Introduction: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, named statins, are well-established cholesterol lowering drugs able to reduce cardiovascular risk in hypercholesterolemic patients. The possible effect of statin on bone tissue, so-called pleiotropic effects has received particular attention. Studies reported a positive effect of statin on bone tissue in both of animal and human study by enhancing the expression of the bone morphogenetic proteins (BMPs), in particular of BMP2, which in turn leads to osteoblast differentiation and bone formation including interfering with osteoclastic activity. In a systematic review, the lipophilic statin as simvastatin had positive effect to bone mineral density (BMD) better than the more hydrophilic statin such as atorvastatin and fluvastatin. This study was aimed to compare efficacy of medical therapy between HMG-CoA reductase inhibitor and Non-HMG-CoA reductase inhibitor group to changing of bone mineral density and bone markers in the patients with hyperlipidemia. Materials and methods: A prospective randomized control trial study was enrolled the 212 hyperlipidemia with osteopenia patients to study in year 2006-2008. All subjects were randomized to 2 groups between statin and non-statin group the patients were screened by inclusion criteria and measured in bone mineral density (BMD), bone marker and blood chemistry. All data were analyzed by difference of changing in bone marker and BMD between statin and non-statin groups using paired T-test. Results: The present study showed 212 hyperlipidemia with osteopenia patients which of 106 patients in statin group had mean age (63.17 + 9.51 years) and the same number of patients in non-statin group had mean age (60.96 + 8.9 years). All subjects were 63 patients in male and 149 patients in female. Difference of bone formation marker and BMD between after and before was significantly higher than in statin group and the difference of bone resorption marker was also significantly lower than in statin group Conclusion: The lipophilic statin as moderate to high dose of simvastatin had beneficial positive effect to increasing BMD and could be additive use for prevention of bone loss in hyperlipidemia patients. less...

BACKGROUND: The combination of niacin and statin has proven value in hyperlipidemia management and heart disease prevention. However, the efficacy of the non-prescription time-release niacin, Slo-Niacin(R), is little studied alone and not at all with atorvastatin. We gave Slo-Niacin(R) and atorvastatin, singly and together to determine efficacy on the combined abnormalities of triglyceride, LDL and HDL. METHODS: 42 men and women with LDL-C>130mg/dL HDL-C <45 (men or 55mg/dL (women) were randomized to 3 months of atorvastatin 10 mg/day or incremental doses of Slo-Niacin(R) to 1500 mg/day. The alternate drug was added in the next 3-month segment. Lipid profiles and transaminases were measured monthly and other measures at baseline and the end of each treatment sequence. RESULTS: Mean entry lipids (mg/dL) were: TG 187, LDL-C 171, and HDL-C 39. Mean BMI was 32.6 Kg/m(2). Monotherapy with Slo-Niacin(R) decreased median triglyceride 15%, mean LDL-C 12% and non-HDL-C 15% and increased HDL-C 8%. Atorvastatin decreased median triglyceride 26%, and mean LDL-C 36%, non-HDL-C 36% and increased HDL-C 6%. Combined therapy decreased median triglyceride 33% and mean LDL-C and non-HDL-C each 43%. HDL-C increased 10% (all p<0.001). Median remnant-like lipoprotein-C decreased 55%, mean apo-B 40%, median hsCRP 23% (all p<0.05), TNFa 12% and no change in IL-6. Mean LDL buoyancy increased 15%, apo-A-I 5% and median HDL(2)-C 20% (all p<0.05). ALT declined with Slo-Niacin(R) treatment alone compared to atorvastatin and also decreased when Slo-Niacin(R) was added to atorvastatin. Six subjects dropped out, 3 for niacin related symptoms. CONCLUSIONS: Slo-Niacin(R) 1.5g/day with atorvastatin 10 mg/day improved lipoprotein lipids, apoproteins and inflammation markers without hepatotoxicity. Slo-Niacin(R) deserves further study as a cost-effective treatment of hyperlipidemia. less...

Epidemiology studies suggest that statins and nonsteroidal anti-inflammatory drugs reduce the risk of prostate cancer. In the present study, LNCaP cells were cultured in regular medium containing fetal bovine serum or in medium supplemented with charcoal-stripped fetal bovine serum to mimic androgen deprivation treatment. We found that atorvastatin (Lipitor) or celecoxib (Celebrex) treatment of LNCaP cells cultured in regular or androgen-depleted medium inhibited growth and stimulated apoptosis. A combination of atorvastatin and celecoxib was more effective than either agent alone. In animal studies, severe combined immunodeficient mice were injected s.c. with LNCaP cells in Matrigel. After 4 to 6 weeks, mice with LNCaP tumors (about 0.6 cm wide and 0.6 cm long) were surgically castrated and received daily i.p. injections of vehicle, atorvastatin (10 microg/g body weight/d), celecoxib (10 microg/g/d), or a combination of atorvastatin (5 microg/g/d) and celecoxib (5 microg/g/d) for 42 days. In all groups, the androgen-dependent LNCaP tumors regressed initially in response to castration, but the tumors eventually progressed to androgen independence and started to grow. Treatment of the mice with atorvastatin or celecoxib alone suppressed the regrowth of LNCaP tumors after castration. A combination of low doses of atorvastatin and celecoxib had a more potent effect in inhibiting the growth and progression of LNCaP tumors to androgen independence than a higher dose of either agent alone. Our results indicate that administration of a combination of atorvastatin and celecoxib may be an effective strategy for the prevention of prostate cancer progression from androgen dependence to androgen independence. less...

