No effects of atorvastatin (10mg/d or 80mg/d) on nitric oxide, prostacyclin, thromboxane and oxidative stress in type 2 diabetes mellitus patients of the DALI study

Tsikas, Dimitrios; Pham, Vu Vi; Suchy, Maria-Theresia; Ree, Marcel A. van de; Huisman, Menno V.; Frölich, Jürgen C.; Princen, H.M.G.

doi:10.1016/j.phrs.2015.01.004

Cited by 12 publications

(6 citation statements)

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“…In our study, after intervention with atorvastatin, the total cholesterol and LDL-C levels were decreased specially in group B. It has been well recognized that statins decrease plasma LDL-C and cholesterol levels by inhibition of HMG-CoA reductase (9). Additionally, both doses of atorvastatin lowered TGs levels.…”

Section: Discussionsupporting

confidence: 53%

“…However, lipidlowering drugs especially statins (inhibitors of 3-hydroxy-3-methylglutaryl-CoA [HMG-CoA] reductase the main enzyme in the synthesis of cholesterol) are one of the most widely used therapies in different groups of patients not only because of cholesterol-lowering properties but also due to their ''pleiotropic mechanisms'' (8). The reduction in vascular inflammation and oxidative stress and improvement in atherosclerotic plaque stability, are some examples of statins pleiotropic effects (9). More recently, intensive lipid lowering with higher statin doses over regularly used doses have gained more attention because they might have significant therapeutic benefits (10).…”

Section: Key Pointmentioning

confidence: 99%

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Effect of high dose versus low dose of atorvastatin therapy on inflammation and coagulation factors in type 2 diabetic patients; a randomized clinical trial study

Niafar¹,

Bahrami²,

Yagin³

et al. 2019

Immunopathol Persa

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Introduction: Statins are one of the most widely used therapies in different groups of patients not only because of cholesterol-lowering properties but also due to their non-lipid related mechanisms. However, the effects of atorvastatin on inflammatory and coagulation markers in type 2 diabetic patients are not well examined. Objectives: To evaluate, the effects of two different doses of atorvastatin on lipid profile, inflammatory coagulation markers, and liver enzymes in type 2 diabetic patients. Patients and Methods: In a randomized double-blinded controlled trial, 150 diabetic patients were randomly assigned to get atorvastatin 10 mg/d (n = 74) or 40 mg/d (n = 76) for 12 weeks. The concentration of biomarkers was determined both at the onset of the study as well as at the completing time of the intervention. Results: Significant differences between the mean levels of lipid profiles, fibrinogen, interleukin-1 (IL-1) and IL-6 were observed between two groups after three months treatment with atorvastatin 10 and 40 mg/d (P < 0.05). Furthermore, significant improvement in all blood values after atorvastatin 40 mg/d ingestion was observed (P < 0.05) except for homocysteine and creatine phosphokinase (CPK) levels (P > 0.05). Conclusion: Atorvastatin therapy especially with higher dose was associated with inflammation and coagulation parameters improvement in diabetic individuals. Trial Registration: Registration of randomized double-blinded clinical trial has been approved in Iranian registry of clinical trial (identifier: IRCT201502226710N5;

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Section: Discussionsupporting

confidence: 53%

Section: Key Pointmentioning

confidence: 99%

Effect of high dose versus low dose of atorvastatin therapy on inflammation and coagulation factors in type 2 diabetic patients; a randomized clinical trial study

Niafar¹,

Bahrami²,

Yagin³

et al. 2019

Immunopathol Persa

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“…We have previously shown that rosuvastatin decreases monocyte activation [soluble CD14 and the proportion of tissue factor-expressing patrolling monocytes (CD14dimCD16+ cells)], T-cell activation (proportion of CD38+HLA-DR+ T cells), systemic inflammation [cystatin C and interferon γ inducible protein-10 (IP-10)] and vascular inflammation (lipoprotein-associated phospholipase A2) in HIV [20–23]. Statins have antioxidant activity [24,25] and decrease markers of oxidative stress in some [26–28], but not all [29,30] disease states. To our knowledge, the effect of statins on oxLDL or other oxidative stress markers in the setting of chronic HIV infection has not been studied.…”

Section: Introductionmentioning

confidence: 99%

Changes in oxidized lipids drive the improvement in monocyte activation and vascular disease after statin therapy in HIV

