OBJECTIVE: To determine the effect of different doses of atorvastatin on the serum soluble intercellular adhesion molecules-1 (sICAM-1) in patients undergoing percutaneous coronary intervention (PCI). METHODS: The study consisted of 38 patients with unstable angina and 10 patients with old infarction who underwent elected PCI for stenotic lesions of the coronary artery. Patients were randomly assigned to either aggressive group or conventional one. After PCI the patients took atorvastatin 20 mg per day or 10 mg per day. Blood lipid profile was examined before, and 3 months after the PCI. SICAM-1 was examined before the PCI, 48 hours and 3 months after the PCI. RESULTS: The total cholesterol and LDL-Cholesterol 3 months after the PCI in the 2 groups were lower than those before the PCI (P<0.01). The aggressive group showed greater reduction in concentrations of TC and LDL-C than the conventional group (P<0.01). The changes in concentrations of HDL-C between pre-PCI and 3 months after the PCI and TG were not obvious (P>0.05). sICAM-1 in the 2 groups 48 hours after the PCI significantly higher than that before the PCI (P<0.01). But sICAM-1 in the 2 groups 3 months after the PCI significantly lower than that before the PCI (P<0.01 or P<0.05). The aggressive group showed greater reduction than the conventional group (P<0.01). TC and LDL-C were positively correlated with sICAM-1(r=0.2413, r=0.2691, all P<0.05). CONCLUSION Atorvastatin 20 mg per day reduces TC, LDL-C, and sICAM-1 to a greater extent than atorvastatin 10 mg per day. The effect on sICAM-1 is partly related to reduce lipid profile.
Aged ; Atorvastatin ; Female ; Heptanoic Acids ; administration & dosage ; therapeutic use ; Humans ; Intercellular Adhesion Molecule-1 ; blood ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Pyrroles ; administration & dosage ; therapeutic use

OBJECTIVETo evaluate whether taking atorvastatin for long time has positive effects on age-related renal impairment.

METHODS20-month-age normal female Wistar rats were divided into three groups (n = 9). First group were fed atorvastatin 10 mg/(kg x d). Second group were fed atorvastatin 1 mg/(kg x d). Third group were fed the same volume normal saline served as control. All the rats were sacrificed after four months. 3-month-age normal female Wistar rats (n = 9) also served as normal control. Kidney weight, serum creatinine (Scr) and blood-lipoids were measured. Paraffin sections of renal tissues were stained with PAS and Sirius red. Sclerosis index of glomerulus was calculated.

RESULTSRenal mass diminution was found in all the groups of aging rats. Scr was decreased in the group of aging rats with atorvastatin 1 mg/(kg x d). The level of blood-lipoids of aging rats was higher than that of young rats. The level of serum cholesterol and low-density lipoprotein (LDL) were decreased in first group (both P < 0.05) and only LDL decreased in second group (P < 0.05). Morphological changes of aging kidney were focal segmental glomerulosclerosis, widen of mesangial region, infiltration of inflammatory cells and sclerosis of arteriole. The treatment of atorvastatin improved the pathologic changes in the aging rats significantly, especially in the first group.

CONCLUSIONTaking atorvastatin for long time can notably improve the pathological changes of aging kidney. All these effects may be induced by lowing of blood-lipoids, relieving the sclerosis of renal arteriole and reducing the infiltration of inflammatory cells.

Aging ; physiology ; Animals ; Anticholesteremic Agents ; administration & dosage ; pharmacology ; Arteriosclerosis ; pathology ; prevention & control ; Atorvastatin Calcium ; Female ; Heptanoic Acids ; administration & dosage ; pharmacology ; Kidney ; pathology ; Kidney Diseases ; prevention & control ; Pyrroles ; administration & dosage ; pharmacology ; Rats ; Rats, Wistar ; Renal Artery ; pathology

OBJECTIVETo observe the effect of atorvastatin on eNOS synthesis in the vital organs of aging rats and explore its mechanism for protection against myocardial ischemia-reperfusion injury.

METHODSTwenty-month-old Wistar rats were given daily atorvastatin lavage for 4 months. Myocardial ischemia-reperfusion model was established by ligating the coronary artery. The rats were randomized into normal control group, untreated model group, medication without surgery group, and atorvastatin-treated surgical group. The content of eNOS in the heart, liver and kidneys was detected by Western blotting, and eNOS mRNA expression by RT-PCR. The effects of different doses of atorvastatin on eNOS expressions were also evaluated.

