High-dose atorvastatin treatment in patients with peripheral arterial disease: Effects on platelet aggregation, blood rheology and plasma homocysteine

Loo, Bernd van der; Spring, Silviana; Koppensteiner, Renate

doi:10.3233/ch-2011-1386

Cited by 24 publications

(7 citation statements)

References 34 publications

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“…Consistently, metaregression analyses suggested a marginally significant positive dose-response trend between the percent use of lipid-lowering drugs and log-RR, and a marginally significant inverse dose-response trend between percent baseline hypertension and log-RR for total cancer incidence risk associated with folic acid supplementation. A recent study 32 reported an increase in homocysteine levels in the presence of rather elevated levels of folic acid after high-dose atorvastatin treatment, which suggests that statins treatment may play an important role in the homocysteine metabolic cycle and may possibly affect cancer risk associated with folic acid supplementation. Higher total folate intake was associated with a decreased risk of incident hypertension.…”

Section: Discussionmentioning

confidence: 98%

Folic acid supplementation and cancer risk: A meta‐analysis of randomized controlled trials

Qin

Chen

Shen

et al. 2013

Intl Journal of Cancer

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There are growing data and a continuing controversy over the effect of folic acid supplementation on cancer risk. We conducted a meta-analysis based on up-to-date published relevant randomized trials to further examine this issue. Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of cancer using a random-effects model. Overall, folic acid supplementation had no significant effect on total cancer incidence (13 trials, n 5 49,406, RR 5 1.05; 95% CI: 0.99-1.11, p 5 0.13), colorectal cancer (seven trials, n 5 33,824, 1.01; 0.82-1.23, p 5 0.95), other gastrointestinal cancer (two trials, n 5 20,228, 1.00; 0.75-1.33, p 5 0.99), prostate cancer (five trials, n 5 27,065, 1.17; 0.84-1.62, p 5 0.35), other genitourinary cancer (two trials, n 5 20,228, 0.97; 0.75-1.27, p 5 0.84), lung cancer (five trials, n 5 31,864, 1.00; 0.84-1.21, p 5 0.97), breast cancer (four trials, n 5 19,800, 0.82; 0.63-1.07, p 5 0.15), hematological malignancy (three trials, n 5 25,670, 0.87; 0.64-1.17, p 5 0.35) and total cancer mortality (six trials, n 5 31,930, 1.02; 0.90-1.15, p 5 0.81). However, a significantly reduced risk was observed for melanoma (three trials, n 5 19,128, 0.47; 0.23-0.94, p 5 0.03). Furthermore, higher total cancer incidence risk was observed among those trials with a higher percent use of lipid-lowering drugs (>60%, 1.10; 1.00-1.20, p 5 0.04), or with lower percent baseline hypertension (70%, 1.08; 1.00-1.16, p 5 0.057).Consistently, meta-regression analyses suggested that the similar trend between percent use of lipid-lowering drugs (p 5 0.084) or percent baseline hypertension (p 5 0.056) and log-RR for total cancer incidence associated with folic acid supplementation. Our findings indicate that folic acid supplementation has no significant effect on total cancer incidence, colorectal cancer, prostate cancer, lung cancer, breast cancer or hematological malignancy, but reduces the risk of melanoma.There is general consensus that folic acid supplementation during the periconceptional period is effective in reducing neural tube defects.1 Furthermore, our previous meta-analysis reported that folic acid supplementation could significantly reduce the risk of stroke, 2,3 the risk of cardiovascular disease in patients with end-stage renal disease or advanced chronic kidney disease 4 and the progression of carotid intima-media thickness.5 However, folic acid supplementation, particularly the population-based exposure to folic acid through fortification, remains controversial due to concerns about potential adverse effects on health. The most important concern is that folic acid supplementation could increase the risk of cancer. 6A previous meta-analysis of eight randomized controlled trials (RCTs) of folic acid supplementation involving 35,603 individuals at increased risk of cardiovascular disease did not find any significant adverse effect of folic acid on cancer incidence overall or cancer mortality for a median duration of 5 years.7 A recent meta-analysis of 10 RCTs (n 5 38,233), however...

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Section: Discussionmentioning

confidence: 98%

Folic acid supplementation and cancer risk: A meta‐analysis of randomized controlled trials

Qin

Chen

Shen

et al. 2013

Intl Journal of Cancer

View full text Add to dashboard Cite

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“…Also, in another study carried out by Navarro et al, serum Hcy levels did not alter significantly in diabetic patients on hemodialysis, despite improvement in lipid profile and hsCRP levels by atorvastatin administration (31). However, Van der Loo et al, revealed that administration of 80 mg/d of atorvastatin led to an increase in Hcy plasma levels in patients with peripheral arterial disease (33). The contradictories in different studies can be partly due to the dose of statins, the intervention duration, different types of diseases and patients' metabolic profiles.…”

Section: Discussionmentioning

confidence: 91%

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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“…Of note, Van der Loo et al showed that treatment with 80 mg atorvastatin resulted in an increase of homocysteine plasma levels in the presence of rather elevated levels of folic acid among patients with peripheral arterial disease ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

The association between atorvastatin administration and plasma total homocysteine levels in renal transplant recipients

Monfared¹,

Azimi²,

Kazemnezhad³

2016

J Nephropathol

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Background Statins improve prognosis in patients with coronary heart diseases by decreasing the incidence of vascular events. Excess prevalence of hyperhomocysteinemia, an independent risk factor of cardiovascular diseases, has been observed in stable renal transplant recipients (RTRs). Objectives The objective of our study was to evaluate the association between atorvastatin administration and plasma total homocysteine (tHcy) levels in RTRs. Patients and Methods We performed a retrospective cross-sectional study in 148 cyclosporine A (CsA) treated stable RTRs. We compared tHcy level and other demographic and clinical variables in RTRs with and without atorvastatin. Results 58.1% of the 148 RTRs were treated with atorvastatin (20-40 mg/day). Mean tHcy levels were lower in patients treated with atorvastatin compared to nonusers (14.80 ± 5.13 µmol/l versus 16.95 ± 7.87 µmol/l, P = 0.04). The comparison of 85 patients treated with atorvastatin and 61 non-users revealed that those subjects with atorvastatin were older, with higher estimated creatinine clearance and elevated body mass index (BMI). They were more likely to have higher systolic blood pressure and CsA trough level (C0). The association between lower tHcy levels and atorvastatin use was confirmed in the multivariate regression model (P = 0.004). However tHcy levels were independently and negatively associated with serum folate (P = 0.0001) and vitamin B12 levels (P = 0.001) and positively with serum BUN (P = 0.001) and diastolic blood pressure (P = 0.024) as well. Conclusions These data support the association between lower tHcy levels and atorvastatin administration in RTRs. Further clinical trials are recommended to clarify homocysteine lowering effect of atorvastatin.

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High-dose atorvastatin treatment in patients with peripheral arterial disease: Effects on platelet aggregation, blood rheology and plasma homocysteine

Cited by 24 publications

References 34 publications

Folic acid supplementation and cancer risk: A meta‐analysis of randomized controlled trials

Folic acid supplementation and cancer risk: A meta‐analysis of randomized controlled trials

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

The association between atorvastatin administration and plasma total homocysteine levels in renal transplant recipients

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