atorvastatin Lipitor
Effects of Atorvastatin on some inflammatory parameters in severe primary hypercholesterolemia.

Dobreanu M, Galateanu C, Simionescu A, Deac R.

Department of Clinical Biochemistry, U.M.P. Tirgu Mures, Gh. Marinescu 38, 4300 Tirgu Mures.

Recent publications have reanimated the point of view that there exist links between atherosclerosis--inflammation and hypercholesterolemia. The aim of our study was to investigate the possible influence of statins on some inflammatory parameters in persons with severe primary hypercholesterolemia (PHC). The effects of the HMG CoA reductase inhibitor--Atorvastatin--on serum lipids, apoproteins, C reactive protein (CRP), soluble Intercellular Adhesion Molecule (sICAM), lipid peroxides, antibodies to oxidized LDL (Ab oxLDL) and homocystein were evaluated in 21 persons (52.9 +/- 8.38 years old) with severe PHC, 12 of these having significant coronary-artery stenosis (diameter stenosis > or = 70%), in at least one major coronary artery branch. Ab oxLDL, sICAM, TBARS, CRP and homocystein were significantly increased (p < 0.05) in patients with coronary-artery stenosis. Following a 4 weeks hypolipemiant free baseline period, all persons were treated with Atorvastatin 40 mg once daily for 8 weeks. Atorvastatin 40 mg resulted in a reduction of LDL-C with 57.8% (baseline 259.6 +/- 71.39 mg%) p < 0.001, total Cholesterol with 44.08% (baseline 343.1 +/- 71.72 mg%) p < 0.001, Apo B with 50.6% (baseline 194.7 +/- 48.71 mg%) p < 0.001, TG with 12.02% (baseline 177.4 +/- 83.63 mg%) and HDL-C was increased with 6.84% (baseline 48.0 +/- 7.86 mg%). In coronary heart disease patients, Atorvastatin reduced homocystein concentrations with 19.41% (baseline 17.7 +/- 11.16 microM/l) (p < 0.01), and CRP with 21.9% (baseline 4.8 +/- 4.19 mg/l) p < 0.01 and TBARS with 52% (baseline 0.87 +/- 0.89 nM/ml) p < 0.001, but did not influence sICAM and Ab oxLDL. Thus atherogenic concentrations of LDL-C have to be closely modulated by minimal changes in LDL oxidative state. The effects of Atorvastatin on inflammatory parameters may crucially contribute to the clinical benefit of statins, independent of cholesterol lowering. Plaque stabilization may be a paradigm for antiinflammatory mechanism of action by this class of drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15526541&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
Differential effects of fenofibrate versus atorvastatin on the concentrations of E-selectin and vascular cellular adhesion molecule-1 in patients with type 2 diabetes mellitus and mixed hyperlipoproteinemia: a randomized cross-over trial.

Empen K, Frost RJ, Geiss HC, Otto C, Parhofer KG.

Department of Internal Medicine B, University of Greifswald, Germany. Klaus.Empen t-online.de

BACKGROUND: Diabetic dyslipoproteinemia is characterized by hypertriglyceridemia, low HDL-cholesterol and often elevated LDL-cholesterol and is a strong risk factor for atherosclerosis. Adhesion molecule levels are elevated both in hyperlipoproteinemia and diabetes mellitus. It is unclear whether fibrate or statin therapy has more beneficial effects on adhesion molecule concentrations. METHODS: Atorvastatin (10 mg/d) was compared to fenofibrate (200 mg/d) each for 6 weeks separated by a 6 week washout period in 11 patients (6 male, 5 female; 61.8 +/- 8.2 years; body mass index 29.8 +/- 3.1 kg/m2) with type 2 diabetes mellitus (HbA1c 7.3 +/- 1.1 %) and mixed hyperlipoproteinemia using a randomized, cross-over design. Fasting blood glucose, HbA1c, lipid parameters, E-selectin, ICAM-1, VCAM-1, and fibrinogen concentrations were determined before and after each drug. RESULTS: Glucose and HbA1c concentrations remained unchanged during the whole study period. LDL cholesterol was reduced during atorvastatin therapy, triglycerides were lowered more effectively with fenofibrate. Comparison of pre- and postreatment concentrations of E-selectin showed a reduction during atorvastatin (-7 %, p = 0.11) and fenofibrate (-10 %, p < 0.05) therapy. Atorvastatin treatment reduced VCAM-1 levels by 4% (p < 0.05), while VCAM-1 concentrations remained unchanged (+1%, ns) during fenofibate therapy. However, direct comparisons of post-treatment levels during both forms of therapy were not of statistical significance. ICAM-1 levels were not influenced by either form of therapy. CONCLUSIONS: In addition to the different beneficial effects on lipid metabolism, both drugs appear to lower adhesion molecule plasma concentrations in a different manner in patients with type 2 diabetes and mixed hyperlipoproteinemia. Our observations should be confirmed in a larger cohort of such patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14662011&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
[Atorvastatin lowers C-reactive protein in dislipemic patients with type 2 diabetes mellitus]