RESULTSAtorvastatin significantly promoted eNOS synthesis in the heart, liver and kidney of the rats (P<0.05) regardless of myocardial ischemia-reperfusion. A higher dose of atorvastatin caused a more obvious increase of eNOS protein and mRNA expression in the vital organs of the aging rats (P<0.05).

CONCLUSIONAtorvastatin can increase eNOS synthesis in the vital organs of aging rats, which partially explains the organ-protective effect of atorvastatin against myocardial ischemia- reperfusion.

Animals ; Atorvastatin Calcium ; Female ; Heptanoic Acids ; administration & dosage ; pharmacology ; Kidney ; metabolism ; Liver ; metabolism ; Male ; Myocardial Reperfusion Injury ; drug therapy ; metabolism ; Myocardium ; metabolism ; Nitric Oxide Synthase Type III ; genetics ; metabolism ; Pyrroles ; administration & dosage ; pharmacology ; Rats ; Rats, Wistar

OBJECTIVETo evaluate the efficacy of atorvastatin in preventing contrast agent-induced nephropathy (CIN) in patients undergoing coronary angiography and explore the mechanism.

METHODSA total of 180 patients undergoing coronary angiography or percutaneous coronary interventions (PCI) were randomized into regular dose and high dose atorvastatin groups (n=90). Serum creatinine (Scr), glomerular filtration rate (GFR), cystatin, peripheral blood levels of myeloperoxidase (MPO), malondialdehyde (MDA), and superoxide dismutase (SOD) before and after the procedure were compared between the two groups.

RESULTSThe incidence of CIN was significantly lower in high-dose atorvastatin group than in the regular dose group. At 48-72 h after the surgery, serum Scr and cystatin levels were significantly lower and eGFR was significantly higher in the high-dose group. At 24 h after the surgery, MPO and MDA levels were significantly lower, and SOD activity was significantly higher in high-dose group than in the regular dose group.

CONCLUSIONHigh-dose atorvastatin used before angiography is more effective than the regular dose in attenuating contrast agent-induced renal dysfunction, and its mechanism is related with the inhibition of oxidative stress.

Aged ; Atorvastatin Calcium ; Contrast Media ; adverse effects ; Coronary Angiography ; adverse effects ; Female ; Heptanoic Acids ; administration & dosage ; pharmacology ; therapeutic use ; Humans ; Kidney Diseases ; chemically induced ; prevention & control ; Male ; Middle Aged ; Oxidative Stress ; drug effects ; Pyrroles ; administration & dosage ; pharmacology ; therapeutic use

OBJECTIVETo compare the efficacy of high and low dose atorvastatin on preventing contrast induced nephropathy (CIN) in patients underwent diagnostic and therapeutic coronary intervention.

METHODSAll patients received atorvastatin 10 mg/d on the basis of hydrated therapy (n = 100) and high dose group received additional atorvastatin 80 mg at 12 to 24 hours before procedure (n = 50). Scr, Ccr, blood beta(2)-M, urine NAG/Cr, and urine osmolality before and after the procedure were compared between the groups.

RESULTSBaseline demographic characteristics and nephropathy risk factors were similar between groups. Ccr was significantly reduced while blood beta(2)-M and uric NAG/Cr were significantly increased in low dose group (all P < 0.05). Blood beta(2)-M in the high dose group was significantly lower than that in the low dose group at day 1 [(2.35 +/- 0.52) mg/L vs. (2.67 +/- 0.64) mg/L, P = 0.008], day 3 [(2.49 +/- 0.55) mg/L vs. (2.80 +/- 0.64) mg/L, P = 0.011] and day 5 [(2.29 +/- 0.53) mg/L vs. (2.56 +/- 0.66) mg/L, P = 0.026] post-procedure respectively;urine NAG/Cr in the high dose group was also significantly lower than that in the low dose group at day 1 [(1.19 +/- 0.30) U/mmol vs. (1.46 +/- 0.34) U/mmol, P < 0.001], day 3 [(1.30 +/- 0.30) U/mmol vs. (1.59 +/- 0.33) U/mmol, P < 0.001], and day 5 [(1.10 +/- 0.30) U/mmol vs. (1.34 +/- 0.35) U/mmol, P = 0.001] post-procedure respectively;Ccr in the high dose group was significantly higher than that in the low dose group at day 1 [(73.69 +/- 20.99) ml/min vs. (65.19 +/- 18.72) ml/min, P = 0.035], day 3 [(64.04 +/- 15.82) ml/min vs. (56.79 +/- 14.50) ml/min, P = 0.019]post-procedure respectively.

