for colesevelam 2.3 g (-8%, -17 mg/dL) or 3.8 g (-16%, -31 mg/dL) alone (P < 0.001). The effects of combination therapy on serum HDL cholesterol and triglyceride levels were similar to those for simvastatin alone. Side effects were similar among treatment groups, and there were no clinically important changes in laboratory parameters. CONCLUSION: Coadministration of colesevelam and simvastatin was effective and well tolerated, providing additive reductions in LDL cholesterol levels compared with either agent alone.     

Effects of simvastatin on pro-inflammatory cytokines in patients with hypercholesterolemia

BACKGROUND: The role of inflammation in the development of atherosclerosis and its complications has been recently documented. Pro-inflammatory cytokines are among many postulated factors. It is possible that the imbalance between protective cytokines and cytokines affecting endothelial function is one of the underlying mechanisms of myocardial ischaemia. AIM: To examine the effects of simvastatin on IL-2 and TNFalpha levels in patients with hypercholesterolemia. METHODS: The study group consisted of 64 males (age 20-65 years) with hypercholesterolemia. The control group was composed of 10 healthy male volunteers (age 25-40 years) with normal lipid profile. Total cholesterol, LDL-cholesterol, IL-2 and TNFalpha were measured in both groups at baseline, after three months of dietary treatment, and after a further three months of simvastatin therapy. RESULTS: Simvastatin caused a significant decrease in the total and LDL-cholesterol levels compared both with baseline measurements (p=0.0001) and after dietary treatment (p=0.0001). Moreover, simvastatin significantly reduced the IL-2 plasma concentration (p=0.0003). There were no significant differences between IL-2 levels before and following dietary treatment. The TNFalpha serum concentration significantly decreased following the implementation of diet (p=0.0001). Subsequent simvastatin therapy caused further decrease in the TNFalpha serum concentration but this difference did not achieve statistical significance. CONCLUSIONS: A hypolipemic diet significantly decreases TNFalpha serum concentration without affecting the IL-2 level. The subsequent simvastatin therapy significantly reduces IL-2 but not TNFalpha when compared with the post-diet values.     

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.     

辛伐他汀对原发性高胆固醇血症患者内皮依赖性血管舒张功能的影响

目的观察原发性高胆固醇血症患者使用两种剂量辛伐他汀的疗效与安全性及对血管内皮功能的影响。方法60例原发性高胆固醇血症患者随机分为辛伐他汀10mg组(A组,10mg/d)与20mg组(B组,20mg/d),每组30例,均治疗8周,20例正常对照,不予治疗。分别于用药前及疗程结束后查血脂并用超声测定肱动脉内皮功能,同时观察用药安全性。结果(1)原发性高胆固醇血症患者肱动脉内皮依赖性舒张功能较对照组明显减弱(P<0.01)。(2)辛伐他汀10mg与20mg剂量均能有效降低高胆固醇血症患者血清总胆固醇(TC)及低密度脂蛋白胆固醇(LDL C)水平,并显著改善肱动脉内皮依赖性舒张功能,其中20mg剂量组疗效明显优于10mg剂量组。结论原发性高胆固醇血症患者血管内皮依赖性舒张功能受损,两种剂量辛伐他汀均能安全、有效地降低患者血清TC及LDL C并显著改善血管内皮依赖性舒张功能,辛伐他汀20mg剂量组的疗效明显优于10mg剂量组。     

氟伐他汀对高胆固醇血症患者血小板活化功能及胰岛素抵 …

目的：探讨氟伐他汀对高胆固醇血症患者血小板功能及胰岛素抵抗的影响。方法测定３０例高胆固血症或混合性高脂血症患者（治疗组）调脂治疗（氟伐他汀２０ｍｇ／ｄ,治疗４－８周）前后及３０例正常对照者的血脂,α－颗粒膜蛋白ＣＤ６２ｐ（ｃｌｕｓｔｅｒ ｏｆ ｄｉｆｆｅｒｅｎｔｉａｔｉｏｎ６２ｐ,ＣＤ６２ｐ）,血糖及胰岛素水平,并计算胰岛素敏感性指数（ＩＳＩ）。结果（１）治疗组及对照组治疗前的ＣＤ６２ｐ分别为（５     