[Article in Spanish]

Illan Gomez F, Alcaraz Tafalla MS, Pascual Diaz M, Carrillo Alcaraz A.

Seccion de Endocrinologia y Nutricion, Hospital Universitario Morales Meseguer, Murcia, Spain. mariaf.illan carm.es

BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus is associated with an augmented risk for cardiovascular disease. The levels of C-reactive protein (CRP), the prototypic marker of inflammation, are associated with an increased risk for cardiovascular events. The statins have direct anti-inflammatory effects. Thus, we tested the effects of atorvastatin on levels of CRP on patients with type 2 diabetes. PATIENTS AND METHOD: We evaluated CRP in baseline and 6 months after onset of 20 mg daily atorvastatin therapy of 30 patients with type 2 diabetes with hyperlipidemia. Clinical and biochemical data were obtained. RESULTS: CRP-levels were significantly decreased after treatment with atorvastatin compared with baseline (median change: -4,99 mg/l; p < 0.001). We observed an correlation between CRP baseline with body mass index (r = 0.429; p = 0.018), serum fibrinogen (r = 0.607; p = 0.001) and microalbuminuria (r = 0.470; p = 0.01). Conversely, there was no significant correlation between CRP baseline with LDL cholesterol. The CRP reduction was significantly correlated with fasting glucose (r = -0.457; p = 0.019) and glycosylated hemoglobin at 6 months (r = -0.421; p = 0.03). CONCLUSIONS: These results confirm findings from previous studies that atorvastatin reduce CRP levels in a largely LDL cholesterol independent manner.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15535926&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
Atorvastatin ameliorates renal tissue damage in unilateral ureteral obstruction.

Mizuguchi Y, Miyajima A, Kosaka T, Asano T, Asano T, Hayakawa M.

From the Departments of Urology, National Defense Medical College, Saitama and Keio University School of Medicine (AM), Tokyo, Japan.

PURPOSE:: The current study was done to determine whether atorvastatin, the HMGCoA (3-hydroxy-3-methylglutaryl CoA) reductase inhibitor, could decrease renal transforming growth factor-beta (TGF-beta) levels in unilateral ureteral obstruction (UUO) and concomitantly affect renal tissue damage in UUO. MATERIALS AND METHODS:: Atorvastatin (20 mg/kg) was administered to rats 1 day prior to UUO and every day thereafter. Kidneys were harvested at day 14 after UUO. Tissue TGF-beta was measured by bioassay using mink lung epithelial cells. Renal tubular proliferation and apoptosis were detected by immunostaining proliferating cell nuclear antigen and polyclonal antisingle strand DNA antibody, respectively. Fibrosis was assessed by measuring collagen deposition with trichrome stained slides. Interstitial leukocyte was detected by immunostaining CD45. RESULTS:: TGF-beta bioassay showed that the obstructed kidney in the control group contained significantly higher TGF-beta than the unobstructed kidney in the control group (mean +/- SD 79.1 +/- 48.5 vs 28.7 +/- 13.7 pg/mg tissue) and atorvastatin significantly decrease tissue TGF-beta in the obstructed kidney (53.4 +/- 37.0 pg/mg tissue). Immunostaining polyclonal antisingle strand DNA antibody demonstrated that the obstructed kidney in the control group has significantly more tubular apoptosis than the unobstructed counterpart (4.8 +/- 2.8 vs 2.1 +/- 1.2 nuclei per high power field) and atorvastatin significantly decreased renal tubular apoptosis in the obstructed kidney (1.1 +/- 0.7 nuclei per high power field). In addition, immunostaining proliferating cell nuclear antigen showed that the obstructed kidney in the atorvastatin group had significantly more renal tubular proliferation than the obstructed kidney in the control group (48.7 +/- 20.8 vs 17.3 +/- 10.6 per high power field). Control obstructed kidney showed significantly more fibrosis, which was also blunted by atorvastatin. CONCLUSIONS:: Atorvastatin significantly decreases tissue TGF-beta, resulting in a decrease in tubular damage and interstitial fibrosis. This suggests that atorvastatin is a promising agent for preventing renal tubular damage in UUO.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15538290&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
Atorvastatin stent coating does not reduce neointimal proliferation after coronary stenting.

