Atorvastatin in the treatment of patients with hereditary hypercholesterolemia

Efficacy and tolerability of atorvastatin (20 mg/day) were assessed in a 3 month study on 19 patients (5 men, 14 women, mean age 52.3 years) with familial hypercholesterolemia. Average baseline levels of total cholesterol (CH) and low density lipoprotein (LDL) CH were 10.7 and 8.6 mmol/l, respectively. By the end of 3 months levels of CH, LDL CH, triglycerides and atherogeneity index decreased by 32, 41, 16 and 45%, respectively. This was accompanied by 21% increase of high density lipoprotein CH level. There were no cases of AST or ALT activity elevation above 3 upper limits of normal values. However 1 patient had asymptomatic elevation of ALT activity up to 53 U/l which did not cause interruption of therapy. Creatine kinase remained normal throughout the study period. Three patients (16%) stopped taking atorvastatin because of side effects. Thus in patients with familial hypercholesterolemia the dose of atorvastatin 20 mg/day was sufficiently well tolerated and provided effective control of lipid levels.     

Time course differences for statin-induced pleiotropic effects in hypercholesterolemic patients

BACKGROUND: It is unclear whether there are temporal differences for the pleiotropic effects for different members of the statin class. The present study investigated differences in the short- and intermediate-term pleiotropic effects of statins in hypercholesterolemic patients. METHODS: Thirty-five hypercholesterolemic patients were randomly treated with either atorvastatin or cerivastatin for 3 months. We measured fasting lipid concentrations, thiobarbituric acid reactive substances (TBARS), fibrinolytic parameters, and flow-mediated dilation of the brachial artery (FMD) at baseline and after 2 weeks and 3 months of therapy. RESULTS: After 2 weeks of therapy, atorvastatin decreased the low density lipoprotein (LDL) cholesterol, small, dense LDL cholesterol (34+/-22 vs. 18+/-20%, P<0.01), remnant-like particles (RLP) cholesterol (8.8+/-6.0 vs. 5.1+/-2.6 mg/ml, P<0.01), and TBARS (3.3+/-1.0 vs. 3.1+/-0.9 nmol/ml, P<0.05), and cerivastatin decreased LDL cholesterol. After 3 months of therapy, atorvastatin decreased small dense LDL cholesterol (8+/-13%, P<0.0001) additionally, and cerivastatin decreased small, dense LDL cholesterol (51+/-11 vs. 12+/-22%, P<0.0001) and plasminogen activator inhibitor type 1 (68+/-32 vs. 51+/-21 ng/ml, P<0.05). FMD increased significantly in both groups after 2 weeks, although the relative change in FMD was greater with cerivastatin therapy after 2 weeks than atorvastatin therapy (60+/-78 vs. 23+/-26%, P<0.05). However, FMD was the same for both groups after 3 months (58+/-65 vs. 66+/-61%, NS), because atorvastatin additionally increased FMD. There was no correlation between these pleiotropic effects and the improvement in the lipid profile for either group. CONCLUSIONS: These findings suggest that the degree of pleiotropic effect as well as the time course for the effect are different among members of the statin class of drugs.     

Atorvastatin but not L-arginine improves endothelial function in type I diabetes mellitus: a double-blind study

OBJECTIVES: We sought to determine the effects of oral L-arginine and the hexamethylglutaryl coenzyme A reductase inhibitor atorvastatin on endothelial function in young patients with type I diabetes mellitus (DM). BACKGROUND: Endothelial dysfunction, a key early event in atherosclerosis, occurs in young patients with type I DM, and its reversal may benefit the progression of vascular disease. Cholesterol reduction in L-arginine improve endothelial function in nondiabetic subjects, but their effect in patients with type I DM is unknown. METHODS: In a double-blind, 2x2 factorial study, we investigated the effect of L-arginine (7 g twice daily) and atorvastatin (40 mg/day) on conduit artery vascular function in 84 normocholesterolemic young adults (mean+/-SD: age 34 years [range 18 to 46], low density lipoprotein [LDL] cholesterol 2.96+/-0.89 mmol/liter) with type I DM. Brachial artery dilation to flow (flow-mediated dilation [FMD]) and to the direct smooth muscle dilator glyceryl trinitrate (GTN) were assessed noninvasively using high resolution ultrasound at baseline and after six weeks of treatment. RESULTS: Atorvastatin resulted in a 48+/-10% decrease in serum LDL cholesterol levels, whereas L-arginine levels increased by 247+/-141% after L-arginine therapy. By analysis of covariance, treatment with atorvastatin resulted in a significant increase in FMD (p = 0.018. L-Arginine therapy had no significant effect on endothelial function, and there was no significant change in dilation to GTN after either intervention. CONCLUSIONS: In young patients with type I DM, improvement in endothelial dysfunction can be demonstrated after just six weeks of treatment with atorvastatin. In contrast to studies of hypercholesterolemia, however, L-arginine had no benefit. Treatment with atorvastatin at an early stage may have an impact on the progression of atherosclerosis in these high risk patients.     