No effect of bicarbonate treatment on insulin sensitivity and glucose control in non-diabetic older adults

Chronic mild metabolic acidosis is common among older adults, and limited evidence suggests that it may contribute to insulin resistance and type-2 diabetes. This analysis was conducted to determine whether bicarbonate supplementation, an alkalinizing treatment, improves insulin sensitivity or glucose control in non-diabetic older adults. Fasting blood glucose and insulin were measured in stored samples from subjects who had completed a 3-month clinical trial of bicarbonate supplementation to improve indicators of bone and muscle health. One hundred and fifty three ambulatory, non-diabetic adults aged 50 years and older were studied. Subjects were randomized to one of two bicarbonate groups (67.5 mmol/day of potassium bicarbonate or sodium bicarbonate) or to one of two no-bicarbonate groups (67.5 mmol/day of placebo or potassium chloride). Subjects remained on treatment throughout the 3-month study. The primary outcome measures were changes in fasting plasma glucose, serum insulin and HOMA-IR, an index of insulin resistance. Bicarbonate supplementation reduced net acid excretion (adjusted mean±SEM for the change in NAE/creatinine, mmol/mmol, was 0.23±0.22 in the no-bicarbonate group compared with -3.53±0.22 in the bicarbonate group, P<0.001) but had no effect on fasting plasma glucose, serum insulin, or HOMA-IR. In conclusion, bicarbonate supplementation does not appear to improve insulin sensitivity or glucose control in non-diabetic older adults.     

Improved endothelial function with simvastatin but unchanged insulin sensitivity with simvastatin or ezetimibe

In addition to their expected effects on lipid profile, lipid-lowering agents may reduce cardiovascular events because of effects on nonclassic risk factors such as insulin resistance and inflammation. Ezetimibe specifically blocks the absorption of dietary and biliary cholesterol as well as plant sterols. Although it is known that an additional reduction of low-density lipoprotein cholesterol (LDL-C) levels can be induced by the combination of ezetimibe with statins, it is not known if this can enhance some pleiotropic effects, which may be useful in slowing the atherosclerotic process. This study assessed the effects of simvastatin and ezetimibe, in monotherapy or in combination, on markers of endothelial function and insulin sensitivity. Fifty prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia were randomly allocated to 2 groups receiving either ezetimibe (10 mg/d) or simvastatin (20 mg/d) for 12 weeks, after which the drugs were combined for both groups for an additional 12-week period. Clinical and laboratory parameters were measured at baseline and after 12 and 24 weeks of therapy. Homeostasis model assessment of insulin resistance index and the area under the curve of insulin were calculated. As expected, both groups receiving drugs in isolation significantly reduced total cholesterol, LDL-C, apolipoprotein B, and triglyceride levels; and additional reductions were found after the combination period (P < .05). After 12 weeks of monotherapy, plasminogen activator inhibitor-1 levels and urinary albumin excretion were lower in the simvastatin than in the ezetimibe group. No change in homeostasis model assessment of insulin resistance index, area under the curve of insulin, and adiponectin levels was observed after either the monotherapies or the combined therapy. However, simvastatin combined with ezetimibe provoked significant reductions in E-selectin and intravascular cellular adhesion molecule-1 levels that were independent of LDL-C changes. Our findings support claims that simvastatin may be beneficial in preserving endothelial function in prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia. Alternatively, a deleterious effect of ezetimibe on the endothelial function is suggested, considering the increase in intravascular cellular adhesion molecule-1 and E-selectin levels. Simvastatin and ezetimibe, in isolation or in combination, do not interfere with insulin sensitivity.     

