Reduced levels of TNFα in hypercholesterolemic individuals after treatment with pravastatin for 8 weeks

Solheim, Svein; Seljeflot, Ingebjørg; Arnesen, Harald; Eritsland, Jan; Eikvar, Lars

doi:10.1016/s0021-9150(00)00725-5

Cited by 65 publications

(39 citation statements)

References 28 publications

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“…29 In support of these findings, we have reported that in a group of patients undergoing CABG, baseline levels of IL-6 were not significantly different for those taking statins versus those not taking statins, although peak IL-6 levels 6 hours after bypass were significantly lower in the statin group, 30 indicating that statins may inhibit the acute inflammatory IL-6 increase. TNF-␣ levels have been reported to be lower in patients treated with pravastatin, 31 and in vitro pravastatin downregulates several inflammatory markers in human monocytes/macrophages 32 and also results in lower IL-6 mRNA levels in human umbilical vein endothelial cells. 33 The 1-year data from the WOSCOPS men suggests that the lower risk associated with the CC genotype in pravastatintreated patients is in part associated with a greater reduction of inflammatory markers, with the fall in CRP plasma levels being Ϸ1.7-fold greater in the CC group than in the GGϩGC group, although the difference was not statistically significant.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 −174G>C Polymorphism and Risk of Coronary Heart Disease in West of Scotland Coronary Prevention Study (WOSCOPS)

Basso

Lowe

Rumley

et al. 2002

ATVB

153

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Abstract-Interleukin (IL)-6 plays an important role in the pathogenesis of coronary heart disease (CHD). Two functional polymorphisms in the IL-6 promoter have been identified (Ϫ174GϾC and Ϫ572GϾC), with both the rare alleles being associated with higher plasma levels of IL-6 after bypass surgery and one of them (Ϫ174GϾC) associated with CHD risk.We have studied the contribution of these polymorphisms to CHD risk in the West of Scotland Coronary Prevention Study (WOSCOPS), a primary prevention trial that demonstrated the effectiveness of pravastatin in reducing morbidity and mortality from CHD. Four hundred ninety-eight cases (consisting of individuals experiencing a cardiovascular event during 4.8 years of follow-up) and 1109 controls (individuals matched for age and smoking habits) were genotyped. In the placebo group, there was no significant evidence of higher risk associated with the Ϫ174CC genotype compared with the GGϩGC group. However, in the pravastatin-treated group, CC homozygotes had a significantly lower risk of CHD compared with the GGϩGC placebo group (odds ratio 0.46, 95% CI 0.27 to 0.79), and this remained statistically significant after adjustment for classic risk factors. Compared with the GGϩGC group, men with the CC genotype had modestly, but not significantly, higher baseline levels of IL-6, C-reactive protein, or fibrinogen but showed a significantly greater fall in LDL cholesterol with statin treatment (Pϭ0.036). The Ϫ572GϾC polymorphism was not significantly associated with any plasma trait or CHD risk. Thus, in subjects under pravastatin treatment, the Ϫ174CC genotype was associated with a lower risk of CHD. These results demonstrate the importance of the inflammatory system in determining the risk of CHD and support the nonlipid effect of statins on risk.

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Section: Discussionmentioning

confidence: 99%

Interleukin-6 −174G>C Polymorphism and Risk of Coronary Heart Disease in West of Scotland Coronary Prevention Study (WOSCOPS)

Basso

Lowe

Rumley

et al. 2002

ATVB

153

View full text Add to dashboard Cite

show abstract

“…Reduction of TNF-α has been demonstrated with pharmacologic agents that modulate either the renin angiotensin system or inhibit 3-hydroxy-3-methylglutaryl conezyme A (HMG CoA) reductase. Solheim et al [13] assessed the effect of pravastatin on the levels of TNF-α and selected soluble cellular adhesion molecules. The expression of cellular adhesion molecules on the endothelium modulates inflammatory cell migration and has been demonstrated to play a role in the earliest stages of atherosclerosis.…”

Section: Tumor Necrosis Factormentioning

confidence: 99%

Atherosclerosis and inflammation

Farmer

Torre‐Amione

2002

Curr Atheroscler Rep

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The pathophysiology of coronary atherosclerosis is complex and multifactorial. The probability of the development of symptomatic coronary heart disease may be predicted by standard risk factor stratification involving hypertension, dyslipidemia, age, positive family history, and diabetes. However, risk factor stratification has been demonstrated to have significant limitations in the individual patient, which has generated a search for more specific and sensitive markers. Evidence is increasing that atherosclerosis is a disease characterized by inflammation, beginning with the earliest identifiable lesion (fatty streak) to the advanced vulnerable plaque. Clinical markers of inflammation, including C-reactive protein, modified low-density lipoprotein, homocysteine, tumor necrosis factor, and thermogenicity, have been identified as emerging risk factors that may add prognostic information in patient management. This review centers on inflammation as a potential pathogenetic factor in atherosclerosis and the role that clinical markers may play in the identification of patients at risk.

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“…Preliminary evidence suggests that administration of anti-TNF-α antibody reduces other inflammatory cytokines such as IL-6, and thus production of acute phase proteins [28]. Statin therapy has also shown to be associated with a reduction in levels of TNF-α [29]. Anti-TNF-α therapy may hold potential for prevention of coronary artery disease, as well as inhibition of restenosis following percutaneous coronary interventions.…”

Section: Anti-tumor Necrosis Factor-α Antibodymentioning

confidence: 99%

Vascular inflammation as a therapeutic target for prevention of cardiovascular disease

Clark

2002

Curr Atheroscler Rep

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Reduced levels of TNFα in hypercholesterolemic individuals after treatment with pravastatin for 8 weeks

Cited by 65 publications

References 28 publications

Interleukin-6 −174G>C Polymorphism and Risk of Coronary Heart Disease in West of Scotland Coronary Prevention Study (WOSCOPS)

Interleukin-6 −174G>C Polymorphism and Risk of Coronary Heart Disease in West of Scotland Coronary Prevention Study (WOSCOPS)

Atherosclerosis and inflammation

Vascular inflammation as a therapeutic target for prevention of cardiovascular disease

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