Sustained long-term improvement of arterial endothelial function in heterozygous familial hypercholesterolemia patients treated with simvastatin

Patients with heterozygous familial hypercholesterolemia (hFH) are at very high risk for premature coronary heart disease. In the last decade, treatment with statins has reduced cardiovascular mortality in these patients. The aim of this study was to analyze arterial endothelial function assessed as flow-mediated dilatation (FMD) and soluble E-selectin (sE-selectin) levels in patients with hFH under a long-term lipid-lowering treatment. Twenty-five patients who completed the study received a dose of simvastatin to achieve a treatment goal of at least 30% reduction in serum low-density lipoprotein (LDL)-cholesterol (LDL-C) for 52 weeks. Functional and biochemical measurements were taken at entry, and at week 12 and 52 of treatment. FMD was measured by vascular ultrasound of the brachial artery. sE-selectin, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 were determined by enzyme linked immunosorbent assay (ELISA). LDL-C levels were significantly reduced by treatment at week 12 and maintained at week 52 (reduction vs. baseline, 44+/-12 and 43+/-11%, respectively, P<0.0001). A significant improvement in endothelial function, measured as FMD (baseline, 4.7+/-6.2%; 12 weeks, 12.3+/-5.9%; 52 weeks, 9.7+/-4.7%; P<0.005) and a reduction in sE-selectin levels (baseline, 16.2+/-3.4 ng/ml; 12 weeks, 11.0+/-3.2 ng/ml; 52 weeks, 12.3+/-4.2 ng/ml; P<0.01) were observed. Endothelial-independent relaxation induced by nitroglycerin was not modified during the study. Our results indicate that a long-term treatment with simvastatin produced a sustained beneficial effect in endothelial function in hFH patients.     

Early effects on endothelial function of atorvastatin 40 mg twice daily and its withdrawal

Combined hyperlipidemia is associated with endothelial dysfunction. Atorvastatin has lipid-lowering and pleiotropic properties, including a protective effect on endothelial function. This study investigated the short- and medium-term effects of therapy with atorvastatin and of its discontinuation on lipid lowering and endothelial function. In 33 patients with combined hyperlipidemia who had been randomized and treated for 6 weeks with 40 mg of atorvastatin twice daily (n = 23) or placebo (n = 10), fasting lipid levels and flow-mediated dilation (FMD) of the brachial artery were measured at baseline, after 12 hours, 1 week, and 6 weeks during therapy, and 36 hours after discontinuation of therapy. Thereafter, all patients received 20 mg/day of atorvastatin for another 6 weeks. In the atorvastatin group, low-density lipoprotein cholesterol was decreased by 30% and 46% after 1 and 6 weeks, respectively (p <0.0001 for the 2 comparisons). In patients who already showed an impaired FMD at the beginning of the study (n = 15), atorvastatin caused a significant improvement in FMD, from 2.6% at baseline to 4.0% and 6.3% after 1 and 6 weeks, respectively (p <0.05 and <0.001). Thirty-six hours after withdrawal of atorvastatin, the FMD in this group decreased again to 2.8% (p <0.05), whereas low-density lipoprotein cholesterol level remained unchanged. The 6 patients with normal FMD at baseline showed no improvement in FMD during therapy or any decrease after withdrawal of the drug. In conclusion, only patients with endothelial dysfunction profit from high-dose atorvastatin treatment. When the treatment is abruptly discontinued, the effect on FMD disappears in 36 hours.     