Renal function and insulin sensitivity during simvastatin treatment in Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria

Summary The effect of simvastatin (10–20 mg/day) on kidney function, urinary albumin excretion rate and insulin sensitivity was evaluated in 18 Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria and moderate hypercholesterolaemia (total cholesterol ≥5.5 mmol·l⁻¹). In a double-blind, randomized and placebo-controlled design treatment with simvastatin (n=8) for 36 weeks significantly reduced total cholesterol (6.7±0.3 vs 5.1 mmol·l⁻¹ (p<0.01)), LDL-cholesterol (4.4±0.3 vs 2.9±0.2 mmol·l⁻¹ (p<0.001)) and apolipoprotein B (1.05±0.04 vs 0.77±0.02 mmol·l⁻¹ (p<0.01)) levels as compared to placebo (n=10). Both glomerular filtration rate (mean±SEM) (simvastatin: 96.6±8.0 vs 96.0±5.7 ml·min⁻¹·1.73 m⁻², placebo: 97.1±6.7 vs 88.8±6.0 ml·min⁻¹·1.73 m⁻²) (NS) and urinary albumin excretion rate (geometric mean x/÷ antilog SEM) (simvastatin: 18.4x/÷1.3vs 16.2 x/÷1.2 μg·min⁻¹, placebo 33.1 x/÷ 1.3 vs 42.7 x/÷ 1.3 μg·min⁻¹)(NS) were unchanged during the study. A euglycaemic hyperinsulinaemic clamp was performed at baseline and after 18 weeks in seven simvastatin-and nine placebo-treated patients. Isotopically determined basal and insulin-stimulated glucose disposal was similarly reduced before and during therapy in both the simvastatin (2.0±0.1 vs 1.9±0.1 (NS) and 3.1±0.6 vs 3.1±0.7 mg·kg⁻¹·min⁻¹ (NS)) and the placebo group (1.9±0.1 vs 1.8±0.1 (NS) and 4.1±0.6 vs 3.8±0.2 mg·kg⁻¹·min⁻¹ (NS)). No different was observed in glucose storage or glucose and lipid oxidation before and after treatment. Further, the suppression of hepatic glucose production during hyperinsulinaemia was not influenced by simvastatin (−0.7±0.8 vs −0.7±0.5 mg·kg⁻¹·min⁻¹ (NS)). In conclusion, despite marked improvement in the dyslipidaemia simvastatin had no impact on kidney function or urinary albumin excretion rate and did not reduce insulin resistance in these microalbuminuric and moderately hypercholesterolaemic Type 2 diabetic patients.     

Effect of simvastatin on monocyte adhesion molecule expression in patients with hypercholesterolemia

Increased monocyte adherence to the vessel wall is one of the earliest events in atherosclerosis. The mechanism by which hypercholesterolemia causes alterations in endothelial adhesiveness for monocytes is unclear. This study sought to determine if monocyte adhesion molecule expression is affected by low-density lipoprotein (LDL)-cholesterol levels. Patients with hypercholesterolemia and stable coronary artery disease were compared with those without major cardiovascular risk (control). Patients with hypercholesterolemia were treated with simvastatin 20--40 mg/day for 8--10 weeks. Blood samples were examined with flow cytometry assays at baseline and after cholesterol-lowering therapy. Monocyte CD11b and CD14 adhesion molecule expression, measured as fluorescence intensity, were significantly (P<0.0001) higher in hypercholesterolemic patients before the study (176.9+/-9.8 and 138.0+/-4.8, respectively) when compared with that in control subjects (97.2+/-8.1 and 84.0+/-6.4, respectively). Both decreased markedly with treatment: to 118.8+/-6.9 and 103.1+/-3.9, respectively. Monocyte L-selectin expression was significantly lower in patients with hypercholesterolemia before treatment (43.0+/-3.0) when compared with control subjects (79.9+/-2.7), and it increased markedly with treatment (54.2+/-2.5). LDL levels correlated directly with both CD11b and CD14 expression and correlated inversely with L-selectin expression. These data show that hypercholesterolemia affects monocyte adhesion molecule expression which, in turn, decreases with statin-induced plasmatic cholesterol reduction. Such perturbations in monocyte function likely represent a proinflammatory response to hypercholesterolemia and may have a role in the early progression of atherogenesis.     

Effect of simvastatin treatment on the electronegative low-density lipoprotein present in patients with heterozygous familial hypercholesterolemia.

