Coronary artery calcium and cardiovascular disease prediction by scanner type: the multi-ethnic study of atherosclerosis.

AIM: To evaluate the predictive value of coronary artery calcium (CAC) scoring methods across cardiac computed tomography (CT) scanner types. MATERIALS AND METHODS: CAC was measured in participants from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of participants free of baseline cardiovascular disease (CVD), using either EBCT (electron beam CT) or MDCT (multidetector CT). The risks for incident coronary heart disease (CHD) and CVD events were compared for CAC scores per SD using Cox proportional hazards models with multivariable adjustment in 3,362 MESA participants with detectable CAC. RESULTS: Using the Agatston score, the hazard ratio (HR) and 95% confidence interval (CI) for CHD was 1.50 (1.27,1.78) for EBCT and 1.60 (1.37,1.87) for MDCT. Using volume and density scores, the HR for CHD was 2.14 (1.71,2.68) for volume and 0.61 (0.48,0.76) for density on EBCT and 1.73 (1.42,2.11) for volume and 0.88 (0.71,1.10) for density on MDCT. Similar results were seen for CVD risk and in analyses stratified by sex, body mass index (BMI), and age. The volume and density score model demonstrated higher areas under the curve (AUC) for CHD than the Agatston score with EBCT (0.702, 95% CI: 0.666,0.738 versus 0.677, 95% CI: 0.638,0.715, p<0.001) and MDCT (0.669, 95% CI: 0.632,0.705 versus 0.660, 95% CI: 0.622,0.697, p=0.216). CONCLUSION: The CAC volume and density scores provide better risk prediction than the Agatston score for CHD and CVD events, regardless of CT scanner type. CAC density was strongly and inversely associated with CHD risk. Both density and volume score prediction were stronger for EBCT than MDCT.

Histone deacetylase inhibitors valproic acid and sodium butyrate enhance prostaglandins release in lipopolysaccharide-activated primary microglia.

Modifications of histone deacetylases (HDACs) may be involved in microglia-driven neuroinflammatory responses. Recent studies suggest that several inflammatory molecules can regulate the extent of neurodegeneration and regeneration in the central nervous system (CNS). In the present study, we investigated the effects of HDAC inhibitors (HDACi) valproic acid (VPA) and sodium butyrate (NaBut) on the release of prostaglandins (PGs) in lipopolysaccharide (LPS)-activated microglia. We found that VPA and NaBut significantly enhanced LPS-induced release of PGE2, PGD2 and 8-iso-PGF2α. In addition, both compounds increased cyclooxygenase-2 and microsomal prostaglandin E synthase immunoreactivity and gene expression in LPS-stimulated microglia. Interestingly, treatment of activated microglia with HDACi also enhanced the gene expression and the release of different pro-inflammatory cytokines. Microglia activation with LPS leads to IκB-α degradation, as well as p38, ERK1/2 and JNK MAPKs phosphorylation and thus activation, which is not affected by treatment with VPA and NaBut. Furthermore, VPA and NaBut treatment induced histone acetylation at H3-K18 in microglia. We suggest that VPA and NaBut-driven increase in PGs release in LPS-activated microglia might be regulated at the transcriptional level and involves histone hyperacetylation. Our data demonstrate that VPA and NaBut are able to modulate microglia responses to inflammatory insults and thus possibly can regulate the CNS degenerative and regenerative processes.