阿托伐他汀对冠心病患者的血管舒张功能的影响

目的观察阿托伐他汀对冠心病患者血管舒张功能的作用。方法将入选60例冠心病并高胆固醇血症患者随机分为阿托伐他汀治疗组(A组)和对照组(B组)。分别测定血清胆固醇、三酰甘油、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇。并应用高分辨率超声技术,检测治疗前、后两组肱动脉血流介导和硝酸甘油介导的舒张功能。结果治疗前,冠心病并高胆固醇血症患者肱动脉血流介导和硝酸甘油介导的舒张功能均低于健康对照组(P<0.01)。经阿托伐他汀治疗6个月后A组血浆总胆固醇、三酰甘油和低密度脂蛋白胆固醇显著降低(P<0.01),高密度脂蛋白胆固醇显著升高(P<0.01)。随着血脂的改善,肱动脉内皮依赖性血管舒张功能显著提高(P<0.01),但硝酸甘油介导的血管舒张功能未见改善(P>0.05)。结论冠心病并高胆固醇血症患者存在内皮依赖性血管舒张功能障碍,经阿托伐他汀调脂治疗后,受损的内皮依赖性血管舒张功能得到明显改善。     

Effects of atorvastatin therapy on the low-density lipoprotein subfraction, remnant-like particles cholesterol, and oxidized low-density lipoprotein within 2 weeks in hypercholesterolemic patients.

The short- and intermediate-term pleiotropic effects of atorvastatin were investigated in 18 hypercholesterolemic patients, as well as the temporal differences in these pleiotropic effects. Atorvastatin was given for 3 months and fasting lipid concentrations, thiobarbituric acid reactive substances (TBARS), fibrinolytic parameters, and flow-mediated dilation of the brachial artery (FMD) were measured at baseline and after 2 weeks and 3 months of therapy. Atorvastatin reduced the total cholesterol (273+/-34 vs 188+/-31 mg/dl, p<0.0001), low-density lipoprotein-cholesterol (LDL-C: 174+/-28 vs 111+/-23 mg/dl, p<0.0001), small, dense LDL-C (34+/-22 vs 18+/-20%, p<0.01), remnant-like particles cholesterol (RLP-C: 8.8+/-6.0 vs 5.1+/-2.6 mg/ml, p<0.01), and TBARS (3.3+/-1.0 vs 3.1+/-0.9 nmol/ml, p<0.05) after 2 weeks. Atorvastatin decreased the concentration of small, dense LDL-C again after 3 months (8+/-13%, p<0.0001). The plasma concentrations of the fibrinolytic parameters did not change significantly after 3 months of atorvastatin therapy. FMD increased significantly after 2 weeks (5.6+/-2.1 vs 6.3+/-2.0%, p<0.01) and additionally increased after 3 months of therapy (8.3+/-1.9%, p<0.0001). There were no correlations between the pleiotropic effects and the improvement in the lipid profile. The results indicate some short-term pleiotropic effects of atorvastatin therapy within 2 weeks, which may be important with respect to the early benefits of statin therapy.     

早期阿托伐他汀联合普罗布考治疗对急性冠状动脉综合征患者血管内皮功能的影响

目的 观察阿托伐他汀联合普罗布考早期治疗对急性冠状动脉综合征(ACS)患者血管内皮功能的影响.方法 30例ACS患者在入院24 h内随机分到他汀组(阿托伐他汀20 mg/d,n=15)与联合治疗组(阿托伐他汀20 mg/d和普罗布考500 mg/d,n=15).治疗前、治疗1周和4周后分别检测患者血清血脂与高敏C反应蛋白(hs-CRP)水平,并应用高频超声测肱动脉血流介导的内皮依赖血管舒张功能(FMD)和由硝酸甘油诱导的内皮非依赖血管舒张功能(NMD).结果 经治疗1和4周后,两组血清总胆固醇、低密度脂蛋白胆固醇(LDL-C)和hs-CRP水平均低于治疗前,联合治疗组血清总胆蚓醇水平下降较他汀组更明显(P<0.05).治疗1周后,FMD均明显高于治疗前(他汀组:3.75%±0.78%比1.09%±0.44%;联合治疗组:3.67%±0.36%比1.24%±0.37%;均P<0.01),两组比较差异无统计学意义.联合治疗组4周后FMD明显高于1周后(6.85%±0.64%比3.67%±0.36%,P<0.01);他汀组则无显著变化(P=0.954).两组NMD在治疗4周后均明显高于治疗前(P<0.01),但两组比较差异无统计学意义.相关分析显示,FMD和NMD的改善与血脂或hs-CRP水平的变化无显著相关.结论 提示早期阿托伐他汀联合普罗布考治疗较单用阿托伐他汀能更明显地改善ACS患者的血管内皮功能.     