Most described modifications of low-density lipoprotein (LDL) cholesterol share an increase in its negative electric charge; in fact, an electronegative form of LDL can be identified and isolated from plasma. Although the exact nature of the chemical modification of electronegative LDL is still controversial, its toxicity on endothelial cells has been demonstrated. Statins have protective effects against cardiovascular disease that are independent of their lipid-lowering action and which could be due, at least in part, to the prevention of LDL modification. We evaluated the effect of 6 months of simvastatin therapy (40 mg/day) on electronegative LDL proportion and LDL susceptibility to in vitro induced oxidation in 21 patients with heterozygous familial hypercholesterolemia (FH). Eleven normolipemic subjects were analyzed as a control group. Total cholesterol as well as LDL and very low density lipoprotein cholesterol, triglycerides, and apoprotein B decreased 30% after the first month of therapy, with no further decreases thereafter. LDL susceptibility to oxidation was similar in FH patients and controls and did not change throughout the treatment. Electronegative LDL proportion was 35.1 +/- 9.9% in FH patients and 9.1 +/- 2.4% in control subjects (p <0.0001) but, in contrast to total LDL cholesterol and the rest of lipid parameters, it decreased to 28.6 +/- 9.1% in the third month and to 21.2 +/- 7.7% in the sixth month of therapy. The decrease in these cytotoxic particles may be a relevant mechanism by which simvastatin protects against cardiovascular disease.     

Influence of apo E polymorphism on the response to simvastatin treatment in patients with heterozygous familial hypercholesterolemia

In a group of 120 patients with heterozygous familial hypercholesterolemia (FH) the influence of the apolipoprotein E (apoE) polymorphism on pre-treatment plasma lipid levels and on the response to treatment with simvastatin was studied. The apoE phenotype distribution did not differ significantly between the FH group and a sample group of the Dutch population. Differences in pre-treatment lipid levels were not related to the apoE polymorphism in this FH population. After 12 weeks use of a daily dose of 40 mg simvastatin, the plasma total cholesterol, low density lipoprotein (LDL)-cholesterol and plasma triglyceride levels were reduced on average by 33%, 38% and 19%, respectively. At the same time high density lipoprotein (HDL)-cholesterol concentration increased on average by 7%. In the combined FH patient group (males and females) a considerable interindividual variation in response to simvastatin was observed, but was not related to the apoE polymorphism. However, considering males and females separately, we found that female FH patients with the apoE3E3 phenotype responded better on simvastatin treatment with respect to LDL-cholesterol than male FH patients with the apoE3E3 phenotype.     

洛伐他汀治疗冠心病高胆固醇血症对血管内皮功能微循环及胰岛素敏感性的影响

目的　探讨洛伐他汀治疗冠心病高胆固醇血症患者 ,对血管内皮功能、微循环及胰岛素敏感性 (IS)的影响。方法　 4 5例冠心病高胆固醇血症患者 (治疗组 )给予洛伐他汀 (血脂康 )治疗 ,测定治疗前和治疗后 4、8周以及 4 0例正常对照者血脂谱、空腹血糖 (FPG)、空腹胰岛素 (FINS)、一氧化氮 (NO)、内皮素 (ET)、6 -酮 -前列腺素 (6 -Keto -PGF1α)、血栓素B2 (TXB2 )以及甲襞微循环 (NFM )检测并计算总积分值 ,计算IS指数。结果　与对照组比较 ,治疗组治疗前ET、TXB2 、NFM总积分值显著升高 ,NO、6 -Keto -PGF1α、IS指数显著降低。治疗后 4周较治疗前ET、TXB2 、NFM总积分值显著下降 5 3 16± 15 2 3和 6 3 19± 18 72 (P <0 0 1) ,84 13± 2 2 6 7和 94 81± 2 4 6 6 (P <0 0 5 ) ,3 75± 1 0 2和 4 4 6± 1 84 (P <0 0 5 ) ;6 -Keto -PGF1α、NO、IS指数明显升高6 6 89± 18 0 4和 5 4 32± 2 1 73(P <0 0 1) ,5 89± 1 5 4和 5 13± 1 38(P <0 0 5 ) ,- 4 37± 0 34(0 5 2 )和 -4 5 9± 0 4 7(0 4 2 ) (P <0 0 5 ) ;治疗后 8周与治疗前比较TXB2 、NFM总积分值进一步下降P值均 <0 0 1。NO、IS指数进一步升高P值均 <0 0 1,且IS指数的升高与NFM总积分值的下降呈显著负相关关系r =-     

