Atorvastatin – ABC CARDIOL

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Original Article

The Effect of Atorvastatin + Aspirin on the Endothelial Function Differs with Age in Patients with HIV: A Case-Control Study

Gerson Gomes dos Santos Junior et al. Paulo Sérgio Ramos Araújo Kaliene Maria Estevão Leite Emmanuelle Tenório Godoi … Adriana Ferraz Vasconcelos Heloisa Ramos Lacerda

Abstract

Background

Patients with HIV are more likely to present with cardiovascular disease when compared to the general population.

Objective

This was a case-control study that aimed to assess which factors were associated with a reduction in the carotid intima-media thickness (IMT) and an increase in the brachial artery flow-mediated dilation (FMD) in HIV patients who received atorvastatin + aspirin during a period of 6 months.

Methods

A secondary analysis of a clinical trial was conducted, which included people living with HIV infection and low cardiovascular risk. A total of 38 patients allocated to the intervention arm and treated for 6 months with a combination of atorvastatin + aspirin were included. All participants underwent a carotid and brachial artery ultrasound, both at the beginning and the end of the study. Cases that responded with an increase of >10% of the brachial dilatation (FMD) and reduction of the carotid intima-media thickness (IMT) were considered cases, and those who did not respond were considered controls. We assessed the factors associated with the positive responses obtained through IMT and FMD.

Results

A reduction in the IMT was not significantly associated with any of the evaluated risk factors: age (p=0.211), gender (p=0.260), smoking (p=0.131) or time since HIV diagnosis (p=0.836). An increase in the FMD was significantly associated with age amongst those in the 40-59 age group, p = 0.015 (OR = 4.37; 95% CI: 1.07-17.79).

Conclusions

Older individuals were more likely to present with an increased FMD after 6 months of treatment with atorvastatin + aspirin.

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Original Article

Atorvastatin Attenuates Vascular Remodeling in Mice with Metabolic Syndrome

Karine Ferreira da Silva Carvalho et al. Amanda Araújo Marques Ferreira Nayara Carvalho Barbosa Juliano Vilela Alves Rafael Menezes da Costa

Abstract

Background

Metabolic syndrome is characterized by an array of comorbidities. During this syndrome, structural changes are observed in the cardiovascular system, especially vascular remodeling. One of the predisposing causes for these changes is chronic inflammation resulting from changes in the structure and composition of perivascular adipose tissue. Atorvastatin is effective in the treatment of dyslipidemias. However, its pleiotropic effects have not been completely understood. We hypothesize that metabolic syndrome may lead to vascular remodeling and that atorvastatin therapy may be able to attenuate this condition.

Objectives

To assess the effects of atorvastatin therapy on vascular remodeling in an experimental model of metabolic syndrome.

Methods

Swiss mice received a control diet or a hyperglicemic diet for 18 weeks. After 14 weeks of diet, mice were treated with vehicle or atorvastatin (20mg/kg) during for 4 weeks. Nutritional and metabolic profiles were assessed by biochemical tests; moreover, a histological assessment of aorta structure was conducted, and cytokine levels were determined by the immunoenzyme assay. The acceptable level of significance for the results was set at p<0.05.

Results

Hyperglicemic diet promoted the development of metabolic syndrome. It indeed culminated in hypertrophic remodeling of vascular smooth muscle and perivascular adipose tissue. Furthermore, there were increases in the levels of circulating TNF-α and IL-6 and in the perivascular adipose tissue. Atorvastatin therapy significantly reduced metabolic damages, vascular remodeling, and cytokine levels.

Conclusion

Atorvastatin attenuate metabolic damages associated with metabolic syndrome induced by hyperglycemic diet, in addition to attenuating vascular remodeling; both effects are associated with reduced levels of pro-inflammatory cytokines.

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Original Article

Atorvastatin Reduces Accumulation of Vascular Smooth Muscle Cells to Inhibit Intimal Hyperplasia via p38 MAPK Pathway Inhibition in a Rat Model of Vein Graft

Tianshu Chu et al. Molin Huang Zhiwei Zhao Fei Ling … Jing Cao Jianjun Ge

Abstract

Background:

The rate of saphenous vein graft failure one year after coronary artery bypass grafting ranges from 10% to 25%. The aim of this study was to explore whether atorvastatin can reduce accumulation of vascular smooth muscle cells to inhibit intimal hyperplasia via p38 MAPK pathway inhibition.

Methods:

Forty-five Sprague-Dawley rats were randomized to three groups. Thirty rats received a vein graft operation, and they were randomized to be treated with vehicle or atorvastatin; fifteen rats received a sham operation. We detected intimal hyperplasia by hematoxylin-eosin staining and related protein expression by immunohistochemical and Western blot analysis. Comparisons were analyzed by single-factor analysis of variance and Fisher’s least significant difference test, with p < 0.05 considered significant.