The influence of low-dose atorvastatin on lipid levels and endothelial vascular function in patients with significant coronary artery stenosis

BACKGROUND: Hyperlipidaemia is a well-established risk factor of the progression of coronary artery disease (CAD). Statins such as atorvastatin, as lipid-lowering agents, can not only normalise serum lipid levels, but also may improve endothelial function, reduce vascular inflammation and enhance plaque stability. AIM: To evaluate the efficacy of a low-dose atorvastatin regimen (10 mg daily) in patients with CAD. METHODS: Seventy-nine patients with stable angina of II or III functional class and angiographically significant stenosis of coronary arteries (>70%) entered a 12-week treatment period with atorvastatin 10 mg/day. Lipid profile, which included total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were assessed at baseline and after treatment at week 12. In addition, flow-mediated vasodilatation (FMD) and nitrate-induced dilation (NID) of the brachial artery were measured before and after treatment. RESULTS: Among 79 patients included in the study, in 54 (68%) the target TC value <5.0 mmol/l, and in 51 (65%) the LDL-C level <3.0 mmol/l were achieved. Atorvastatin decreased TC level by 31% (p<0.01), LDL-C level by 35% (p<0.01), TG level by 23% (p<0.01) and increased HDL-C level by 8% (p<0.01). FMD was increased by 61 % (p<0.01) and normalised in 88% of patients after 3-month therapy of atorvastatin. NID was increased by 16% (p<0.05). CONCLUSION: Low-dose treatment with atorvastatin (10 mg daily) is effective in reducing blood lipids and is associated with the improvement of endothelial function in patients with CAD.     

Effect of therapy with rosuvastatin on lipid spectrum, factors of inflammation and endothelial function in patients with ischemic heart disease

Rosuvastatin (10 mg) was given for 3 months to 30 men (mean age 57+/-9 years) with total cholesterol (CH) above 5.2 mmol/l. Questioning, physical examination, registration of ECG, measurement of levels of total, low density lipoprotein (LDL), high density lipoprotein (HDL) CH, and triglycerides (TG), assessment of endothelium-dependent brachial artery dilation were carried out at baseline and in 3 months. It was noted that 3 months therapy with rosuvastatin exerted positive effect on blood lipid spectrum: lowering of concentration of total CH (-31%, baseline 6.52+/-0.92, after therapy 4.47+/-0.96 mmol/l, p<0.0001), TG (-39%, baseline 2.73+/-1.56, after therapy 1.67+/-0.71 mmol/l, p<0.001), LDLCH (-44%, baseline 4.11+/-0.85, after therapy 2.40+/-0.90 mmol/l, p<0.0001), elevation of HDLCH (+6%, baseline 1.15+/-0.27, after therapy 1.22+/-0.34 mmol/l, p=0.08). Target LDL CH level (<2.6 mmol/l) was achieved in 23 patients (77%). Significant lowering of concentration of C-reactive protein (CRP) (-56%) and interleukin 6 (-25%) was also established. Before beginning of therapy mean flow dependent dilation was 6.1+/-1.64%, after therapy -- 10.4+/-5.0% (p<0.05). Treatment of men with ischemic heart disease with rosuvastatin (10 mg for 3 months) led to achievement of target values of LDLCH in 77% of them, to significant lowering of concentrations of CRP and interleukin 6, and to improvement of endothelial function.     

