Atorvastatin in Patients with Type 2 Diabetes Mellitus Undergoing Hemodialysis

Wanner, Christoph; Krane, Vera; März, Winfried; Olschewski, Manfred; Mann, Johannes F.E.; Ruf, G.; Ritz, Eberhard

doi:10.1056/nejmoa043545

Cited by 2,314 publications

(1,308 citation statements)

References 26 publications

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“…the primary mediators or the "missing link" that explains the burden of CVD in patients with CKD (15). Although statins reduced the incidence of cardiovascular events in patients with type 2 diabetes (16), these findings were not confirmed in patients who were on hemodialysis in a recently published large, prospective study (17).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Panichi et al (17) described that simvastatin in commonly used dosages has an in vitro and in vivo anti-inflammatory effect in patients with CKD. Our study confirms the findings of other authors (21,22), showing that patients with CKD have higher levels of inflammatory markers, such as CRP, IL-1␤, IL-6, and TNF-␣, than general population.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Atorvastatin on Inflammatory and Fibrinolytic Parameters in Patients with Chronic Kidney Disease

Goicoechea

Vinuesa

Lahera

et al. 2006

Journal of the American Society of Nephrology

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Although substantial evidence suggests that treatment of dyslipidemia with statins reduces mortality and morbidity that are associated with cardiovascular disease, only a few studies have examined the efficacy of statins on inflammatory and fibrinolytic status in patients with chronic kidney disease (CKD). A 6-mo, prospective, randomized study was designed to assess the efficacy of atorvastatin in reducing circulating inflammatory and fibrinolytic parameters in patients with CKD. Sixty-six patients with CKD (stages 2, 3, and 4) and LDL cholesterol levels >100 mg/dl were randomly assigned (2:1) to receive 20 mg/d atorvastatin (n ‫؍‬ 44) or nonatorvastatin therapy (n ‫؍‬ 22). Lipid profile, renal function, fibrinolytic balance (tissue plasminogen activator [t-PA] and plasminogen activator inhibitor-1), and inflammatory markers (C-reactive protein [CRP], IL-1␤, IL-6, and TNF-␣) were measured before and 6 mo after atorvastatin was added to the treatment. Twenty-five age-matched individuals with normal renal function (estimated GFR >90 ml/min) were used as healthy control subjects. Patients with CKD had higher CRP, IL-1␤, TNF-␣, and IL-6 levels than age-matched population with normal renal function. t-PA concentration was higher in patients with CKD (P ‫؍‬ 0.000). Plasminogen activator inhibitor-1 values were comparable in all patients. Total cholesterol and LDL cholesterol were significantly reduced only in patients who received atorvastatin. In addition to the hypolipidemic effect, atorvastatin treatment significantly reduced inflammatory parameters: CRP (median 4.1 to 2.9; P ‫؍‬ 0.015), TNF-␣ (6.0 ؎ 2.7 to 4.7 ؎ 2.4; P ‫؍‬ 0.046), and IL-1␤ levels (1.9 ؎ 0.7 to 1.2 ؎ 0.7; P ‫؍‬ 0.001). These parameters remained unchanged in patients who were not treated with atorvastatin. Fibrinolytic parameters were not modified by atorvastatin treatment. Patients with CKD showed higher levels of inflammatory parameters and t-PA levels than age-matched healthy control subjects. Atorvastatin treatment, in addition to its beneficial effect on cholesterol levels, improved the inflammatory state of these patients without modifying fibrinolytic balance. P atients with chronic kidney disease (CKD) have a markedly higher prevalence of cardiovascular disease (CVD) than the general population (1,2). They have an altered plasma lipid profile that is characterized by increased levels of triglycerides, decreased levels of HDL cholesterol, and no consistent change in LDL cholesterol (3). Furthermore, dyslipidemia is considered a major cause of CVD in patients with CKD, and management of dyslipidemia plays an important role in the therapy of these patients (4,5).It has been established that the benefits of hepatic hydroxymethyl glutaryl-CoA reductase inhibitors, or statins, in cardiovascular disease can be explained not only by their lipid-lowering potential but also by non-lipid-related mechanisms, the so-called "pleiotropic effects." Some of these beneficial effects are related to the anti-inflammatory and fibrinolytic properties of statins,...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of Atorvastatin on Inflammatory and Fibrinolytic Parameters in Patients with Chronic Kidney Disease

