atorvastatin Lipitor
Atorvastatin reduces proinflammatory markers in hypercholesterolemic patients.

Ascer E, Bertolami MC, Venturinelli ML, Buccheri V, Souza J, Nicolau JC, Ramires JA, Serrano CV Jr.

Heart Institute (InCor HCFMUSP), Medical School, University of Sao Paulo, Fundacao Maria Cecilia Souto Vidigal, Av. Eneas de C. Aguiar 44, Sao Paulo, SP 05403-901, Brazil. dclascer incor.usp.br

BACKGROUND: Reduction in cardiovascular events with statins has been in part attributed to their anti-inflammatory properties. OBJECTIVE: Evaluate the effects of atorvastatin on levels of inflammatory markers, such as tumor necrosis factor-alpha (TNF), interleukins (IL-1 and IL-6), soluble intercellular adhesion molecule-1 (sICAM-1) and C-reactive protein (CRP) in hypercholesterolemic patients (LDL-cholesterol >160 mg/dL). METHODS AND RESULTS: Two lipid-lowering regimens were taken for 8 weeks. One set of patients (n=45, 26 men, average 50 +/- 2 years of age) was subjected to atorvastatin treatment (20-40 mg/day), plus diet recommendation. Another set of patients (n=23, 12 men, average 53 +/- 3 years of age) went through diet recommendation alone. Both groups were recommended to perform standard physical activity. Plasma samples were collected after overnight fasting at baseline and after 8 weeks for ELISA. The use of atorvastatin when compared to diet alone, resulted in significant (P <0.0001) reductions for: LDL-cholesterol (39.9% versus 4.4%), TNF (21.4% versus 2.9%), IL-6 (22.1% versus 2.0%), IL-1 (16.4% versus 2.7%) and sICAM-1 (9.6% versus 0.1%), respectively. The percentage of patients with CRP levels >3 mg/dL in the atorvastatin group fell from 25.0 to 6.7% (P <0.0001) while in the diet group the reduction was not significant. CONCLUSION: In hypercholesterolemic patients, atorvastatin, compared to diet alone resulted in significant reductions in levels of proinflammatory cytokines (TNF, IL-1 and IL-6) as well as in sICAM-1 and CRP. Thus, statin-induced inhibition of inflammatory markers may play an important role in the pharmacological and clinical effects of statins seen in cardiovascular diseases.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15488879&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
Atorvastatin effect on high-density lipoprotein-associated paraoxonase activity and oxidative DNA damage.

Harangi M, Seres I, Varga Z, Emri G, Szilvassy Z, Paragh G, Remenyik E.

1st Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.

OBJECTIVE: High-density lipoprotein (HDL)-associated antioxidant paraoxonase (PON) may reduce low-density lipoprotein (LDL) oxidation and prevent atherosclerosis. The aim of this present study was to investigate the effect of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor atorvastatin on hydrogen-peroxide-induced DNA damage by comet assay and the correlation between oxidative DNA damage and antioxidant PON activity. METHODS: Thirteen type-II/a hyperlipidemic patients were enrolled in the study. We examined the effect of 10 mg/day atorvastatin treatment on lipid levels and the degree of DNA damage in lymphocytes separated from hyperlipidemic patients, nitric oxide (NO), thiobarbituric acid-reactive substances (TBARS), PON levels and activity. RESULTS: After 6 months, atorvastatin treatment significantly decreased serum cholesterol and LDL-cholesterol levels. The triglyceride level did not change, and there was no significant change in the HDL cholesterol level. The visual score characteristic to the degree of DNA damage in comet assay was significantly decreased, as well as the TBARS level, while the level of NO was non-significantly increased. PON activity and the PON/HDL ratio were significantly increased after atorvastatin treatment. There was a negative correlation between DNA damage and PON activity, as well as between DNA damage and the PON/HDL ratio before and after atorvastatin treatment. CONCLUSION: These findings show that atorvastatin treatment favorably affected the lipid profile, increasing the activity of HDL-associated PON and decreasing the cytotoxic effect of oxidative stress.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15490140&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
Effect of low dose atorvastatin versus diet-induced cholesterol lowering on atherosclerotic lesion progression and inflammation in apolipoprotein E*3-Leiden transgenic mice.