Low serum bilirubin levels are independently and inversely related to impaired flow-mediated vasodilation and increased carotid intima-media thickness in both men and women

BACKGROUND: Elevated levels of low-density lipoprotein (LDL) cholesterol and its oxidative modification have been described to be involved in the process of atherogenesis. Bilirubin, an antioxidant, prevents oxidative modification of LDL and therefore may protect from atherosclerosis and coronary heart disease (CHD). Impaired brachial artery flow-mediated dilatation (FMD), which means endothelial dysfunction (ED) and carotid intima-media thickness (IMT) are predictors for the development and progression of atherosclerosis. In the present study, FMD and IMT were studied in healthy subjects with lower and higher serum bilirubin concentrations in physiological ranges. METHODS: Ninety-one healthy subjects between 25 and 45 years of age (47 with lower and 44 with higher serum bilirubin concentrations) were included in this study. Carotid IMT and brachial artery flow-mediated dilatation was measured by means of high-resolution vascular ultrasound. FMD was assessed by establishing reactive hyperemia and endothelium-independent dilatation (EID) was determined by using sublingual isosorbide dinitrate. RESULTS: EDD in subjects with lower serum bilirubin concentrations was significantly worse than in those with higher serum bilirubin concentrations (11.6+/-4.4% versus 7.2+/-4.7%, respectively, p<0.0001). EID measurements were not significantly different between the groups (16+/-5.1% versus 16.8+/-7%, respectively). In addition, carotid IMT was significantly greater in subjects with lower serum bilirubin concentrations (0.5+/-0.13 mm versus 0.42+/-0.07 mm, p<0.0001). Furthermore, FMD in women with lower serum bilirubin concentrations was significantly lower than in women with higher serum bilirubin concentrations (11.5+/-4.9% and 17.5+/-4.7%, respectively, p<0.001). Accordingly, men with lower serum bilirubin concentrations had significantly lower FMD as compared to hyperbilirubinemic ones (11.7+/-3.6% versus 16.7+/-4.8%, respectively, p=0.009). Conversely, carotid IMT was significantly greater in both women and men with lower serum bilirubin concentrations compared to the subjects with elevated serum bilirubin concentrations (0.51+/-0.08 versus 0.41+/-0.08, p<0.001; 0.55+/-0.12 versus 0.40+/-0.07, p=0.002, in women and men, respectively). CONCLUSION: The healthy subjects with lower serum bilirubin concentrations show significant ED and increased carotid IMT, which are predictors for atherosclerosis.     

Early statin therapy restores endothelial function in children with familial hypercholesterolemia

OBJECTIVES: This study was designed to determine whether simvastatin improves endothelial function in children with familial hypercholesterolemia (FH). BACKGROUND: Endothelial function measured by flow-mediated dilation of the brachial artery (FMD) is used as a surrogate marker of cardiovascular disease (CVD). Adult studies have shown that statins reverse endothelial dysfunction and therefore reduce the risk for future CVD. METHODS: The study included 50 children with FH (9 to 18 years) and 19 healthy, non-FH controls. Children with FH were randomized to receive simvastatin or placebo for 28 weeks. The FMD was performed at baseline and at 28 weeks of treatment. RESULTS: At baseline, FMD was impaired in children with FH versus non-FH controls (p < 0.024). In the simvastatin FH group, FMD improved significantly, whereas the FMD remained unaltered in the placebo FH group throughout the study period (absolute increase 3.9% +/- 4.3% vs. 1.2% +/- 3.9%, p < 0.05). In the simvastatin FH group, FMD increased to a level similar to the non-FH controls (15.6% +/- 6.8% vs. 15.5% +/- 5.4%, p = 0.958). Upon treatment, the simvastatin FH group showed significant absolute reductions of total cholesterol (TC) (-2.16 +/- 1.04 mmol/l, 30.1%) and low-density lipoprotein cholesterol (LDL-C) (-2.13 +/- 0.99 mmol/l, 39.8%). The absolute change of FMD after 28 weeks of therapy was inversely correlated to changes of TC (r = -0.31, p < 0.05) and LDL-C (r = -0.31, p < 0.05). CONCLUSIONS: Our data show significant improvement of endothelial dysfunction towards normal levels after short-term simvastatin therapy in children with FH. These results emphasize the relevance of statin therapy in patients with FH at an early stage, when the atherosclerotic process is still reversible.     

