Presence Of Plaques Research Articles

Hypertension and Cardiovascular Outcomes in Inflammatory and Autoimmune Diseases: A Systematic Review and Meta-analysis.

This review aimed to investigate the prevalence of hypertension and cardiovascular (CV) complications in various inflammatory and autoimmune diseases (IAD). Despite recent improvements in the management of IAD, patients with IAD still have an increased CV mortality and CV complications, mostly related to CV risk factors such as hypertension and inflammation. We systematically searched MEDLINE and EMBASE libraries for controlled studies involving hypertension and CV complications in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriasis including psoriatic arthritis (PsA), Sjogren's syndrome (SS), or antineutrophil cytoplasmic antibody-associated vasculitis (AAV) between January 2000 and March 2022. We extracted data on the prevalence of hypertension and CV complications. Then, random-effects meta-analyses and exploratory multivariate meta-regression were performed to explore factors related to the prevalence of hypertension.Of 2726 studies screened, 122 were selected for the meta-analysis. The prevalence of hypertension was higher among patients with IAD than controls, with an overall unadjusted odds ratio (OR) [95% confidence interval] of 1.67 [1.58-1.76] and an adjusted OR of 1.36 [1.24-1.50]. All diseases were found to be associated with increased risk of hypertension: SLE, adjusted OR 3.40 [1.93-6.00]; psoriasis, OR 1.32 [1.16-1.51]; PsA, OR 1.49 [1.15-1.94]; RA, OR 1.28 [1.04-1.58]; SS, OR 2.02 [1.19-3.44]. Age and female sex were significantly associated with hypertension in patients with IAD. The risk of CV complications was increased: ischemic heart disease, adjusted OR 1.38 [1.21-1.57]; cerebrovascular disease, OR 1.37 [1.03-1.81]; heart failure, OR 1.28 [1.05-1.55]; atherosclerotic plaques presence, OR 2.46 [1.84-3.29].The prevalence of hypertension and CV complications is higher among patients with IAD. Screening and management of hypertension appears to be of paramount importance in these patients.

Location-specific prognostic significance of plaque burden, stenosis, and plaque morphology in coronary artery disease

Abstract Background The prognostic significance of coronary plaque localization, percentage atheroma volume (PAV), stenosis, and plaque morphology has been underexplored. Purpose To investigate the prognostic significance of plaque localization beyond plaque burden, presence of stenosis and plaque morphology. Methods Patients with no cardiac history who underwent coronary CTA were included. PAV, maximum diameter stenosis, and plaque morphology were assessed and classified into proximal, mid, or distal segments of the coronary tree. Major adverse cardiac events (MACE) were defined as death or non-fatal myocardial infarction. Results Among 2819 patients 267 events (9.5%) occurred during a median follow-up of 6.9 years. PAV of the proximal segments was strongly correlated to PAV localized at of the mid (R= 0.76) and distal segments (R = 0.74, p < 0.01 for both). When adjusted for traditional risk factors and presence of plaque on other locations, only proximal PAV was independently associated with MACE (3rd quartile HR 2.08, 95% 1.17–3.71, p=0.01 and 4th quartile HR 2.29, 95% CI 1.21–4.34, p=0.01). Similar results were seen for presence of stenosis. Proximal, mid, and distal PAV as a solitary metric (unadjusted) had similar predictive value for MACE with an AUC of 0.73 (95% CI 0.69-0.76) for proximal PAV and 0.72 (95% CI 0.68-0.76) for both mid and distal localized plaque). Similar results were obtained using diameter stenosis instead of PAV. The presence of low-attenuation plaque (LAP) in the proximal segments had additional prognostic value. Calcified or noncalcified PAV did not provide additional value beyond total location-specific PAV and presence of low-attenuation plaque. Conclusions Proximal located PAV is an independent predictor of death and non-fatal MI, while there was no incremental prognostic value of plaque localized at the mid or distal coronary segments. The presence of LAP in the proximal segments provided additional prognostic value for prediction of MACE.