Results:

The intima analyzed by hematoxylin-eosin staining was dramatically thicker in the control group than in the atorvastatin group and sham group (p < 0.01). The outcomes of immunohistochemical staining of α-SMA demonstrated that the percentage of α-SMA-positive cells in the control group was higher than in the atorvastatin group (p < 0.01). We also evaluated α-SMA, PCNA, p38 MAPK, and phosphorylation of p38 MAPK after statin treatment by Western blot analysis, and the results indicated that atorvastatin did not lead to p38 MAPK reduction (p < 0.05); it did, however, result in inhibition of p38 MAPK phosphorylation (p < 0.01), and it significantly reduced α-SMA and PCNA levels, in comparison with the control group (p < 0.01).

Conclusion:

We have demonstrated that atorvastatin can inhibit accumulation of vascular smooth muscle cells by inhibiting the p38 MAPK pathway, and it is capable of inhibiting intimal hyperplasia in a rat vein graft model.

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Original Article

Evaluation of Sexual Dimorphism in the Efficacy and Safety of Simvastatin/Atorvastatin Therapy in a Southern Brazilian Cohort

Lisiane Smiderle et al. Luciana O. Lima Mara Helena Hutz Cézar Roberto Van der Sand … Luiz Carlos Van der Sand Maria Elvira Wagner Ferreira Renan Canibal Pires Silvana Almeida Marilu Fiegenbaum

Background:

Dyslipidemia is the primary risk factor for cardiovascular disease, and statins have been effective in controlling lipid levels. Sex differences in the pharmacokinetics and pharmacodynamics of statins contribute to interindividual variations in drug efficacy and toxicity.

Objective:

To evaluate the presence of sexual dimorphism in the efficacy and safety of simvastatin/atorvastatin treatment.

Methods:

Lipid levels of 495 patients (331 women and 164 men) were measured at baseline and after 6 ± 3 months of simvastatin/atorvastatin treatment to assess the efficacy and safety profiles of both drugs.

Results:

Women had higher baseline levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) compared with men (p < 0.0001). After treatment, women exhibited a greater decrease in plasma TC and LDL-C levels compared with men. After adjustment for covariates, baseline levels of TC and LDL-C influenced more than 30% of the efficacy of lipid-lowering therapy (p < 0.001), regardless of sex. Myalgia [with or without changes in creatine phosphokinase (CPK) levels] occurred more frequently in women (25.9%; p = 0.002), whereas an increase in CPK and/or abnormal liver function was more frequent in in men (17.9%; p = 0.017).

Conclusions:

Our results show that baseline TC and LDL-C levels are the main predictors of simvastatin/atorvastatin therapy efficacy, regardless of sex. In addition, they suggest the presence of sexual dimorphism in the safety of simvastatin/atorvastatin. The effect of sex differences on receptors, transporter proteins, and gene expression pathways needs to be better evaluated and characterized to confirm these observations.

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Artigo Original

Efficacy of atorvastatin when not administered daily

Antonio Edmond Ghattas et al. João Pimenta

BACKGROUND: Statins are widely used because they reduce cardiac events. Although they are indicated for daily use, some doctorsgive prescriptions for every other day, mainly with the purpose of reducing costs. OBJECTIVE: To evaluate the efficacy of atorvastatin, when not administered everyday, on LDL-cholesterol (LDL-C) levels, and also to evaluate cost reduction. METHODS: A total of 100 patients with hypercholesterolemia in primary (PP) and secondary prevention (SP) were assessed. After a 12-week diet period, atorvastatin was initiated at a dose of 10 mg per day. After six weeks, LDL-C was determined, and if the levels were <80 or <104 mg/dL for SP and PP, respectively, two atorvastatin doses were subtracted per week. If LDL-C remained <80 or <104 mg/dL, a further reduction to three times a week was allowed, and the last determination was performed after six more weeks. The percentage variation in costs was the parameter to evaluate the saving. RESULTS: In 47 out of the 52 patients of this group, a reduction by 32% in LDL-C was observed, and daily atorvastatin was maintained. Forty one patients remained throughout the study and had their weekly dosage reduced. In 25 patients the medication was administered three times a week, and in 16, five times a week, with reductions of 42.4% and 46.1% in LDL-C, respectively. As regards costs, one of the groups had their monthly expense reduced from R$ 106.65 to R$ 74.65, and the other group from R$ 106.65 to R$ 53.33. CONCLUSION: The results suggest that atorvastatin may be administered on a non-daily basis. A cost reduction between 30% and 50% was also observed.

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