Effects of atorvastatin on reactive hyperemia and inflammatory process in patients with congestive heart failure

Tousoulis, Dimitris; Antoniades, Charalambos; Kotsopoulou, Maria; Pitsavos, Christos; Vlachopoulos, Charalambos; Panagiotakos, D.; Stefanadis, Christodoulos

doi:10.1016/j.atherosclerosis.2004.08.037

Cited by 92 publications

(61 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, it has been proposed that statins have beneficial effects beyond lipid lowering. Such effects might be related to reduction in inflammatory reactions, inhibition of platelet aggregation or improvement in endothelial function [20, 21]. In the present study, we demonstrated that simvastatin inhibited CRP-induced pro-inflammatory responses in endothelial cells.…”

Section: Discussionsupporting

confidence: 66%

Simvastatin Inhibits C-Reactive Protein-Induced Pro-Inflammatory Changes in Endothelial Cells by Decreasing Mevalonate Pathway Products

et al. 2007

View full text Add to dashboard Cite

Objectives: The effects of HMG-CoA reductase inhibitors on C-reactive protein (CRP)-induced pro-inflammatory changes in endothelial cells remain unclear. We tested the hypothesis that simvastatin inhibited CRP-induced pro-inflammatory changes in endothelial cells by decreasing mevalonate pathway products. Methods: Human umbilical vein endothelial cells were incubated with CRP and measurement of CD32, nuclear factor ĸB (NF-ĸB) activation, vascular cell adhesion molecule-1 expression and monocyte adhesion assay were performed. The effects of simvastatin, siRNA against CD32 (siCD32) and mevalonate pathway products were also examined. Results: Pre-treatment with simvastatin significantly attenuated the CRP-induced CD32 expression and NF-ĸB activation in human umbilical vein endothelial cells. Simvastatin also decreased CRP-induced vascular cell adhesion molecule-1 expression and reduced monocyte adhesion on endothelial cells. The inhibitory effects of simvastatin were significantly reversed by adding mevalonate and geranylgeranyl pyrophosphate (GGPP), but not by adding farnesyl pyrophosphate. Pre-treatment with siCD32 also decreased CRP-induced CD32 expression and inhibitor of ĸB degradation. However, neither mevalonate nor GGPP reversed the effects of siCD32. Conclusions: CRP-induced CD32 expression and NF-ĸB activation were attenuated by simvastatin. A decrease in mevalonate and subsequent GGPP contributes to the inhibitory effects of simvastatin. These findings may provide an explanation of using statins on patients with high serum CRP levels.

show abstract

Section: Discussionsupporting

confidence: 66%

Simvastatin Inhibits C-Reactive Protein-Induced Pro-Inflammatory Changes in Endothelial Cells by Decreasing Mevalonate Pathway Products

et al. 2007

View full text Add to dashboard Cite

show abstract

“…34 Short-term statin therapy also has been shown to improve endothelial function in chronic HF patients, even after adjustment for cholesterol level. 35,36 Although this is the largest study to date to assess the impact of statin therapy in a nationally representative cohort of older patients hospitalized with HF, there are outstanding issues to consider. This study was an observational study and does not have the strength of a randomized clinical trial, so its conclusions should be handled with important reservations.…”

Section: Foody Et Al Statins and Mortality In Heart Failurementioning

confidence: 99%

Statins and Mortality Among Elderly Patients Hospitalized With Heart Failure

et al. 2006

View full text Add to dashboard Cite

Background— Small studies suggest that statins may improve mortality in patients with heart failure (HF). Whether these results are generalizable to a broader group of patients with HF remains unclear. Our objective was to evaluate the association between statin use and survival among a national sample of elderly patients hospitalized with HF. Methods and Results— A nationwide sample of 61 939 eligible Medicare beneficiaries ≥65 years of age who were hospitalized with a primary discharge diagnosis of HF between April 1998 and March 1999 or July 2000 and June 2001 was evaluated. The analysis was restricted to patients with no contraindications to statins (n=54 960). Of these patients, only 16.7% received statins on discharge. Older patients were less likely to receive a statin at discharge. Patients with hyperlipidemia and those cared for by a cardiologist or cared for in a teaching hospital were more likely to receive a statin at discharge. In a Cox proportional hazards model that took into account demographic, clinical characteristics, treatments, physician specialty, and hospital characteristics, discharge statin therapy was associated with significant improvements in 1- and 3-year mortality (hazard ratio, 0.80; 95% CI, 0.76 to 0.84; and hazard ratio, 0.82; 95% CI, 0.79 to 0.85, respectively). Regardless of total cholesterol level or coronary artery disease status, statin therapy was associated with significant differences in mortality. Conclusions— Our data demonstrate that statin therapy is associated with better long-term mortality in older patients with HF. This study suggests a potential role for statins as an adjunct to current HF therapy. Randomized clinical trials are required to determine the role of these agents in improving outcomes in the large and growing group of patients with HF.

show abstract

“…7 For example, statins may induce angiogenesis by recruiting bone marrow stem cells, 8 reduce levels of inflammatory factors, and improve endothelial function. 9,10 On the other hand, epidemiological studies have observed a higher risk of adverse events with low levels of low-density lipoprotein cholesterol in persons with heart failure. 11,12 Statins may diminish the ability of lipoproteins to bind endotoxins leading to stimulation of proinflammatory cytokines 13 ; reduce levels of coenzyme Q 10 14 and selenoproteins, 15 which could adversely affect cardiac muscle and function; and have deleterious interactions with medications commonly used for heart failure, such as digoxin.…”

mentioning

confidence: 99%

“…9,10 On the other hand, epidemiological studies have observed a higher risk of adverse events with low levels of low-density lipoprotein cholesterol in persons with heart failure. 11,12 Statins may diminish the ability of lipoproteins to bind endotoxins leading to stimulation of proinflammatory cytokines 13 ; reduce levels of coenzyme Q 10 14 and selenoproteins, 15 which could adversely affect cardiac muscle and function; and have deleterious interactions with medications commonly used for heart failure, such as digoxin. 16 Therefore, we examined the association of incident statin use on the risks of death and hospitalization within a large, diverse population of patients with heart failure who were considered eligible for lipid-lowering therapy.…”

mentioning

confidence: 99%