Using deep learning to detect atherosclerotic plaques on carotid ultrasound images in the UK Biobank

Abstract Background Atherosclerosis is the main underlying cause of cardiovascular disease (CVD). Existing CVD risk assessment tools do not consider the burden of subclinical atherosclerosis. The presence of carotid plaques on carotid ultrasound is a well-known marker of subclinical atherosclerosis. The accumulation of population-scale data on the presence of atherosclerotic plaques, along with deep phenotyping, can allow not only to address the effectiveness of carotid ultrasound in routine clinical practice, but to shed light on the biology of atherosclerosis development. Purpose To develop an effective deep learning model for plaque detection in carotid ultrasound images in the UK Biobank. Methods We used 680 carotid ultrasound images with manually annotated plaques to train a deep learning model employing the YOLOv8 architecture. Different augmentation techniques were used to increase the generalizability of the model. The developed model was applied to automatically detect plaques in raw ultrasound images from 19,507 UK Biobank participants. Logistic and Cox regression were used to explore the associations of plaque presence and number as predicted by the model with conventional CVD risk factors and the risk of future CVD events over follow-up. To explore the genetic architecture of subclinical atherosclerosis, we conducted a genome-wide association study (GWAS) on plaque presence, followed by meta-analysis with data from the CHARGE Consortium. Results Our plaque detection model achieved high classification metrics of accuracy, sensitivity, and specificity (89.3%, 89.5%, and 89.2%, respectively) and detected atherosclerotic plaques in 44% of UK Biobank participants. As expected, plaques were more common among men than women and their prevalence increased linearly with age. Both plaque presence and number of plaques were correlated with conventional CVD risk factors including diabetes, hypertension, and hyperlipidemia, and showed strong associations with future risk of incident CVD events (Hazard Ratio for plaque presence: 1.48 [95%CI: 1.21-1.82], for 2 plaques or more: 1.65, [95% CI: 1.28-2.13]). Incorporating plaque-derived phenotypes minimally altered the C-index of the time-to-event model. GWAS meta-analysis of carotid plaque presence revealed 5 previously known loci, as well as a significant locus including the LPA gene that had not previously been associated with carotid plaque. Conclusion We have developed and implemented an efficient plaque detection model to data from the UK Biobank, which holds significant promise for studying atherosclerosis at a population-wide scale through integration with multiomics data and electronic health records.

Low density lipoprotein cholesterol and cardiovascular disease risk in patients with absence of coronary artery calcification: a multicenter cohort study

Abstract Background Low-density lipoprotein cholesterol (LDL-C) plays a central role in the development of coronary heart disease (CHD). Absence of coronary artery calcification (CAC 0), as assessed by coronary computed tomography angiography (CCTA), is associated with a favorable outcome as it indicates a low burden of atherosclerosis. However, questions remain regarding the risk of non-calcified plaque and CHD in younger patients with CAC zero, as atherosclerosis tends to be non-calcified in earlier stages. Purpose To assess if LDL-C is associated with presence of non-calcified plaque and future cardiovascular events in patients with CAC zero across the age spectrum. Methods This observational multicenter cohort study included patients aged 18 years or more who underwent CCTA between January 2008 and May 2021 with CAC zero. LDL-C was measured prior to CCTA. Patients were followed from date of CCTA to occurrence of cardiovascular event, death, or 1st of October 2022. No patients were lost to follow-up. We assessed the association between LDL-C and presence of non-calcified plaque on CCTA as adjusted odds ratios, and risk for myocardial infarction and CHD (myocardial infarction or coronary revascularization) as adjusted hazard ratios using Cox regression analyses, across different age groups. Results A total of 23,776 patients with CAC zero were included in the study. Median age was 54 years (IQR 47-61) and 14,605 (61%) were women. During median follow-up of 5.5 years, 165 (0.7%) and 427 (1.8%) experienced myocardial infarction and CHD, respectively. Overall, the prevalence of non-calcified plaque was 11.1% (n=2,650). Higher LDL-C was associated with presence of non-calcified plaque with an odds ratio of 1.21 (95% CI 1.16-1.27) per 1 mmol/L higher LDL-C. Individuals aged ≤45 years had a higher odds ratio for non-calcified plaque per 1 mmol/L higher LDL-C compared to individuals aged 46-60 and >60 years; 1.36 (95% CI 1.22-1.52), 1.22 (95% CI 1.15-1.30) and 1.13 (95% CI 1.04-1.22), respectively, p value for interaction between the youngest and oldest age group was <0.05. Overall, LDL-C was associated with higher risk for myocardial infarction and CHD with hazard ratios of 1.29 (95% CI 1.10-1.52) and 1.26 (95% CI 1.14-1.39) per 1 mmol/L higher LDL-C, despite CAC zero. Conclusions Particularly in younger patients with absence of CAC, elevated LDL-C is associated with presence of non-calcified plaque and increased risk for future cardiovascular events. These data are important for clinical practice, as they demonstrate the importance of managing LDL-C in younger individuals over the long-time horizon despite CAC zero.