Verschuren L, Kleemann R, Offerman EH, Szalai AJ, Emeis SJ, Princen HM, Kooistra T.

Gaubius Laboratory, TNO-Prevention and Health, Leiden, The Netherlands.

OBJECTIVE: To evaluate whether low-dose atorvastatin suppresses atherosclerotic lesion progression and inflammation in apolipoprotein E*3 (apoE*3)-Leiden mice beyond its cholesterol-lowering effect. METHODS AND RESULTS: ApoE*3-Leiden mice were fed a high-cholesterol (HC) diet until mild atherosclerotic lesions had formed. Subsequently, HC diet feeding was continued or mice received HC supplemented with 0.002% (w/w) atorvastatin (HC+A), resulting in 19% plasma cholesterol lowering, or mice received a low-cholesterol (LC) diet to establish a plasma cholesterol level similar to that achieved in the HC+A group. HC+A and LC diet reduced, significantly and to the same extent, lesion progression and complication in the aortic root, as assessed by measuring total atherosclerotic lesion area, lesion severity, and macrophage and smooth muscle cell area. In the aortic arch, HC+A but not LC blocked lesion progression. HC+A and LC reduced vascular inflammation (ie, expression of macrophage migration inhibitory factor , plasminogen activator inhibitor- 1, matrix metalloproteinase-9), but HC+A additionally suppressed vascular cell adhesion molecule-1 expression and, in parallel, monocyte adhesion. In contrast, low-dose atorvastatin showed no antiinflammatory action toward hepatic inflammation markers (serum amyloid A, C-reactive protein [CRP]) in apoE*3-Leiden mice and human CRP transgenic mice. CONCLUSIONS: Low-dose atorvastatin cholesterol-dependently reduces lesion progression in the aortic root but shows antiinflammatory vascular activity and tends to retard atherogenesis in the aortic arch beyond its cholesterol-lowering effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15514207&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
Effect of atorvastatin on non-cholesterol sterols in patients with type 2 diabetes mellitus and cardiovascular disease.

Smahelova A, Hyspler R, Haas T, Ticha A, Blaha V, Zadak Z.

Department of Metabolic Care and Gerontology, University Hospital, Charles University, Sokolska 581, 50005 Hradec Kralove, Czech Republic. smahelov lfhk.cuni.cz

An increased risk of cardiovascular morbidity and mortality in diabetes mellitus type 2 has been associated with disturbances of lipid homeostasis. Recently, decreased intestinal absorption of cholesterol and increased liver cholesterol production have been reported. To investigate the influence of cholesterol lowering therapy using statin on cholesterol turnover in diabetes mellitus type 2, the levels of non-cholesterol based sterols were studied. One hundred and thirty five patients with type 2 diabetes and non-diabetic controls with cardiovascular diseases were studied. Both groups were divided into two subgroups: treated with atorvastatin and without statin therapy. The diabetics showed significantly higher levels of lathosterol (6.97micromol l(-1) versus 5.11micromol l(-1), p = 0.012) and lower levels of sitosterol (5.03micromol l(-1) versus 8.98micromol l(-1), p < 0.001) and campesterol (6.35micromol l(-1) versus 9.80micromol l(-1), p < 0.001). Non-diabetics showed no significant differences in non-cholesterol based sterols in relation to atorvastatin therapy. A significantly lower level of lathosterol as well as a decrease in lathosterol/cholesterol ratio in the statin treated groups was found in diabetics (4.11micromol l(-1) versus 7.83micromol l(-1), p < 0.001). The results based on ANOVA analysis show that the effect of atorvastatin on the lathosterol level is more pronounced in diabetics. Regression analysis showed the relationship between increased triglycerides levels and the increase in cholesterol synthesis. The calculated regression model for loglathosterol in diabetics has the following form: log(lathosterol) = 2.76 - 0.52.statin + 0.22.cholesterol (ANOVA, p < 0.001, R(2) = 34%, p = 0.005 for statin, p < 0.001 for cholesterol). We conclude that in spite the total cholesterol level in diabetics type 2 is not increased, its endogenous synthesis is enhanced. Our results show that the diabetics type 2 with increased serum lathosterol and expressed metabolic syndrome (mild increase of triglycerides) might represent a suitable group for intensive treatment with statins.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15519532&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
Antiplatelet effects of a 600 mg loading dose of clopidogrel are not attenuated in patients receiving atorvastatin or simvastatin for at least 4 weeks prior to coronary artery stenting.

