Biologics May Prevent Cardiovascular Events in Rheumatoid Arthritis by Inhibiting Coronary Plaque Formation and Stabilizing High-Risk Lesions.

ObjectiveTo evaluate whether biologic disease-modifying antirheumatic drugs (DMARDs) decrease cardiovascular disease (CVD) risk in rheumatoid arthritis (RA) and whether biologic DMARDs might have a beneficial effect on coronary plaque formation or progression.MethodsIn this single-center observational cohort study, 150 patients underwent computed tomographic angiography for evaluation of coronary atherosclerosis (total, noncalcified, mixed/calcified, and low-attenuation plaque); 101 had repeat assessments within a mean ± SD of 6.9 ± 0.3 years to evaluate plaque progression. All CVD events were prospectively recorded, including cardiac death, myocardial infarction, unstable angina, revascularization, stroke, claudication, and hospitalization for heart failure. The Framingham-D'Agostino score was used to assess cardiovascular risk. The segment stenosis score was used to measure plaque burden. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.ResultsAfter adjustment for the segment stenosis score, the Framingham-D'Agostino score, and time-varying Disease Activity Score in 28 joints using the C-reactive protein level using marginal structural models, current biologic DMARD use was associated with lower long-term CVD risk (OR 0.15 [95% CI 0.04-0.60]). Noncalcified and low-attenuation plaque presence moderated the effect of biologic DMARDs on CVD risk; specifically, biologic DMARD use was associated with lower CVD risk in patients with noncalcified or low-attenuation plaque at baseline (OR 0.21 [95% CI 0.04-0.99] and OR 0.08 [95% CI 0.01-0.70], respectively), but not in those without noncalcified or low-attenuation plaque. Per-segment plaque progression analyses showed that biologic DMARD exposure was associated with transition of noncalcified to mixed/calcified plaque (OR 4.00 [95% CI 1.05-15.32]). Biologic DMARD exposure predicted a lower likelihood of new plaque forming in segments without plaque among patients without mixed/calcified plaque in other coronary segments (OR 0.40 [95% CI 0.17-0.93]), but not among those with calcification. Biologic DMARD treatment also predicted low-attenuation plaque loss (P = 0.042).ConclusionOur findings indicate that in RA, biologic DMARD use is associated with reduced CVD risk, protective calcification of noncalcified lesions, and lower likelihood of new plaque formation in patients with early atherosclerosis

Microbial differences between dental plaque and historic dental calculus are related to oral biofilm maturation stage

Dental calculus, calcified oral plaque biofilm, contains microbial and host biomolecules that can be used to study historic microbiome communities and host responses. Dental calculus does not typically accumulate as much today as historically, and clinical oral microbiome research studies focus primarily on living dental plaque biofilm. However, plaque and calculus reflect different conditions of the oral biofilm, and the differences in microbial characteristics between the sample types have not yet been systematically explored. Here, we compare the microbial profiles of modern dental plaque, modern dental calculus, and historic dental calculus to establish expected differences between these substrates.- Background - Results -- Authentication of a preserved oral biofilm in calculus samples -- Dental calculus and plaque biofilm communities are distinct -- Health-associated communities of dental plaque and calculus are distinct -- Signatures of health and of disease are shared in modern and historic calculus samples -- Microbial community differences between health and disease in calculus are poorly resolved -- Absence of caries-specific microbial profiles in dental calculus -- Microbial co-exclusion patterns in plaque and calculus reflect biofilm maturity -- Microbial complexes in plaque and calculus -- Functional prediction in calculus is poorly predictive of health status -- Proteomic profiles of historic healthy site calculus -- Correlations between taxonomic, proteomic, and metabolomic profiles - Discussion - Conclusions - Materials and methods --Historic and modern calculus sample collection DNA extraction -- DNA library construction and high-throughput sequencing -- DNA sequence processing -- Genetic assessment of historic calculus sample preservation -- Genetic microbial taxonomic profiling -- Principal component analysis -- Assessment of differentially abundant taxa -- Sparse partial least squares-discriminant analysis -- Assessment of microbial co-exclusion patterns -- Gene functional categorization with SEED -- Proteomics -- Metabolomics -- Regularized canonical correlation analysi

Characterization of bacteriophage communities and CRISPR profiles from dental plaque.