Reduced inflammation assessed by pericoronary adipose tissue is associated with coronary plaque calcification

Abstract Introduction Pericoronary adipose tissue attenuation (PCAT) quantified from coronary computed tomography angiography (CCTA) is increasingly recognized as an inflammation marker in coronary artery disease (CAD). Inflamed PCAT has been linked to non-calcified plaque (NCP) and cardiovascular morbidity and mortality. Nevertheless, gaps remain in understanding how PCAT behaves during plaque stabilization. Purpose We investigated associations between coronary artery inflammation assessed by PCAT and the presence and type of coronary plaques, plaque burden, and coronary calcification. Methods An observational study involving 506 patients with suspected chronic coronary syndrome who underwent CCTA. PCAT was averaged across the proximal 40 mm segments of all three coronary vessels to represent the patient level. Plaque presence and types (calcified, mixed, and soft) were assessed. Total, NCP, and calcified plaque (CP) burdens were measured as normalized atheroma volumes. Coronary calcification was quantified using Agatson coronary artery calcification (CAC) score and categorized based on cut-offs of 0, 100, 400. Results The mean PCAT was -81.1 ±6.3 Hounsfield Unit (HU) without plaque and -79.7 ±6.0 HU with plaque (p= 0.01). PCAT differed between calcified (-81.8 HU), mixed (-79.8 HU), and soft (-77.0 HU) plaques (p<0.0001). Multivariate linear analysis (adjusted for clinical risk factors, cardiovascular medication, and tube voltage) showed PCAT positively associated with total plaque burden (estimate= 1.1 [95% CI: 0.3-1.8], p=0.004) and NCP burden (estimate= 2.4 [95% CI: 1.4-3.4]; p<0.0001), while the association with CP burden was negative, but not statistically significant (estimate= -1.7 [95%CI : -4.1-0.7], p=0.2). Multivariate linear analysis, which accounted for both calcified and non-calcified plaque, reaffirmed the positive association to NCP burden (estimate= 2.7 [95% CI: 1.7-3.7]; p<0.0001) and a significant negative association between CP burden (estimate= - 3.3 [95% CI: -5.8- -1.0]; p=0.007) and PCAT. No significant differences in PCAT levels were found among patients with a CAC score of 0 and those with CAC scores exceeding 400, or across different stages of CAC score categories (p>0.8). Conclusion PCAT increased with plaque presence, rising from calcified to mixed to soft plaques. Increased NCP burden associated with higher PCAT, while higher CP burden seemed to reduce PCAT, though not statistical significant. Interestingly, when NCP was absent, higher levels of CP burden were associated with reduced inflammation. This supports the hypothesis of plaque stabilization, proposing that calcification might stabilize the vessel and indirectly contribute to reducing inflammation.Figure 1 PCAT by plaque typesTable 1 PCAT & plaque burden

Protein signatures associated with methylation patterns of heart failure phenotypes