CONCLUSIONHigh dose atorvastatin use before angiography is superior than low dose atorvastatin on attenuating contrast induced renal dysfunction.

Aged ; Atorvastatin Calcium ; Contrast Media ; adverse effects ; Coronary Angiography ; methods ; Female ; Heptanoic Acids ; administration & dosage ; therapeutic use ; Humans ; Kidney Diseases ; chemically induced ; prevention & control ; Kidney Failure, Chronic ; chemically induced ; prevention & control ; Male ; Middle Aged ; Pyrroles ; administration & dosage ; therapeutic use

BACKGROUND/AIMS: This multicenter, open-labeled, randomized trial was performed to compare the effects of rosuvastatin 10 mg and atorvastatin 10 mg on lipid and glycemic control in Korean patients with nondiabetic metabolic syndrome. METHODS: In total, 351 patients who met the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria for metabolic syndrome with low-density lipoprotein cholesterol (LDL-C) levels > or = 130 mg/dL were randomized to receive either rosuvastatin 10 mg (n = 173) or atorvastatin 10 mg (n = 178) for over 6 weeks. RESULTS: After 6 weeks of treatment, greater reductions in total cholesterol (- 35.94 +/- 11.38 vs. - 30.07 +/- 10.46%, p < 0.001), LDL-C (48.04 +/- 14.45 vs. 39.52 +/- 14.42%, p < 0.001), non-high-density lipoprotein cholesterol (- 42.93 +/- 13.15 vs. - 35.52 +/- 11.76%, p < 0.001), and apolipoprotein-B (- 38.7 +/- 18.85 vs. - 32.57 +/- 17.56%, p = 0.002) levels were observed in the rosuvastatin group as compared to the atorvastatin group. Overall, the percentage of patients attaining the NCEP ATP III goal was higher with rosuvastatin as compared to atorvastatin (87.64 vs. 69.88%, p < 0.001). Changes in glucose and insulin levels, and homeostasis model assessment of insulin resistance index were not significantly different between the two groups. The safety and tolerability of the two agents were similar. CONCLUSIONS: Rosuvastatin 10 mg was more effective than atorvastatin 10 mg in achieving NCEP ATP III LDL-C goals in patients with nondiabetic metabolic syndrome, especially in those with lower NCEP ATP III target level goals.
Blood Glucose/metabolism ; Cholesterol, LDL/blood ; Female ; Fluorobenzenes/*administration & dosage ; Hemoglobin A, Glycosylated/metabolism ; Heptanoic Acids/*administration & dosage ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & dosage ; Hypercholesterolemia/blood/complications/*drug therapy ; Hyperglycemia/blood/complications/*drug therapy ; Insulin/blood ; Male ; Metabolic Syndrome X/blood/complications/*drug therapy ; Middle Aged ; Pyrimidines/*administration & dosage ; Pyrroles/*administration & dosage ; Sulfonamides/*administration & dosage ; Treatment Outcome

AIMTo prepare self-microemulsifying drug delivery system (SMEDDS) containing atorvastatin,and decrease its size to improve the solubility in the stomach. And to study the effect of the resultant microemulsion in reducing the presystemic clearance in the gastrointestinal mucosa and hepatic first-pass metabolism, improving the oral bioavailability, and reducing side effect and expenditure.

METHODSPseudoternary phase diagrams were used to evaluate the self-microemulsification existence area. The HPLC analyses in vitro and in vivo were set up. Solubility in various vehicles was determined. The self-microemulsification efficiency was assessed, such as self-microemulsification time, stability, particle size and zeta potential. SMEDDS containing atorvastatin, non-ionic surfactant and lipid were prepared. Droplet size/distributions and zeta potential of the resultant microemulsion were determined. Photos were taken with transmission electron microscope. Oral bioavailability was studied on prepared SMEDDS hard capsules and compared with that of the conventional tablet in Beagle dogs in vivo.

RESULTSThe optimal formulations had wide microemulsion existent field and had good self-microemulsifying efficiency. Droplet size was within 100 nm and showed Gaussian distribution. After oral administration of SMEDDS capsules and the conventional tablet to fasted Beagle dogs, the Cmax from SMEDDS was greater than that of the conventional tablet. AUC from zero to 24 h of SMEDDS was about 1.5-fold higher than that of the conventional tablet. Oral bioavailability of atorvastatin SMEDDS was greater than that of the conventional tablet.