Goicoechea

Vinuesa

Lahera

et al. 2006

Journal of the American Society of Nephrology

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“…Atorvastatin (20 mg daily) during a median of 4 years follow-up did not significantly reduce the primary end point of combined cardiovascular events or mortality. Hence, we investigated the association of plasma a-tocopherol concentrations as a major part of vitamin E with stroke and other cardiovascular and fatal events in the large, well characterized 4D study population of 1255 diabetic hemodialysis patients (13).…”

Section: Introductionmentioning

confidence: 99%

Low Plasma α-Tocopherol Concentrations and Adverse Clinical Outcomes in Diabetic Hemodialysis Patients

Espe

Raila

Henze

et al. 2013

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of a-tocopherol and specific clinical outcomes in diabetic hemodialysis patients.Design, settings, participants, & measurements In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), a-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma a-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508).Results Patients had a mean age of 6668 years, and mean plasma a-tocopherol level was 22.869.6 mmol/L. Levels of a-tocopherol were highly correlated to triglycerides (r=0.63, P,0.001). Patients in the lowest a-tocopherol quartile had (in unadjusted analyses) a 79% higher risk of stroke and a 31% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratio stroke =1.56, 95% confidence interval=0.75-3.25; hazard ratio mortality =1.22, 95% confidence interval=0.89-1.69, respectively). There was no association between a-tocopherol and myocardial infarction, sudden death, or infectious death.Conclusions Plasma a-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients.

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“…However, cardiovascular disease in the ESRD population has unique aspects. This is exemplified best by the results of the 4-D trial, in which control of hypercholesterolemia failed to improve mortality among dialysis patients (3). Approaches to preventing cardiovascular death among dialysis patients requires an approach that is tailored to the particular aspects of cardiac disease in uremia.…”

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confidence: 99%

Left Ventricular Hypertrophy

Achinger

Ayus

2006

Journal of the American Society of Nephrology

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Cardiovascular disease occurs in ESRD patients at rates that are far higher than is seen in the general population, and cardiovascular deaths account for the majority of deaths among dialysis patients. Abnormal mineral metabolism is a novel cardiovascular risk factor among dialysis patients. Recently published results demonstrated that even with good control of BP and anemia, conventional hemodialysis is associated with significant left ventricular hypertrophy (LVH); however, daily hemodialysis was associated with a significant reduction in LV mass index (LVMI). Furthermore, it was shown that control of serum phosphorus correlates with the reduction in LVMI. These data suggest a novel mechanism for the deleterious effect of elevated serum phosphorus on cardiovascular outcomes among hemodialysis patients: LVH. Other investigators have noted an association of hyperphosphatemia and LVH; however, this study was the first to demonstrate that improvement in serum phosphorus is associated with reduction in LVM. In addition, it is shown that daily hemodialysis is an effective modality in improving serum phosphorus through significantly improved phosphorus removal. Elevated serum phosphorus leads to vascular calcification, which can lead to LVH by decreasing vascular compliance. However, our study showed an improvement in LVMI during a 12-mo period. Because vascular calcification is unlikely to remit over this time period, it is proposed that serum phosphorus has a reversible, cardiotoxic effect that leads to LVH that can be reversed successfully with good control of serum phosphorus.

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Atorvastatin in Patients with Type 2 Diabetes Mellitus Undergoing Hemodialysis

Abstract: Atorvastatin had no statistically significant effect on the composite primary end point of cardiovascular death, nonfatal myocardial infarction, and stroke in patients with diabetes receiving hemodialysis.

Cited by 2,314 publications

References 26 publications

Effects of Atorvastatin on Inflammatory and Fibrinolytic Parameters in Patients with Chronic Kidney Disease

Effects of Atorvastatin on Inflammatory and Fibrinolytic Parameters in Patients with Chronic Kidney Disease

Low Plasma α-Tocopherol Concentrations and Adverse Clinical Outcomes in Diabetic Hemodialysis Patients

Left Ventricular Hypertrophy

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