Statins improve cardiovascular survival in both nondiabetic and diabetic patients, but diabetic patients benefit more, in both primary and secondary prevention. Statins seem to have multiple effects beyond cholesterol lowering, that is, pleiotropic effects that may include changes in renal function. This study tests the hypothesis that acute treatment with atorvastatin may change glomerular filtration rate, tubular function, vasoactive hormones, blood pressure, and pulse rate in patients with type 2 diabetes. In an acute, randomized, placebo-controlled, double-blinded, crossover trial, the effects of atorvastatin on renal function, vasoactive hormones, blood pressure, and pulse rate are measured in 21 patients with type 2 diabetes. Patients are randomized to either 2 doses of atorvastatin 80 mg or placebo before 2 different study days. Treatment with atorvastatin induces a significant reduction in fractional sodium excretion compared with placebo, and sodium clearance tends to be reduced. No significant differences in glomerular filtration rate, albumin/creatinine ratio, vasoactive hormones, and blood pressure by acute treatment with atorvastatin are found in diabetic patients. Acute treatment with atorvastatin reduces renal fractional sodium excretion in patients with type 2 diabetes. No changes are measured in glomerular filtration rate, albumin/creatinine ratio, vasoactive hormones, and blood pressure. less...

A multicenter study was conducted to assess the efficacy of a generic form of Atorvastatin (Ranbaxy's Storvas) in the treatment of Primary Hypercholesterolemia. One hundred and nineteen patients were given 10 mg of Storvas for four weeks and increased to 20 mg if target LDL-Cholesterol was not achieved. LDL-Cholesterol was reduced by 36.6% at four weeks and 37.5% at eight weeks from baseline. Total cholesterol and triglycerides were significantly reduced. There were no drug-related serious adverse events. We conclude that the generic atorvastatin is safe and effective in the treatment of primary hypercholesterolaemia and the results are comparable to published data on innovator atorvastatin. less...

BACKGROUND: The SR-BI is a key component on the cholesterol metabolism. Polymorphisms in the SR-BI gene (SCARB1) were related with variations on plasma lipoprotein profile and other risk factors for cardiovascular disease. We tested the relationship of 3 SCARB1 single nucleotide polymorphisms (SNPs) with hypercolesterolemia in a Brazilian population and whether these variants can influence lipid-lowering response to atorvastatin. METHODS: c.4G>A, c.726+54C>T and c.1050C>T SNPs and serum concentrations of lipid and apolipoproteins were evaluated in 147 hypercolesterolemic (HC) and 185 normolipidemic (NL) unrelated Brazilian subjects. HC patients were treated with atorvastatin (10mg/day/4weeks). RESULTS: Frequencies of SCARB1 polymorphisms were similar between HC and NL groups (p>0.05). The T allele for c.726+54C>T was associated with higher LDL-c in NL and with higher apoB and apoB/apoAI in HC (p<0.05). HC individuals carrying c.1050C allele carriers (CC and CT genotypes) had lower change of total cholesterol, LDL-c, apoB and apoB/apoAI ratio (p<0.05) than the TT genotype carriers in response to atorvastatin. CONCLUSION: The SCARB1 polymorphisms are related with variations in serum lipids in Brazilian population and c.1050C>T SNP is associated with lipid-lowering atorvastatin response. less...

Aim: The clinical relevance of the suggested pleiotropic effects of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) is controversial. Aggressive statins effectively reduce lipid levels, but whether their other effects are more powerful than those of regular statins is unknown.Methods: We enrolled 32 patients (mean age, 65 y; male, 23) who had undergone coronary revascularization over 6 months previously and whose serum LDL cholesterol levels persisted at >100 mg/dL, regardless of pravastatin (10 mg/day). Before and 1 and 6 months after switching to atorvastatin (10 mg/day), we evaluated lipid profiles, including RLP-C (remnant-like particle cholesterol), high sensitive CRP (hsCRP), soluble CD40 ligand (sCD40L), TBARS (thiobarbituric acid reactive substances), and endothelial function determined from flow-mediated dilation (FMD) of the brachial artery.Results: One month on atorvastatin lowered LDL cholesterol by 24% (131 to 100 mg/dL, p<0.001). In addition, RLP-C, sCD40L and hsCRP significantly decreased, whereas FMD did not change. After 6 months of this therapy, FMD significantly improved compared to baseline values (5.1 vs 3.6%, p=0.04). Changes in FMD and in total and RLP cholesterol significantly correlated. Moreover, FMD was remarkably improved in patients who achieved target LDL levels (<100 mg/dL).Conclusions: Switching from a regular to an aggressive statin can improve endothelial function at 6 months in patients with previous coronary artery disease. This effect is suggested to be mainly due to the lipid-lowering effect. Achievement and maintenance of the target LDL level by switching statins is beneficial in the clinical setting. less...

