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

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

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

Aged garlic extract reduces low attenuation plaque in coronary arteries of patients with diabetes: A randomized, double-blind, placebo-controlled study.

Several previous studies have demonstrated that aged garlic extract (AGE) inhibits the progression of coronary artery calcification and non-calcified plaque (NCP) in the general population. However, its effects on plaque progression in patients with diabetes have not yet been investigated, at least to the best of our knowledge. This study investigated whether AGE reduces the coronary plaque volume measured by cardiac computed tomography angiography (CCTA) in patients with diabetes mellitus (DM). A total of 80 participants with DM with a median age of 57 years were prospectively assigned to consume 2,400 mg AGE/day (after completion, 37 participants) or placebo (after completion, 29 participants) orally. Both groups underwent CCTA at baseline and follow-up 365 days apart. In total, 66 participants completed the study. Coronary plaque volume, including total plaque (TP), dense calcium (DC), fibrous, fibro-fatty and low-attenuation plaque (LAP) volumes were measured based upon pre-defined intensity cut-off values using semi-automated software (QAngio CT). Changes in various plaque types were normalized to the total coronary artery length. The non-parametric Wilcoxon rank-sum test was performed to examine the differences in plaque formation between the 2 groups. No significant differences were found in the baseline characteristics between the AGE and placebo groups. Compared with the placebo group, the AGE group exhibited a statistically significant regression in normalized LAP [median and standard deviation (SD) -0.2 (18.8) vs. 2.5 (69.3), P=0.0415]. No differences were observed in TP, fibrous, or fibrofatty plaque volumes between the AGE and placebo group. On the whole, this study indicated that the %LAP change in the AGE group was significantly greater than that in the placebo group in patients with diabetes. However, further studies are warranted to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events

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

Mathematical models for vulnerable plaques

A plaque is an accumulation and swelling in the artery walls and typically consists of cells, cell debris, lipids, calcium deposits and fibrous connective tissue. A person is likely to have many plaques inside his/her body even if they are healthy. However plaques may become "vulnerable", "high-risk" or "thrombosis-prone" if the person engages in a high-fat diet and does not exercise regularly. In this study group, we proposed two mathematical models to describe plaque growth and rupture. The first model is a mechanical one that approximately treats the plaque as an inflating elastic balloon. In this model, the pressure inside the core increases and then decreases suggesting that plaque stabilization and prevention of rupture is possible. The second model is a biochemical one that focuses on the role of MMPs in degrading the fibrous plaque cap. The cap stress, MMP concentration, plaque volume and cap thickness are coupled together in a system of phenomenological equations. The equations always predict an eventual rupture since the volume, stresses and MMP concentrations generally grow without bound. The main weakness of the model is that many of the important parameters that control the behavior of the plaque are unknown. The two simple models suggested by this group could serve as a springboard for more realistic theoretical studies. But most importantly, we hope they will motivate more experimental work to quantify some of the important mechanical and biochemical properties of vulnerable plaques

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)

Noninvasive imaging of focal atherosclerotic lesions using fluorescence molecular tomography

Insights into the etiology of stroke and myocardial infarction suggest that rupture of unstable atherosclerotic plaque is the precipitating event. Clinicians lack tools to detect lesion instability early enough to intervene, and are often left to manage patients empirically, or worse, after plaque rupture. Noninvasive imaging of the molecular events signaling prerupture plaque progression has the potential to reduce the morbidity and mortality associated with myocardial infarction and stroke by allowing early intervention. Here, we demonstrate proof-of-principle in vivo molecular imaging of C-type natriuretic peptide receptor in focal atherosclerotic lesions in the femoral arteries of New Zealand white rabbits using a custom built fiber-based, fluorescence molecular tomography (FMT) system. Longitudinal imaging showed changes in the fluorescence signal intensity as the plaque progressed in the air-desiccated vessel compared to the uninjured vessel, which was validated by ex vivo tissue studies. In summary, we demonstrate the potential of FMT for noninvasive detection of molecular events leading to unstable lesions heralding plaque rupture