BackgroundDental plaque is home to a diverse and complex community of bacteria, but has generally been believed to be inhabited by relatively few viruses. We sampled the saliva and dental plaque from 4 healthy human subjects to determine whether plaque was populated by viral communities, and whether there were differences in viral communities specific to subject or sample type.ResultsWe found that the plaque was inhabited by a community of bacteriophage whose membership was mostly subject-specific. There was a significant proportion of viral homologues shared between plaque and salivary viromes within each subject, suggesting that some oral viruses were present in both sites. We also characterized Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) in oral streptococci, as their profiles provide clues to the viruses that oral bacteria may be able to counteract. While there were some CRISPR spacers specific to each sample type, many more were shared across sites and were highly subject specific. Many CRISPR spacers matched viruses present in plaque, suggesting that the evolution of CRISPR loci may have been specific to plaque-derived viruses.ConclusionsOur findings of subject specificity to both plaque-derived viruses and CRISPR profiles suggest that human viral ecology may be highly personalized

Atherosclerotic carotid plaque composition: a 3T and 7T MRI-histology correlation study

Background and Purpose Carotid artery atherosclerotic plaque composition may influence plaque stability and risk of thromboembolic events, and non-invasive plaque imaging may therefore permit risk stratification for clinical management. Plaque composition was compared using non-invasive in-vivo (3T) and ex-vivo (7T) MRI and histopathological examination. Methods Thirty three endarterectomy cross sections, from 13 patients, were studied. The datasets consisted of in-vivo 3T MRI, ex-vivo 7T MRI and histopathology. Semi-automated segmentation methods were used to measure areas of different plaque components. Bland- Altman plots and mean difference with 95% confidence interval were carried out. Results There was general quantitative agreement between areas derived from semi-automated segmentation of MRI data and histology measurements. The mean differences and 95% confidence bounds in the relative to total plaque area between 3T versus Histology were: fibrous tissue 4.99 % (-4.56 to 14.56), lipid-rich/necrotic core (LR/NC) with haemorrhage - 1.81% (-14.11 to 10.48), LR/NC without haemorrhage -2.43% (-13.04 to 8.17), and calcification -3.18% (-11.55 to 5.18). The mean differences and 95% confidence bounds in the relative to total plaque area between 7T and histology were: fibrous tissue 3.17 % (-3.17 to 9.52), LR/NC with haemorrhage -0.55% (-9.06 to 7.95), LR/NC without haemorrhage - 12.62% (-19.8 to -5.45), and calcification -2.43% (-9.97 to 4.73). Conclusions This study provides evidence that semi-automated segmentation of 3T/7T MRI techniques can help to determine atherosclerotic plaque composition. In particular, the high resolution of ex-vivo 7T data was able to highlight greater detail in the atherosclerotic plaque composition. High field MRI may therefore have advantages for in vivo carotid plaque MR imaging

On the topology of the inverse limit of a branched covering over a Riemann surface

We introduce the Plaque Topology on the inverse limit of a branched covering self-map of a Riemann surface of a finite degree greater than one. We present the notions of regular and irregular points in the setting of this Plaque Inverse Limit and study its local topological properties at the irregular points. We construct certain Boolean Algebra and certain sigma-lattice, derived from it, and use them to compute local topological invariants of the Plaque Inverse Limit. Finally, we obtain several results interrelating the dynamics of the forward iterations of the self-map and the topology of the Plaque Inverse Limit.Comment: 25 page

The role of biomechanics in the assessment of carotid atherosclerosis severity: a numerical approach

Numerical fluid biomechanics has been proved to be an efficient tool for understanding vascular diseases including atherosclerosis. There are many evidences that atherosclerosis plaque formation and rupture are associated with blood flow behavior. In fact, zones of low wall shear stress are vivid areas of proliferation of atherosclerosis, and in particular, in the carotid artery. In this paper a model is presented for investigating how the presence of the plaque influences the distribution of the wall shear stress. In complement to a first approach with rigid walls, an FSI model is developed as well to simulate the coupling between the blood flow and the carotid artery deformation. The results show that the presence of the plaque causes an attenuation of the WSS in the after-plaque region as well as the emergence of recirculation areas