Abstract Introduction The heart failure (HF) syndrome is highly susceptible to the exposome. The interplay between DNA methylation (DNAm), surrogate for exposomal influences, and the plasma proteome in the progression and development of phenotypes of heart failure is unclear. We investigated the relation between methylation patterns of HF phenotypes and proteins signatures. Methods Individuals with symptomatic HF (stage C/D with HFpEF, HFmrEF and HFrEF) of the MyoVasc cohort (N=3,289) were investigated. EDTA-Plasma and DNA were extracted from peripheral blood and stored in -80°C. DNAm was measured using the Infinium MethylationEPIC v2.0 methylation array. Concentrations for 538 proteins were measured using an immuno-qPCR assay in EDTA plasma. Multivariable regression models adjusted for age and sex were used to assess the relationship between DNAm signatures and individual proteins in each phenotype. Ridge-regularized linear regression was used to generate a phenotype-specific protein-signature in relation to each methylation signature, linear regression to estimate links between protein signatures and cardiovascular traits and Cox regression relate protein signatures to clinical outcome. Results Data from 1,317 individuals with symptomatic HF were analyzed. After FDR adjustment, 310 proteins were significantly related to HFpEF methylation signature, 314 to HFmrEF and 266 to HFrEF. Of associated proteins, 49.9% (198) were found in all phenotypes, 8.82% (35) only in HFpEF, 12.1% (48) in HFmrEF and 4.79% (19) in HFrEF. Tumor necrosis, arterial hypertension and T-cell regulation pathways were enriched in all three phenotypes. NT-proBNP had the strongest association with HFrEF (β=0.95 [0.82-1.08], p<0.0001) followed by presence of plaques in carotid artery and C-reactive protein, while left ventricular mass (LVM) had stronger association with HFpEF (β=0.22 [0.11-0.33], p=0.0001). All three signatures were associated with worsening of HF (HFpEF: HR=1.93 [1.61-2.30], p<0.0001; HFmrEF: HR=1.63 [1.29-2.04], p<0.0001; HFrEF: HR=1.64 [1.38-1.95], p<0.0001) and all-cause death in HF (HFpEF: HR=1.93 [1.65-2.26], p<0.0001; HFmrEF: HR=1.95 [1.58-2.42], p<0.0001; HFrEF: HR=2.24 [1.86-2.69], p<0.0001). Methylation-associated protein signatures had stronger associations with clinical outcome than the methylation signatures themselves (p < 0.01). Conclusion This study revealed protein signatures associated with methylation patterns of HF phenotypes that shared common and unique features for HF phenotypes. Important common pathways were enriched in tumour necrosis, arterial hypertension and regulation of T cells. However, important differences between phenotypes were also revealed, e.g. NT-proBNP was strongly associated with the HFrEF protein signature and LVM with the HFpEF signature. The methylation-associated protein signatures emphasise the possible exposomal influence on HF syndrome.

Coronary artery plaque characteristics in smokers assessed by intracoronary multi-modality imaging: a NIRS-IVUS guided PROSPECT II substudy

Abstract Background Smoking is a risk factor for coronary artery disease and myocardial infarction. Purpose Among patients with myocardial infarction, we hypothesized smokers would have increased prevalence of nonculprit high-risk plaque characteristics as assessed by intracoronary multimodality imaged when compared to nonsmokers. Method This is a prespecified post-hoc analysis of the PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree). Altogether 898 patients with acute myocardial infarction with or without ST-segment elevation who after successful percutaneous coronary intervention had near-infrared spectroscopy and intravascular ultrasound imaging performed. Data on lesion location, plaque burden, and lipid content were collected. Current, former, and nonsmokers were examined regarding the presence of high-risk plaques in both culprit and nonculprit lesions as well as plaque location. High-risk plaque characteristics were defined as a maximum plaque burden (maxPB) of ≥70% and a maximum 4 mm lipid core burden index (maxLCBI4mm) of ≥324.7. Results Out of 886 patients with known smoking history, 32% were smokers, 32% former, and 37% nonsmokers. Smokers were younger (median age: smokers 59.0; former 65.5; nonsmokers 64.0 years, p<0.001) with fewer co-morbidities and presented more often with STEMI (% presenting with STEMI: smokers 22.2%; former 18.9%; nonsmokers 19.4%, p=0.006). LDL was similar but CRP was higher in smokers (median µg/mL: smokers 4.0; former 3.1; nonsmokers 2.9, p=0.004). In multivariate models of nonculprit lesion morphology smoking history was not associated with maxPB or maxLCBI4mm but was associated with presence of calcified nodules (OR: 2.88 (95% CI 1.46–5.69) p=0.002 [smokers vs nonsmokers]). Calcified nodules were also associated with number of years smoked (OR: 1.02 (95% CI 1.01–1.03) p=0.004). Smoking was not associated with presence of ≥1 lesions with MaxLCBI4mm, ≥ 324.7, maxPB >=70% or the combination of both. Smoking was not associated with presence of plaque rupture or thrombus. Right coronary artery culprit lesions were more common in smokers and former smokers (smokers 29.9%; former 30.9%; nonsmokers 21.6%; OR: 1.12 (95% CI 1.04–1.21) p<0.001 [smokers vs nonsmokers]). Conclusion In this prospective intracoronary multimodality imaging study of patients with recent acute myocardial infarction, smoking was not associated with a higher rate of high-risk nonculprit plaques based on lipid content by NIRS or PB by IVUS when compared to former or nonsmokers. However, smoking was associated with higher presence of IVUS-detected calcified nodules, higher CRP-levels, and the right coronary artery as it angiographically was a more common site for culprit lesions. These results indicate that the elevated risk in smokers is unrelated to vulnerable plaque morphology defined by high PB and lipid content, and instead possibly related to inflammation, calcification, or hemodynamic changes.Table 1

