Impact of high-fat diet on antioxidant status, vascular wall thickening and cardiac function in adult female LDLR^–/–mice

Background: Western diet, rich in saturated fatty acids and cholesterol, is associated with increased cardiovascular risk. We thus investigated in female mice the influence of this diet on plasma antioxidant status, vascular wall thickening and cardiac function. Methods and Results: Adult female C57BL/6J wild type (WT) and LDLR–/– mice were fed a normal diet (ND) or a high-fat diet (HFD) for 17 weeks. HFD induced an increase in plasma lipids and vitamin C (Vit C) levels in both groups but at a much higher level in LDLR–/– and a decrease in plasma ascorbyl free radical levels to Vit C ratio (an endogenous oxidative stress index) in LDLR–/–. We only found a slight decrease in circulating antioxidant status evaluated by the Oxygen Radical Absorbance Capacity (ORAC) assay in WT, but not in LDLR–/–. Echocardiography evidenced an increase in arterial wall thickness in aortic arch at atherosclerosis predilection sites in HFD LDLR–/– as compared to ND LDLR–/– and HFD WT. This result was confirmed by histology. Further-more, histological examination of aortic valves showed an increase in atherosclerotic lesions. Our study, using echocardiography, show that chronic HFD does not induce any major modifications of systolic function in the both mice groups. Conclusions: High-fat intake in mice causes serious disturbances in lipid plasma levels associated to variations of circulating antioxidant status due, at least in part, to an increase in Vit C. At this stage, atherosclerotic lesions, observed in aortic arch and valve, do not impair cardiac function in HFD-fed mice.

Distribution of atrial cardiomyopathy markers and association with atrial fibrillation detected after ischaemic stroke in the SAFAS study

Background Atrial cardiomyopathy(AC)is an emerging concept explaining the pathophysiology of cardioembolic strokes in absence of atrial fibrillation(AF).A definition based on the presence of electrical abnormality(P-wave terminal force in lead V1(PTFV1)>5000µV×ms),N-Terminal pro-B-type natriuretic peptide(NT pro BNP)>250pg/mL and/or indexed left atrial diameter(LADI)>3cm/m^(2)is currently tested in the ARCADIA(AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke)trial.We set out to estimate the prevalence of AC as defined in the ARCADIA trial,its determinants and its association with AF detected after stroke(AFDAS).Methods Stepwise screening for silent Atrial Fibrillation After Stroke(SAFAS)study prospectively included 240 ischaemic stroke patients.AC markers were complete for 192 of them and 9 were not included in this analysis because AF had been diagnosed on admission.Results A total of 183 patients were analysed,of whom 57%(104 patients)met the AC criteria(79 NT-proBNP,47 PTFV1,4 LADI).In the multivariate logistic regression,C reactive protein>3mg/L(OR(95%CI)2.60(1.30 to 5.21),p=0.007)and age(OR(95%CI)1.07(1.04 to 1.10),p<0.001)were found to be independently associated with AC.After 6 months of follow-up,AFDAS was detected in 33%of AC patients and in 14%of the remaining ones(p=0.003).However,AC was not independently associated with AFDAS,contrary to left atrial volume index(>34mL/m^(2),OR 2.35(CI 1.09 to 5.06)p=0029).Conclusion AC as defined in ARCADIA is mostly based on NT pro BNP elevation(76%of patients)and is associated with age and inflammation.Moreover,AC was not independently associated with AFDAS at follow-up.The ARCADIA trial,which compares aspirin to apixaban in patients with embolic strokes of undetermined source with AC markers and must,therefore be analysed in the light of these limitations.