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

Abstract

BackgroundAtrial 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.FindingsAnalysis 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-γ (IFNγ) 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-1β (MIP-1β) 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.ConclusionsAnti-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 Trials.govNCT00449410

The Association Between Reduced Inflammation and Cognitive Gains After Bariatric Surgery

“…Similarly, the reliance on hs-CRP as a marker of inflammation may have contributed to our findings, as obesity is associated with elevations in many inflammatory markers(21–23), including some that may be more closely associated with cognitive function(28,43). For example, in persons with a trial fibrillation, reductions in markers such as interleukin (IL)-2, IL-9, and IL-12 predicted improved cognitive function but CRP did not(44). Additional work is much needed to clarify the possible contribution of inflammation to cognitive function in obese persons, especially given the recent findings that reduced inflammation following bariatric surgery was associated with reduced expression of Alzheimer’s disease-related genes(31).…”

Roles and Mechanisms of Interleukin-12 Family Members in Cardiovascular Diseases: Opportunities and Challenges

“…All IL-12 family members can be secreted by both immune and non-immune cells (Vignali and Kuchroo, 2012;Sun et al, 2015). For the immune cells, IL-12, IL-23, and IL-27 are mainly derived from effector T lymphocytes, macrophages, and dendritic cells, while IL-35 is mainly secreted by T helper cells (Tregs) (Langrish et al, 2004;Hunter, 2005;Collison et al, 2009;Collison et al, 2010;Andrews et al, 2016;Wei et al, 2017). IL-12 and IL-23 are considered to be pro-inflammatory factors that amplify downstream inflammatory signals.…”

Links between parameters of long-term latent memory and progression from paroxysmal to permanent atrial fibrillation during a five-year observation period. A preliminary study

“…The following pathomechanisms of the relationships between AF and cognitive impairment have been suggested: (a) stroke due to embolus of a cerebral artery; (b) asymptomatic cerebral artery microembolism with mate-rial of cardiac origin, e.g. due to insufficient anticoagulation; (c) haemodynamic complications of atrial arrhythmia leading to a decrease in cerebral blood flow; (d) anticoagulation complications with haemorrhagic stroke; (e) systolic or diastolic cardiac failure; and (f) the effect of characteristics and comorbidities leading to heart and vascular injury, such as: increased age, gender, hypertension, diabetes mellitus, hyperlipidaemia, obesity, low physical activity, and systemic inflammatory status [10,[13][14][15][16][17][18]. Relationships between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and left atrium dilatation are also reported [19][20][21].…”