Patients with type 2 diabetes mellitus have a high risk of developing cardiovascular (CV) disease. The clinical benefit of use of statins in patients with type 2 diabetes has been demonstrated in several randomized, controlled trials, including the CARDS clinical trial. Based on the clinical CARDS data, the favourable cost effectiveness of atorvastatin 10 mg in patients with type 2 diabetes has been demonstrated in countries such as the UK and France. This study aimed to estimate the cost effectiveness in the Belgian setting of atorvastatin 10 mg compared with no treatment for the primary prevention of CV events in type 2 diabetes patients without a history of CV disease. A Markov model with 1-year cycles was developed to simulate the CV event and death risk according to the therapeutic approach initiated. The transition probabilities for CV events in the 'no statin treatment' group were derived from the risk equations reported from the large UKPDS. Risk reductions from the CARDS clinical trial were used to adjust these CV event probabilities in the atorvastatin 10 mg treatment group. The characteristics of type 2 diabetes patients without a CV history were derived from the Belgian OCAPI survey. The public healthcare payers' perspective was taken into account for costing. The direct medical costs of CV events were based on the Public Health Authorities' hospital database for acute care costs and on the literature for the follow-up costs. The impact on the reimbursement system of generic entry to the market was considered in the drug cost. Costs were valued as at year 2009; costs and outcomes were discounted at 3% and 1.5%, respectively. Based on a 5-year time horizon, atorvastatin was demonstrated to be cost effective with an incremental cost/quality-adjusted life-year (QALY) of euro16 681. Over a lifetime horizon (25 years), atorvastatin was demonstrated to be a cost-saving therapeutic intervention. At a threshold of euro30 000/QALY, atorvastatin had a 98.8% probability of being cost effective. Compared with 'no treatment', use of atorvastatin 10 mg as a primary prevention intervention in Belgian type 2 diabetes patients not only improves CV outcomes, but also appears to be cost saving over a lifetime horizon. less...

Background/Aims: Aims of the present study are to examine the effects of atorvastatin administration and the influence of membrane flux on adhesion molecules expression on monocytes. Methods: We studied CD11b, CD18 and CD62L expression on monocytes (flow cytometry) in 32 patients, 16 on low-flux (LFD) and 16 on high-flux (HFD) polysulfone hemodialysis, before and after dialysis and also after administration of atorvastatin 20 mg/day for 6 months. Results: After hemodialysis, expression of CD11b and CD18 increased and expression of CD62L decreased. After atorvastatin administration there was a decrease in pre-dialysis monocyte expression of CD11b and CD18, and an increase in the expression of CD62L compared to pre-dialysis baseline values. There were no statistically significant differences in expression of all three molecules between LFD and HFD groups. Conclusions: Polysulfone dialysis process activates monocytes irrespectively of the membrane flux. Atorvastatin use is associated with reduced monocyte activation. less...

Abstract Aims. The aim of the study was to determine whether a high dose of atorvastatin lowers blood pressure (BP) in normolipemic patients with well controlled primary arterial hypertension and if this effect is associated with alteration of biomarkers of endothelial function and oxidative stress. In this open-label study, normolipemic patients (n=56) were randomized in the proportion of 2:1 to receive atorvastatin 80 mg daily for 3 months (statin-treated, ST n=39), or to previous therapy (statin-free, SF). BP was measured using a 24-h ambulatory BP measurement device. Plasma levels of 6-keto-PGF(1alpha) (prostacyclin metabolite), serum nitric oxide (NO) and levels of autoantibodies immunoglobulin G against oxidatively modified low-density lipoprotein (ox-LDL) were measured. Major findings. The mean change in systolic BP and diastolic BP for ST was - 5.7 mmHg (95% CI -4.1 to -7.2 mmHg) and -3.9 mmHg (95% CI -2.7 to -5.0 mmHg), respectively. Hypotensive statin effect was independent of lipid lowering. No change of BP in SF patients was observed. In ST, prostacyclin metabolites and NO concentrations were not significantly increased and autoantibodies against ox-LDL concentrations did not change. In ST, the decrease in BP correlated with increase in NO and decrease in autoantibodies against ox-LDL. Principal conclusion. High-dose atorvastatin resulted in reduction of BP independently of lipid-lowering effect, changes in endothelial function and oxidative stress, but it was related to the increase in NO and decrease in autoantibodies against ox-LDL. However, because of the open design of the study, these results should be carefully debated. less...