CONCLUSIONThe results indicated the potential use of SMEDDS for the delivery of atorvastatin to increase its oral bioavailability.

Administration, Oral ; Animals ; Area Under Curve ; Atorvastatin Calcium ; Biological Availability ; Dogs ; Drug Delivery Systems ; Emulsions ; Glycerol ; analogs & derivatives ; chemistry ; Heptanoic Acids ; administration & dosage ; blood ; pharmacokinetics ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; administration & dosage ; blood ; pharmacokinetics ; Male ; Particle Size ; Polyethylene Glycols ; chemistry ; Pyrroles ; administration & dosage ; blood ; pharmacokinetics ; Solubility

INTRODUCTIONWe aimed to assess the efficacy of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia.

METHODSA double-blind study was conducted to assess the effect of fixed dose combination of ezetimibe 10 mg plus atorvastatin 10 mg on lipid profile, oxidised low-density lipoprotein (ox-LDL), high-sensitivity C-reactive protein (hsCRP) and soluble intercellular cell adhesion molecule (sICAM) in dyslipidaemic patients with or at high risk of coronary artery disease, and compare it with atorvastatin 10 mg monotherapy. 30 patients were randomised to receive ezetimibe plus atorvastatin or atorvastatin once daily for four weeks.

RESULTSOf the 30 patients, 10 men and 5 women (mean age 54.3 ± 1.6 years) received ezetimibe plus atorvastatin, while 13 men and 2 women (mean age 53.7 ± 2.8 years) received only atorvastatin. The combination treatment significantly reduced total cholesterol (percentage treatment difference -14.4 ± 6.5, 95% confidence interval [CI] -1.0 to -27.7; p = 0.041) and LDL cholesterol (LDL-C; percentage treatment difference -19.9 ± 6.1, 95% CI -7.4 to -32.4; p = 0.003) compared to atorvastatin monotherapy. 13 patients on combination treament achieved the National Cholesterol Education Program target for LDL-C as compared to 9 patients on atorvastatin monotherapy (p = 0.032). Significant reductions in very low-density lipoprotein cholesterol, triglyceride, ox-LDL and sICAM were observed with combination treatment compared to atorvastatin monotherapy. However, no significant change was seen in high-density lipoprotein cholesterol or hsCRP levels between the two groups.

CONCLUSIONCombination treatment with atorvastatin and ezetimibe had relatively better lipid-lowering and anti-inflammatory efficacy than atorvastatin monotherapy.

Anti-Inflammatory Agents ; therapeutic use ; Anticholesteremic Agents ; administration & dosage ; Atorvastatin Calcium ; Azetidines ; administration & dosage ; C-Reactive Protein ; metabolism ; Double-Blind Method ; Drug Therapy, Combination ; methods ; Dyslipidemias ; drug therapy ; Ezetimibe ; Female ; Heptanoic Acids ; administration & dosage ; Humans ; Hypolipidemic Agents ; therapeutic use ; India ; Intercellular Adhesion Molecule-1 ; metabolism ; Lipoproteins, LDL ; metabolism ; Male ; Middle Aged ; Pyrroles ; administration & dosage ; Treatment Outcome

BACKGROUNDAlzheimer's disease (AD) is a neurodegenerative disorder and the leading cause of dementia in the elderly. The two hallmark lesions in AD brain are deposition of amyloid plaques and neurofibrillary tangles (NFTs). Hypercholesteremia is one of the risk factors of AD. But its role in the pathogenesis of AD is largely unknown. The aim of this study was to investigate the relationship between hypercholesteremia and tau phosphorylation or beta-amyloid (Abeta), and evaluate the effect of atorvastatin on the level of tau phosphorylation and Abeta in the brains of rats fed with high cholesterol diet.

METHODSSprague-Dawley (SD) rats were randomly divided into normal diet control group, high cholesterol diet group, and high cholesterol diet plus atorvastatin (Lipitor, 15 mg x kg(-1) x d(-1)) treated group. Blood from caudal vein was collected to measure total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high-density lipoprotein (HDL) at the end of the 3rd and the 6th months by an enzymatic method. The animals were sacrificed 6 months later and brains were removed. All left brain hemispheres were fixed for immunohistochemistry. Hippocampus and cerebral cortex were separated from right hemispheres and homogenized separately. Tau phosphorylation and Abeta in the brain tissue were determined by Western blotting (using antibodies PHF-1 and Tau-1) and anti-Abeta40/anti-Abeta42, respectively.