Relationship of cumulative low-density lipoprotein cholesterol with atherosclerosis

Abstract Background The relationship between cumulative low-density lipoprotein cholesterol (LDL-C) exposure and progression of atherosclerosis remains uncertain. Objective The aim of this study was to determine the relationship between cumulative LDL-C level and flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation (NID) and the presence of plaque in the common carotid artery (CCA). Methods This was a cross-sectional study. We measured FMD in 8208 subjects, NID in 1822 subjects, and CCA plaque in 591 subjects who were not taking lipid-lowering drugs. The subjects were divided into four groups based on cumulative LDL-C exposure: <4000 mg･year/dL, 4000-4999 mg･year/dL, 5000-5999 mg･year/dL, and ≥6000 mg･year/dL. Results The odds ratio of the lower quartile of FMD in the cholesterol-year-score <4000 mg･year/dL group was significantly higher than the odds ratios in the other groups (Figure 1A). The odds ratio of the lower quartile of NID in the <4000 mg・year/dL group was significantly higher than the odds ratios in the 5000-5999 mg･year/dL and ≥6000 mg･year/dL groups (Figure 1B). The odds ratio of the prevalence of CCA plaque in the <4000 mg・year/dL group was significantly higher than that in the ≥6000 mg･year/dL group (Figure 1C). Conclusions Endothelial dysfunction occurred from cumulative LDL-C exposure of 4000 mg・year/dL, vascular smooth muscle dysfunction occurred from cumulative LDL-C exposure of 5000 mg･year/dL, and prevalence of CCA plaque occurred from cumulative LDL-C exposure of 6000 mg･year/dL.Graphical abstractFigure 1

Prevalence of high-risk plaque features on cardiac computed tomography scans in patients with a coronary artery calcium score of zero

Abstract Introduction Coronary artery calcium (CAC) score of zero (so-called "power of zero") is associated with a very low rate of major adverse cardiac events (MACE), especially during short and midterm follow-up. However, a CAC score of zero does not definitively exclude the presence of atherosclerotic plaques or obstructive coronary artery disease (CAD). The composition of atherosclerotic plaques and the frequency of high-risk plaque features in this population are not well described. Purpose We sought to characterize the composition of atherosclerotic plaques and assess the frequency of high-risk plaque features on contrast-enhanced computed tomography (CT) images in patients with a zero CAC score. Methods The study enrolled patients with stable chest pain suspected of CAD referred for coronary CT imaging and having a CAC score of zero. Coronary CT angiography images were assessed by an expert reader to identify atherosclerotic plaques and high-risk plaque features in all coronary arteries with a diameter ≥1.5mm. The coronary artery lumen and plaques were manually segmented, and the degree of stenosis was evaluated following the Coronary Artery Disease Reporting and Data System (CAD-RADS) criteria. The presence of four high-risk plaque features was identified: positive remodeling, spotty calcification, low-attenuation plaque, and napkin ring sign. Total plaque volume, percent atheroma volume, and plaque composition were quantified using dedicated software (Figure 1). Results A total of 145 patients (mean age 54.2±12.1 years, 35.9% males) were included in the analysis. At least one coronary artery plaque was identified in 30 individuals (20.7%). 22 (15.2%), 7 (4.8%), and 1 (0.7%) patients were categorized into CAD-RADS 1, CAD-RADS 2, and CAD-RADS 3 categories, respectively. Among 30 patients with any coronary artery plaque, at least one high-risk feature was found in 10 individuals (33.3%), while 3 individuals (10.0%) had two features. Positive remodeling was found in 7 (23.3%), spotty calcification in 3 (10.0%), low-attenuation plaque in 3 (10.0%), and napkin ring sign in 0 patients, respectively (Figure 1). The mean total plaque volume was 48.2±54.3mm³, and the mean percent atheroma volume was 1.2±0.8%. Total plaque volume comprised low-attenuation (0.4%), fibro-fatty (58.9%), fibrous (39.4%), and calcified (1.3%) plaque volumes. Notably, in 3 (10.0%) individuals, the presence of calcified plaque was identified, which on non-contrast CT images did not meet the Agatston criteria for the CAC score. Conclusions Our study demonstrates a significant prevalence of atherosclerotic plaques and high-risk plaque features in patients with a CAC score of zero. Specifically, one in every five study participants had identifiable atherosclerotic plaque, with one in every three of those exhibiting one or more high-risk plaque features. The prognostic significance of these findings warrants further evaluation in studies with longitudinal follow-up.