Gorchakova O, von Beckerath N, Gawaz M, Mocz A, Joost A, Schomig A, Kastrati A.

Medizinische Klinik rechts der Isar, Technische Universitat Munchen, Munich, Germany.

AIMS: To test prospectively whether the antiplatelet effect of a 600 mg loading dose of clopidogrel is attenuated in patients receiving atorvastatin and simvastatin for at least 4 weeks prior to coronary artery stenting. METHODS AND RESULTS: Blood samples were obtained at least 2 h after receiving 100 mg aspirin and 600 mg clopidogrel and prior to coronary stenting from 90 patients without statin therapy and 90 patients with statin (atorvastatin and simvastatin) therapy for at least 4 weeks. Maximal and residual platelet aggregation was evaluated with optical aggregometry in response to ADP (5 and 20 micromol/l). Surface expression of IIb/IIIa (CD61) and P-selectin (CD62) was assessed with whole blood flow-cytometry at baseline and following stimulation (5 and 20 micromol/l ADP). Inhibition of ADP-induced platelet aggregation was not impaired in the presence of concomitant statin therapy. Moreover, patients with and without statin therapy did not differ in respect to all flow-cytometric parameters obtained. CONCLUSION: The antiplatelet effect of a high, 600 mg loading dose of clopidogrel is not diminished in patients receiving atorvastatin and simvastatin for at least 4 weeks prior to coronary stenting.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15522468&dopt=Abstract atorvastatin Lipitor



atorvastatin Lipitor
Increased levels of pregnancy-associated plasma protein-A in patients with hypercholesterolemia: the effect of atorvastatin treatment.

Stulc T, Malbohan I, Malik J, Fialova L, Soukupova J, Ceska R.

Third Department of Internal Medicine, Charles University, Prague, Czech Republic. TSTULC LF1.CUNI.CZ

BACKGROUND: Serum levels of pregnancy-associated plasma protein-A (PAPP-A) have recently been linked to plaque instability and are increased in acute coronary syndromes. The relation between PAPP-A levels and coronary risk factors, namely blood lipids, has not been studied to date. We have therefore investigated whether serum PAPP-A levels are increased in asymptomatic hypercholesterolemic subjects and whether PAPP-A levels are influenced by atorvastatin therapy. METHODS: We examined 27 subjects with isolated hypercholesterolemia free of manifest vascular disease and 29 age-matched healthy control subjects. Patients were examined at baseline and after 10 weeks of atorvastatin treatment (20 mg/d). RESULTS: In untreated hypercholesterolemic subjects, PAPP-A levels were significantly higher than in control subjects (8.02 +/- 1.86 mU/L vs 6.50 +/- 2.54 mU/L, P =.018). There was no correlation between PAPP-A levels and serum lipid levels. Atorvastatin treatment reduced total and LDL-cholesterol by 31% and 40%, respectively. Despite this profound lipid lowering, there was no significant change in the serum PAPP-A levels. CONCLUSIONS: PAPP-A levels are elevated in hypercholesterolemic subjects without clinical signs of atherosclerosis. PAPP-A may therefore not only reflect plaque instability but also serve as a marker of total atherosclerotic burden in asymptomatic subjects with hyperlipidemia. However, PAPP-A levels are not influenced by atorvastatin treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14661010&dopt=Abstract atorvastatin Lipitor