Comparison of rosuvastatin versus atorvastatin in patients with heterozygous familial hypercholesterolemia

Heterozygous familial hypercholesterolemia (HFH) is a common genetic disorder that confers a significantly increased risk of early coronary artery disease. This study compared atorvastatin and rosuvastatin in reducing low-density lipoprotein (LDL) cholesterol in HFH in a global, 18-week, weighted-randomization, double-blind, parallel-group, forced-titration study. Following a 6-week diet lead-in, 623 patients were randomized to 20 mg/day of atorvastatin (n = 187) or rosuvastatin (n = 436) with forced titration at 6-week intervals to 80 mg/day. The primary end point was percentage change in LDL cholesterol from baseline to week 18. At week 18, rosuvastatin therapy produced a significantly greater reduction in LDL cholesterol than atorvastatin (-57.9% vs -50.4%; p <0.001) and a significantly greater increase in high-density lipoprotein (HDL) cholesterol (12.4% vs 2.9%; p <0.001). Rosuvastatin also produced significantly greater reductions in apolipoprotein-B and all 4 major lipid ratios, as well as a significantly greater increases in apolipoprotein A-I (all p <0.001). More patients with HFH with coronary artery disease achieved the National Cholesterol Education Program Adult Treatment Panel III goal of LDL cholesterol <100 mg/dl (<2.6 mmol/L) on rosuvastatin 40 and 80 mg than atorvastatin 80 mg (17%, 24%, and 4.5%, respectively). High-sensitivity C-reactive protein median values were reduced by 33% to 34% in both the 80-mg rosuvastatin- and atorvastatin-treated groups. Both treatments were well tolerated. Thus, in HFH, rosuvastatin force titrated from 20 to 80 mg/day produced significantly greater reductions than atorvastatin 20 to 80 mg/day in LDL cholesterol and improvements in HDL cholesterol and other lipid parameters, and enabled more patients to achieve LDL cholesterol goals.     

Atorvastatin increases low-density lipoprotein size and enhances high-density lipoprotein cholesterol concentration in male, but not in female patients with familial hypercholesterolemia.

The effects of atorvastatin (Lipitor) were evaluated in 40 patients with familial hypercholesterolemia (FH). Following a 6 week drug-free baseline period 20 male and 20 female patients were treated with atorvastatin 40 mg once daily (QD) for the initial 6 weeks increasing to 80 mg QD during the following 6 weeks. Atorvastatin 40 and 80 mg resulted in a dose related reduction in LDL cholesterol of 44 and 50% (P<0.001), respectively. The reduction of triglycerides (TG) was 35% (P<0.001) with 40 and 80 mg atorvastatin. The lipoprotein lipase and the hepatic lipase activity decreased dose independently by 13% (P<0.05) and 18% (P<0.01), respectively. In males, a dose independent increase in high-density lipoprotein (HDL) cholesterol concentration was observed of 8%, (P<0.05). In females, the HDL cholesterol concentration did not change. Baseline LDL size in the females was significantly larger than in the males, being 268+/-6 A and 264+/-8 A (P<0.05), respectively. In males LDL size increased significantly from 264+/-8 A at baseline to269+/-6 A at 40 mg (P<0.05) and to 270+/-5 A (P<0.05) at 80 mg atorvastatin. In females LDL size did not change upon treatment with atorvastatin 40 and 80 mg QD. In conclusion, atorvastatin has the ability to decrease cholesterol and triglyceride concentrations as well as the activity of both lipoprotein and hepatic lipase activity. Additionally it has a favorable effect on LDL size and HDL cholesterol concentration in male, but not in female FH patients.     

Simvastatin (40 mg/day) in patients with hereditary hypercholesterolemia: effect on high density lipoprotein cholesterol

AIM: To study effect of simvastatin of the level of high density lipoprotein (HDL) cholesterol (CH). MATERIAL AND METHODS: Simvastatin (40 mg/day) was given for 3 months to 15 patients (3 men, 12 women, mean age 56-/+10.3 years) with hereditary type II hypercholesterolemia after washout from lipid lowering therapy. Initial level of HDL CH was below and above 1.0 mmol/l in 7 and 8 patients, respectively. Blood lipids, activity of liver enzymes and creatine kinase were determined after 1 and 3 months of therapy with simvastatin. Safety and tolerability of simvastatin were also studied. RESULTS: Simvastatin was well tolerated. In 1 patient the drug was stopped because of pain in the liver and nausea. In patients with initially low HDL CH levels of total and low density lipoprotein (LDL) CH significantly decreased by 29.6 and 36.8%, respectively, after 3 months, while level of HDL CH increased by 20% after 1 month of therapy. In patients with initially normal HDL CH levels of total and LDL CH significantly decreased by 31.1 and 32.6%, respectively, while those of triglycerides and HDL CH did not change. CONCLUSION: In patients with hereditary hypercholesterolemia 40 mg/day of simvastatin besides pronounced lowering of LDL CH level caused significant increase of HDL CH (up to 20% in 1 month) in patients with initially low level of this parameter.     