Assessing the association between oral hygiene and preterm birth by quantitative light-induced fluorescence

The aim of this study was to investigate the purported link between oral hygiene and preterm birth by using image analysis tools to quantify dental plaque biofilm. Volunteers (η = 91) attending an antenatal clinic were identified as those considered to be “at high risk” of preterm delivery (i.e., a previous history of idiopathic preterm delivery, case group) or those who were not considered to be at risk (control group). The women had images of their anterior teeth captured using quantitative light-induced fluorescence (QLF). These images were analysed to calculate the amount of red fluorescent plaque (ΔR%) and percentage of plaque coverage. QLF showed little difference in ΔR% between the two groups, 65.00% case versus 68.70% control, whereas there was 19.29% difference with regard to the mean plaque coverage, 25.50% case versus 20.58% control. A logistic regression model showed a significant association between plaque coverage and case/control status (Ρ = 0.031), controlling for other potential predictor variables, namely, smoking status, maternal age, and body mass index (BMI)

Quantification of atherosclerotic plaque volume in coronary arteries by computed tomographic angiography in subjects with and without diabetes.

BackgroundDiabetes mellitus (DM) is considered a cardiovascular risk factor. The aim of this study was to analyze the prevalence and volume of coronary artery plaque in patients with diabetes mellitus (DM) vs. those without DM.MethodsThis study recruited consecutive patients who underwent coronary computed tomography (CT) angiography (CCTA) between October 2016 and November 2017. Personal information including conventional cardiovascular risk factors was collected. Plaque phenotypes were automatically calculated for volume of different component. The volume of different plaque was compared between DM patients and those without DM.ResultsAmong 6381 patients, 931 (14.59%) were diagnosed with DM. The prevalence of plaque in DM subjects was higher compared with nondiabetic group significantly (48.34% vs. 33.01%, χ = 81.84, P < 0.001). DM was a significant risk factor for the prevalence of plaque in a multivariate model (odds ratio [OR] = 1.465, 95% CI: 1.258-1.706, P < 0.001). The volume of total plaque and any plaque subtypes in the DM subjects was greater than those in nondiabetic patients significantly (P < 0.001).ConclusionThe coronary artery atherosclerotic plaques were significantly higher in diabetic patients than those in non-diabetic patients

Orthopedic surgery increases atherosclerotic lesions and necrotic core area in ApoE-/- mice

Background and aims Observational studies show a peak incidence of cardiovascular events after major surgery. For example, the risk of myocardial infarction increases 25-fold early after hip replacement. The acuteness of this increased risk suggests abrupt enhancement in plaque vulnerability, which may be related to intra-plaque inflammation, thinner fibrous cap and/or necrotic core expansion. We hypothesized that acute systemic inflammation following major orthopedic surgery induces such changes. Methods ApoE−/− mice were fed a western diet for 10 weeks. Thereafter, half the mice underwent mid-shaft femur osteotomy followed by realignment with an intramedullary K-wire, to mimic major orthopedic surgery. Mice were sacrificed 5 or 15 days post-surgery (n = 22) or post-saline injection (n = 13). Serum amyloid A (SAA) was measured as a marker of systemic inflammation. Paraffin embedded slides of the aortic root were stained to measure total plaque area and to quantify fibrosis, calcification, necrotic core, and inflammatory cells. Results Surgery mice showed a pronounced elevation of serum amyloid A (SAA) and developed increased plaque and necrotic core area already at 5 days, which reached significance at 15 days (p = 0.019; p = 0.004 for plaque and necrotic core, respectively). Macrophage and lymphocyte density significantly decreased in the surgery group compared to the control group at 15 days (p = 0.037; p = 0.024, respectively). The density of neutrophils and mast cells remained unchanged. Conclusions Major orthopedic surgery in ApoE−/− mice triggers a systemic inflammatory response. Atherosclerotic plaque area is enlarged after surgery mainly due to an increase of the necrotic core. The role of intra-plaque inflammation in this response to surgical injury remains to be fully elucidated. © 2016 Elsevier Ireland Lt