RESULTSWe found that high cholesterol diet led to hypercholesteremia of rats as well as hyperphosphorylation of tau and increased Abeta level in the brains. Treatment of the high cholesterol diet fed rats with atorvastatin prevented the changes of both tau phosphorylation and Abeta level induced by high cholesterol diet.

CONCLUSIONSHypercholesteremia could induce tau hyperphosphorylation and Abeta production in rat brain. Atorvastatin could inhibit tau hyperphosphorylation and decrease Abeta generation. It may play a protective role in the patho-process of hypercholesteremia-induced neurodegeneration in the brain.

Administration, Oral ; Amyloid beta-Peptides ; metabolism ; Animals ; Antibodies, Monoclonal ; Atorvastatin Calcium ; Blotting, Western ; Brain ; drug effects ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Heptanoic Acids ; administration & dosage ; pharmacology ; therapeutic use ; Immunohistochemistry ; Male ; Phosphorylation ; drug effects ; Pyrroles ; administration & dosage ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; tau Proteins ; metabolism

OBJECTIVETo observe the association between preprocedural high sensitivity C-reactive protein (hs-CRP) level and incidence of contrast induced acute kidney injury (CI-AKI) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) and the impact of atorvastatin pretreatment on CI-AKI.

METHODSAccording to the level of preprocedural hs-CRP, 270 ACS patients were divided into three groups: high hs-CRP group (hs-CRP ≥ 3 mg/L, n = 176), moderate hs-CRP group (hs-CRP 1-3 mg/L, n = 60) and normal hs-CRP group (hs-CRP < 1 mg/L, n = 34). According to the dosage of preprocedural atorvastatin, the high hs-CRP group was further divided into 10 mg group (n = 49), 20 mg group (n = 66) and 40 mg group (n = 61). Serum creatinine (Scr), blood urea nitrogen (BUN), cystatin C (Cys C), hs-CRP were measured at before and 24 hours, 48 hours after PCI. CCr and GFR were calculated according to Scr and Cys C. Risk factors for CI-AKI were determined by multivariate logistic regression analysis.

RESULTS(1) Cys C was significantly increased and GFR after PCI significantly reduced in high and moderate hs-CRP groups compared with normal hs-CRP group (P < 0.05). (2) Incidence of CI-AKI was 43.18%, 38.33%, 20.59% in high, moderate and normal hs-CRP groups, respectively (P < 0.05). (3) In high hs-CRP group, postprocedural GFR was significantly higher while postprocedural Cys C and hs-CRP were significantly lower in 40 mg statin subgroup than 10 mg and 20 mg statin subgroups (P < 0.05), similar trends were documented when comparing 20 mg statin subgroup with 10 mg statin subgroup (P < 0.05). (4) Multivariate logistic regression analysis showed that pretreatment with high dose atorvastatin was a protective factor for post CI-AKI (20 mg atorvastatin: OR = 0.15, 95%CI 0.06 - 0.33, P = 0.001; 40 mg atorvastatin: OR = 0.10, 95%CI 0.04 - 0.23, P = 0.001), while high levels of preprocedural hs-CRP (OR = 2.06, 95%CI 1.01 - 4.23, P = 0.048), diabetes mellitus (OR = 10.71, 95%CI 5.29 - 21.70, P = 0.001), advanced age (OR = 2.64, 95%CI 1.05 - 6.63, P = 0.038) and renal failure (OR = 5.14, 95%CI 1.13 - 23.39, P = 0.034) were independent risk factors of CI-AKI.

CONCLUSIONHigh hs-CRP level is linked with the development of CI-AKI in ACS patients undergoing PCI and pretreatment with 40 mg atorvastatin is associated with lower incidence CI-AKI, possibly by reducing the postprocedural inflammation responses.

Acute Coronary Syndrome ; drug therapy ; metabolism ; Acute Kidney Injury ; etiology ; Aged ; Angioplasty, Balloon, Coronary ; Atorvastatin Calcium ; C-Reactive Protein ; metabolism ; Contrast Media ; adverse effects ; Female ; Heptanoic Acids ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Pyrroles ; administration & dosage ; therapeutic use