Lack of significant effects of methionine loading on endothelial function in elderly volunteers

OBJECTIVE: To test the hypothesis that an acute increase in plasma homocysteine concentration (Hcy) produced by methionine loading is associated with an acute decrease in brachial artery blood flow measured by flow-mediated dilatation (FMD) using forearm plesthysmography. DESIGN: A double-blind, cross-over, placebo controlled design was used and FMD of the brachial artery, plasma Hcy, plasma methionine, total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, plasma triglyceride, oxidised LDL, apolipoproteins (Apo) A1 and B and C reactive protein (CRP) were measured between 12 and 20 hours after methionine loading or placebo. RESULTS: Between 12 and 20 hours, after a methionine loading test, acute hyperhomocysteinaemia had no significant effect on mean FMD compared to placebo (57.08+/-6.18ml/100ml/min versus 63.46+/-5.87ml/100ml/min, p<0.5). The mean age of the eight subjects was 71.5+/-6.9 years. Twelve hours after methionine, mean triglyceride concentration was significantly increased by 23.0% compared to placebo (1.51+/-0.47mmol/l versus 1.23+/-0.44mmol/l, p<0.02). CONCLUSION: In elderly volunteers, acute hyperhomocysteinaemia induced by methionine loading resulted in no significant late impairment of endothelial function although further investigation is recommended. Acute hyperhomocysteinaemia resulted in a significant increase in plasma triglyceride concentration.     

Comparison of the efficacy and tolerability of simvastatin and atorvastatin in the treatment of hypercholesterolemia

BACKGROUND: Simvastatin and atorvastatin are effective statins for treating hypercholesterolemia. HYPOTHESIS: The study was undertaken to compare the efficacy and tolerability of simvastatin 20 and 40 mg/day and atorvastatin 10 and 20 mg/day. METHODS: In this multinational, open-label, crossover study, 258 patients with primary hypercholesterolemia were randomized after 4 weeks of diet plus placebo to once-daily administration of a starting dose sequence of simvastatin (20 mg) or atorvastatin (10 mg), or a higher dose sequence of simvastatin (40 mg) or atorvastatin (20 mg) for 6 weeks. Patients were then switched after a 1-week washout to the corresponding starting or higher dose of the alternate drug for a second 6-week period. The primary endpoint was the mean percent change from baseline to Week 6 in low-density lipoprotein (LDL) cholesterol; percent changes from baseline in total cholesterol, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B were also compared. Safety was assessed through adverse experiences and laboratory measurements. RESULTS: Both statins produced statistically significant improvements in all measured plasma lipids and lipoproteins. The main treatment comparison showed no statistically significant difference in changes in LDL cholesterol and triglycerides, whereby the overall effects were comparable when doses of 20 mg and 40 mg of simvastatin were compared with atorvastatin 10 mg and 20 mg. The mean percent reductions for LDL cholesterol from baseline to Week 6 ranged from 35-42% for the entire study cohort. An LDL cholesterol level < or = 130 mg/dl (3.4 mmol/l) was achieved in approximately 70% of patients treated with both drugs in this study. Simvastatin and atorvastatin were well tolerated at the doses studied. CONCLUSION: In patients with hypercholesterolemia, the most commonly used doses of simvastatin and atorvastatin produced similar changes in LDL cholesterol and achieved an LDL cholesterol level < or = 130 mg/dl (3.4 mmol/l) in a similar number of patients. Both statins were well tolerated.     

The Role of Low Density Lipoprotein Apheresis in the Treatment of Familial Hypercholesterolemia

Abstract: The chief indication for low density lipoprotein (LDL) apheresis is the treatment of homozygous familial hypercholesterolemia (FH), a potentially fatal condition that responds poorly to conventional therapy. Dextran sulfate/cellulose adsorption columns (Kaneka) and on-line heparin precipitation (HELP) are the most popular systems used in LDL apheresis. Weekly or biweekly procedures plus concomitant drug therapy enable LDL cholesterol to be maintained at 30–50% of its untreated level, with regression of xanthomas, arrest of progression of coronary atherosclerosis, and improved life expectancy. However, aortic stenosis may progress despite apheresis and necessitate valve replacement. Better control of hypercholesterolemia results from combining apheresis with a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, atorvastatin. LDL apheresis can also be useful in treating drug-resistant FH heterozygotes with coronary disease. However, the FH Regression Study showed no evidence that reduction by apheresis of both LDL and lipoprotein(a), was more advantageous than reduction by combination drug therapy of LDL alone.     