Hileman

Turner

Funderburg

et al. 2016

Aids

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Background Oxidative stress plays a significant role in atherosclerosis development. HIV infection has been linked with heightened cardiovascular disease risk. HMG-CoA reductase inhibitors may reduce oxidative stress and subsequently subclinical vascular disease in HIV. Design/methods This is a randomized, placebo-controlled trial to evaluate the effect of rosuvastatin in HIV-infected adults on stable antiretroviral therapy with low-density lipoprotein less than 130 mg/dl and increased inflammation or T-cell activation on subclinical vascular disease. Changes over 48 weeks in oxidative stress markers, oxidized low-density lipoprotein (oxLDL) and F2-isoprostane/creatinine ratio (F2-Iso-P/Cr), were compared between groups. Spearman correlation and multivariable linear regression were used to evaluate relationships between changes in markers of oxidative stress, inflammation and monocyte activation and carotid intima media thickness (CIMT). Results One hundred and forty-seven adults enrolled (72 to rosuvastatin and 75 to placebo). In the rosuvastatin group, oxLDL decreased significantly over 24 weeks compared to placebo [mean absolute change in log-oxLDL for rosuvastatin −0.2 ± 0.468 log U/l (P < 0.001 within-group) vs. placebo −0.018 ± 0.456 log U/l (P = 0.83 within-group); P = 0.004 between groups] and this change was linked with changes in soluble CD14 and proportion of patrolling monocytes (CD14dimCD16+). Although oxLDL levels increased after initially declining and were not different from placebo at week 48, the early improvement in oxLDL was associated with improved CIMT at week 48. Changes in F2-IsoP/Cr were not significant between groups. Conclusion Rosuvastatin decreases oxLDL levels early after initiation and is associated with decreased monocyte activation. Early improvement in oxLDL is linked with improved CIMT in treated HIV infection.

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“…In addition, GFR improved after a four-week therapy with 40 mg simvastatin per day in patients with autosomal dominant polycystic kidney disease, which was associated with improved endothelium-dependent dilation in the forearm [ 27 ]. On the other hand, in subjects with type 2 diabetes, administration of atorvastatin (10 or 80 mg/day) for 30 weeks neither improved impaired flow-mediated dilation of the brachial artery [ 28 ] nor affected urinary markers of systemic NO generation and oxidative stress [ 29 ] as compared to patients randomized to placebo.…”

Section: Discussionmentioning

confidence: 99%

Effects of Atorvastatin Dose and Concomitant Use of Angiotensin-Converting Enzyme Inhibitors on Renal Function Changes over Time in Patients with Stable Coronary Artery Disease: A Prospective Observational Study

Wieczorek-Surdacka

Świerszcz

Surdacki

2016

IJMS

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Angiotensin-converting enzyme inhibitors (ACEI) and statins are widely used in patients with coronary artery disease (CAD). Our aim was to compare changes in glomerular filtration rate (GFR) over time in subjects with stable CAD according to atorvastatin dose and concomitant use of ACEI. We studied 78 men with stable CAD referred for an elective coronary angiography who attained the then-current guideline-recommended target level of low-density lipoproteins (LDL) cholesterol below 2.5 mmol/L in a routine fasting lipid panel on admission and were receiving atorvastatin at a daily dose of 10–40 mg for ≥3 months preceding the index hospitalization. Due to an observational study design, atorvastatin dosage was not intentionally modified for other reasons. GFR was estimated during index hospitalization and at about one year after discharge from our center. Irrespective of ACEI use, a prevention of kidney function loss was observed only in those treated with the highest atorvastatin dose. In 38 subjects on ACEI, both of the higher atorvastatin doses were associated with increasing beneficial effects on GFR changes (mean ± SEM: −4.2 ± 2.4, 1.1 ± 1.6, 5.2 ± 2.4 mL/min per 1.73 m2 for the 10-mg, 20-mg and 40-mg atorvastatin group, respectively, p = 0.02 by ANOVA; Spearman’s rho = 0.50, p = 0.001 for trend). In sharp contrast, in 40 patients without ACEI, no significant trend effect was observed across increasing atorvastatin dosage (respective GFR changes: −1.3 ± 1.0, −4.7 ± 2.1, 4.8 ± 3.6 mL/min per 1.73 m2, p = 0.02 by ANOVA; rho = 0.08, p = 0.6 for trend). The results were substantially unchanged after adjustment for baseline GFR or time-dependent variations of LDL cholesterol. Thus, concomitant ACEI use appears to facilitate the ability of increasing atorvastatin doses to beneficially modulate time-dependent changes in GFR in men with stable CAD.

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No effects of atorvastatin (10mg/d or 80mg/d) on nitric oxide, prostacyclin, thromboxane and oxidative stress in type 2 diabetes mellitus patients of the DALI study

Cited by 12 publications

References 82 publications

Effect of high dose versus low dose of atorvastatin therapy on inflammation and coagulation factors in type 2 diabetic patients; a randomized clinical trial study

Effect of high dose versus low dose of atorvastatin therapy on inflammation and coagulation factors in type 2 diabetic patients; a randomized clinical trial study

Changes in oxidized lipids drive the improvement in monocyte activation and vascular disease after statin therapy in HIV

Effects of Atorvastatin Dose and Concomitant Use of Angiotensin-Converting Enzyme Inhibitors on Renal Function Changes over Time in Patients with Stable Coronary Artery Disease: A Prospective Observational Study

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