Improved neurocognitive functions correlate with reduced inflammatory burden in atrial fibrillation patients treated with intensive cholesterol lowering therapy

Contains fulltext : 119310.pdf (publisher's version ) (Open Access)BACKGROUND: Atrial fibrillation (AF) is associated with increased mortality and morbidity, including risk for cerebral macro- and microinfarctions and cognitive decline, even in the presence of adequate oral anticoagulation. AF is strongly related to increased inflammatory activity whereby anti-inflammatory agents can reduce the risk of new or recurrent AF. However, it is not known whether anti-inflammatory therapy can also modify the deterioration of neurocognitive function in older patients with AF. In the present study, older patients with AF were treated with intensive lipid-lowering therapy with atorvastatin 40 mg and ezetimibe 10 mg, or placebo. We examined the relationship between neurocognitive functions and inflammatory burden. FINDINGS: Analysis of inflammatory markers revealed significant reductions in high sensitivity C-reactive protein (hs-CRP), fibroblast growth factor (FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 receptor antagonist (IL-1RA), interleukin (IL)-9, IL-13 and IL-17, and interferon-gamma (IFNgamma) in the treatment group compared to placebo. Reduction in plasma concentration of IL-1RA, IL-2, IL-9 and IL-12, and macrophage inflammatory protein-1beta (MIP-1beta) correlated significantly with improvement in the neurocognitive functions memory and speed. Loss of volume in amygdala and hippocampus, as determined by magnetic resonance imaging (MRI), was reduced in the treatment arm, statistically significant for left amygdala. CONCLUSIONS: Anti-inflammatory therapy through intensive lipid-lowering treatment with atorvastatin 40 mg and ezetimibe 10 mg can modify the deterioration of neurocognitive function, and the loss of volume in certain cerebral areas in older patients with AF. TRIAL REGISTRATION CLINICAL TRIALSGOV: NCT00449410

Persisting thrombin activity in elderly patients with atrial fibrillation on oral anticoagulation is decreased by anti-inflammatory therapy with intensive cholesterol-lowering treatment

Item does not contain fulltextBACKGROUND: It has been demonstrated that the occurrence of ischemic stroke is more prevalent in AF patients, when increased levels of inflammatory markers are present. OBJECTIVE: The aim of this study was to evaluate the effect of intensive cholesterol lowering therapy on inflammatory markers and evidence of thrombotic in elderly AF patients treated with OAC. METHODS: 34 elderly patients (69-85 yrs) were randomized to double blind treatment with atorvastatin 40 mg plus ezetimibe 10 mg (n = 17) or double placebo (n = 17) for one year. All were anticoagulated with warfarin (target INR 2.5-3.5). Every 3 months inflammatory markers and parameters for evaluation of haemostatic and fibrinolytic activity were measured. RESULTS: Anti-inflammatory effects in the treatment arm were reflected by a significant decrease from baseline in hs-CRP, FGF, G-CSF, GM-CSF, IL-1ra, IL-9, IL-13, IL-17 and interferon-gamma (P < .05). There was no significant decrease in the control group. Endogenous thrombin potential was still present and active but decreased during treatment (P = .0005) compared to the placebo group. After 12 months treatment, a significant correlation was found between changes in endogenous thrombin potential and hs-CRP, interferon-gamma and G-CSF, respectively. No hemorrhagic complications occurred. CONCLUSION: Intensive cholesterol lowering significantly reduced inflammation and was accompanied by reduced thrombin generation. Larger clinical studies should determine which inflammatory markers are most specific and sensitive for estimating the inflammatory burden in these patients and at which corresponding thrombin activity level it is beneficial and safe to add intensive cholesterol lowering therapy even if normal cholesterol levels are present