Gender differences in short-term effects of atorvastatin on lipid profile, fibrinolytic parameters, and endothelial function

Background and aimLittle is known about the impact of gender on short-term effects of atorvastatin. We investigated the gender differences in the short-term lipid-lowering and pleiotropic effects of atorvastatin therapy.Methods and resultsSeventy-two consecutive patients including 48 women with primary hypercholesterolemia, were assigned prospectively to treatment with atorvastatin (10 mg/day) for 3 months. We measured fasting lipid concentrations, thiobarbituric acid reactive substances (TBARS) as marker of lipid peroxide, fibrinolytic parameters, and endothelial function by flow-mediated vasodilation of the brachial artery (FMD), at baseline and after 3 months of therapy. We assessed the impact of gender on temporal differences in these parameters.In men, atorvastatin decreased total, low-density lipoprotein (LDL), and small, dense LDL-cholesterol concentrations, and increased FMD after 3 months. In women, atorvastatin decreased TBARS, triglyceride, and total, LDL, small, dense LDL, and remnant-like lipoprotein particle-cholesterol concentrations, and increased FMD after 3 months. Fibrinolytic parameters did not change significantly in either men or women. With respect to the percent change in those parameters after 3 months, TBARS (−17.6 ± 12.4 vs. −0.4 ± 18.8%, p < 0.01) and small, dense LDL-cholesterol (−96.7 ± 8.3 vs. −68.6 ± 29.7%, p < 0.01) decreased to a greater degree in women, although the relative changes in other parameters were similar between men and women.ConclusionsWe found gender differences in some of the lipid altering changes, including TBARS and small, dense LDL-cholesterol concentrations, after short-term atorvastatin therapy, which were greater in women. However, short-term atorvastatin therapy may be beneficial in improving endothelial function equally in both men and women.     

Markers of inflammation and platelet aggregation in patients with non ST elevation acute coronary syndrome treated with atorvastatin or pravastatin

AIM: To find out whether early use of atorvastatin and pravastatin in patients with non-ST elevation acute coronary syndrome is associated with rapid changes of platelet aggregation and plasma levels of markers of inflammation. MATERIAL AND METHODS: Ninety patients (<24h from pain onset, age 64+/-10 years) treated with aspirin and heparin were randomized to open atorvastatin 10 mg/day (n=30), atorvastatin 40 mg/day (n=29) or pravastatin 40 mg/day (n=31). Spontaneous and ADP induced platelet aggregation (light transmission), plasma levels of interleukin 6 (IL-6) and C-reactive protein (CRP) (immunoassay) were assessed at baseline, on days 7 and 14. RESULTS: Baseline clinical characteristics, platelet aggregation parameters, CRP and IL-6 levels were similar in all groups. In all groups levels of total and low-density lipoprotein (LDL) cholesterol (CH) were lowered by days 7 (p<0.01) and 14 (p<0.01 vs. baseline and for both atorvastatin groups vs. day 7). Spontaneous platelet aggregation decreased by 15% from baseline, p<0.01, on day 14 in patients receiving atorvastatin 40 and was unchanged in other groups. Changes of ADP induced platelet aggregation, IL-6 and CRP levels were not significant in all groups. However combination of 2 atorvastatin groups (n=59) revealed decrease of CRP by 18% from baseline on day 14 (from 6.94+/-0.97 to 4.76+/-0.76 mg/l, p=0.028). No correlations were found between changes of LDL CH and those of other parameters. CONCLUSION: In otherwise conventionally treated patients with non-ST elevation acute coronary syndrome early use of atorvastatin was associated with rapid (in 14 days) decrease of CRP level. Higher dose of atorvastatin (40 mg/day) induced favorable changes of spontaneous platelet aggregation. There were no significant changes of parameters studied in pravastatin treated patients.