Scheller B, Schmitt A, Bohm M, Nickenig G.

University of Saarland Internal Medicine III, 66421 Homburg/Saar, Germany. bruno.scheller uniklinik-saarland.de

PURPOSE: Statins seem to be suitable for restenosis prevention via reduction of smooth muscle cell proliferation, anti-inflammatory effects, and improvement of endothelial function. The aim of the present study was to test the efficacy of an atorvastatin stent coating for restenosis inhibition in the porcine coronary stent model. METHODS AND RESULTS: Twenty stents (BiodivYsio Matrix LO, uncoated or with 56 microg atorvastatin load) were implanted in LAD and CX coronary arteries of 10 domestic pigs with an over stretch ratio of 1.25. Quantitative angiography and histomorphometry of the stented arteries asserted statistic equality of the baseline parameters between the control and treatment group. After 28 days, there was no significant difference in parameters describing in-stent restenosis (neointimal area 3.14 +/- 1.13 mm(2) [control] vs. 3.12 +/- 1.07 mm(2) [atorvastatin stent]; p = 0.978). However, there was a trend towards a lower degree of inflammation in the atorvastatin stent group. CONCLUSION: Atorvastatin stent coating showed a trend towards reduced local inflammation near the stent struts, but could not reduce neointimal formation in the porcine coronary over stretch model.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14663613&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
Atorvastatin reduction of intravascular thrombosis, increase in cerebral microvascular patency and integrity, and enhancement of spatial learning in rats subjected to traumatic brain injury.

Lu D, Mahmood A, Goussev A, Schallert T, Qu C, Zhang ZG, Li Y, Lu M, Chopp M.

Department of Neurosurgery, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA.

OBJECT: Atorvastatin, a beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor, has pleiotropic effects, such as promoting angiogenesis, increasing fibrinolysis, and reducing inflammatory responses, and has shown promise in enhancing recovery in animals with traumatic brain injury (TBI) and stroke. The authors tested the effect of atorvastatin on vascular changes after TBI. METHODS: Male Wistar rats subjected to controlled cortical impact injury were perfused at different time points with fluorescein isothiocyanate (FITC)--conjugated dextran 1 minute before being killed. Spatial memory function had been measured using a Morris Water Maze test at various points before and after TBI. The temporal profile of intravascular thrombosis and vascular changes was measured on brain tissue sections by using a microcomputer imaging device and a laser confocal microscopy. The study revealed the following results. 1) Vessels in the lesion boundary zone and hippocampal CA3 region showed a variety of damage, morphological alterations, reduced perfusion, and intraluminal microthrombin formation. 2) Atorvastatin enhanced FITC-dextran perfusion of vessels and reduced intravascular coagulation. 3) Atorvastatin promoted the restoration of spatial memory function. CONCLUSIONS. These results indicated that atorvastatin warrants investigation as a potential therapeutic drug for TBI.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15540920&dopt=Abstract atorvastatin Lipitor