Influence of insulin treatment on insulin sensitivity in insulin requiring type 2 diabetes patients

Insulin resistance in type 2 diabetes subjects was investigated before and 6 months after insulin administration in 43 type 2 diabetes patients (28 females and 15 males). Their age was 56.1+/-8.6 years, diabetes duration 11.7+/-6.8 years, BMI 29.5+/-5.3 kg/m2. All patients were on maximal dosage of oral hypoglycaemic agents and had poor metabolic control (HbA1c 11.2+/-1.6%). Insulin sensitivity was measured by euglycaemic clamp (insulin infusion rate 1 mU kg-1 min-1). The glucose disposal rate (M-value) was considerably lower in patients (2.4+/-1.6 mg kg-1 min-1, 0.2-8.1) compared with healthy subjects (7.1+/-0.2 mg kg-1 min-1, p<0.01). M-value was strongly associated with WHR (r=-0.41, p<0.05). The patients with poorest insulin sensitivity had the highest level of total cholesterol (r=-0.41, p=0.02) and LDL-cholesterol (r=-0.38, p=0.03). After 6 months of insulin treatment BMI was 30.3+/-4.2 kg/m2 (p<0.05), mean weight increase was 2.7+/-0.8 kg. M-value was substantially increased to 4.5+/-2.3 mg kg-1 min-1 (p<0.001), the degree of improvement depended on basal insulin sensitivity (r=-0.55, p<0.01). HbA1c was reduced to 7.7+/-1.4% (p<0.01), the correlation M-value with change of HbA1c (r=-0.59, p<0.01) was shown. Total cholesterol decreased from 6.3+/-1.1 to 5.4+/-1.1 mmol/l, LDL-cholesterol from 4.1+/-1.1 to 3.4+/-1.0 mmol/l, triglycerides from 2.6+/-1.6 to 1.6+/-0.7 mmol/l (p<0.001). In conclusion, insulin treatment of type 2 diabetes patients leads to decrease in insulin resistance due to reduction in glucose toxicity and plasma atherogenicity despite weight gain.     

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.     

Effects of raloxifene and low-dose simvastatin coadministration on plasma lipids in postmenopausal women with primary hypercholesterolemia

Abstract Raloxifene and low-dose simvastatin can each reduce low-density lipoprotein (LDL) cholesterol without affecting high-density lipoprotein (HDL) cholesterol and triglycerides. The objective of this double-blind, 12-week study is to determine whether raloxifene and simvastatin coadministration gives added benefit beyond either monotherapy in affecting fasting lipoproteins and apolipoproteins. Ninety-five postmenopausal women with moderately elevated LDL cholesterol (mean, 146 mg/dL) were randomized to placebo, raloxifene 60 mg/d, simvastatin 10 mg/d, or raloxifene 60 mg/d coadministered with simvastatin 10 mg/d. Raloxifene, simvastatin, and coadministration therapy reduced mean LDL cholesterol by 10.5%, 23.3%, and 31.0% from baseline, respectively ( P < .003 vs baseline; P < .02 vs placebo), and mean apolipoprotein B by 10.4%, 24.2%, and 30.0% from baseline, respectively ( P < .003 vs baseline; P < .02 vs placebo). Each active treatment decreased non-HDL cholesterol compared with placebo ( P < .01). Coadministration treatment was more effective than either monotherapy in reducing LDL cholesterol ( P < .05). Coadministration treatment reduced mean apolipoprotein B ( P < .001) and non-HDL cholesterol ( P < .001) when compared with raloxifene, but was not significantly different when compared with simvastatin. Coadministration therapy increased HDL cholesterol and apolipoprotein A1 levels compared with placebo ( P < .02). No significant effect on triglycerides, very low density lipoprotein cholesterol, and lipoprotein (a) occurred with any active treatment. Raloxifene, simvastatin, and the coadministration therapy were generally well tolerated with clinical adverse effects similar to placebo. No woman had clinically significant elevated liver function tests requiring drug discontinuation. Further data on safety and lipid-lowering effects are needed before raloxifene and statin coadministration may be considered as therapeutic interventions for treating postmenopausal women to achieve National Cholesterol Education Program-Adult Treatment Panel III treatment guidelines.