Screening for subclinical atherosclerosis in patients clinically diagnosed with familial hypercholesterolemia and determination of imaging-guided patient management strategy

Abstract Introduction Familial hypercholesterolemia (FH) is a monogenic dyslipidemia characterized by elevated plasma LDL-C levels, leading to early cardiovascular disease. The Dutch Lipid Clinic Network (DLCN) score is the most widely used clinical scoring system in current practice. Subclinical atherosclerosis is defined as the detection of atheromatous plaques in arterial territories, such as coronary, carotid or iliofemoral, before a symptom or event occurs. It is an early indicator of atherosclerotic burden. In this study, we investigated the presence of subclinical atherosclerosis in FH patients with a definite or probable clinical diagnosis according to DLCN score. We also tried to identify independent predictors of subclinical atherosclerosis. Methods This study is a single-center, prospective, and cross-sectional investigation involving a cohort of 215 FH patients. These patients are primary prevention patients and among them, 120 patients received a definite clinical diagnosis, while 95 patients received a probable clinical diagnosis based on the DLCN score. Carotid USG and Femoral USG were performed to screen for subclinical atherosclerosis and CAC score was calculated by non-contrast CT. Apo A-I, Apo B and Lp (a) measurements were analyzed by immunonephelometric method. Results The study population consisted of 136 (63%) women and 79 (37%) men. The mean age was 54 years (43-62) and the stigmata rate was 18%. Initially, 17% of patients were on aspirin, and 32% were receiving statin treatment; however, following subclinical atherosclerosis screening, these proportions significantly increased (aspirin usage to %32 and statin usage to %96) within the population. 148 patients (69%) had subclinical atherosclerosis in at least one site. Upon regional analysis, subclinical atherosclerosis rates were 48% in the coronary arteries, 47.5% in the carotid bifurcation region, and 40.5% in the femoral bifurcation region. Additionally, 25% of patients had atherosclerosis at one site, 27% at two sites, and 17% at all three sites. Age, male gender, pretreatment LDL-C level, Apo A-I/Apo B ratio and DM were identified as independent predictors of the presence of subclinical atherosclerosis in the FH patients. Furthermore age, male gender, pretreatment nonHDL-C level, Lp (a) ≥ 30 mg/dl and presence of femoral plaque were identified as independent predictors of coronary atherosclerosis. Conclusion Subclinical atherosclerosis is prevalent among FH patients, and this study has identified independent predictors associated with presence of subclinical atherosclerosis. However, despite this heightened risk, medication utilization among these patients remains below optimal levels and only a small proportion of the population has achieved their treatment goals. Our study highlights the influence of subclinical atherosclerosis on treatment approaches, as demonstrated by the notable rise in statin and aspirin utilization observed after screening.Clinical and biochemical characteristicsSubclinical Atherosclerosis Rates

Influence of coronary plaque characteristics on lesion-specific ischemia assessed by coronary computed tomography angiography and fractional flow reserve - a systematic review and meta-analysis

Abstract Background Characterization of atherosclerotic plaque features by coronary computed tomography angiography (CCTA) carries profound prognostic value. Previous studies indicate that coronary plaque burden and certain plaque features are associated to lesion-specific ischemia by invasive fractional flow reserve (FFR). However, the existing literature is limited by small sample sizes, and provide inconsistent results. Purpose We performed a meta-analysis in order to delineate further the potential association between coronary plaque phenotype by CCTA and FFR. Methods A comprehensive systematic literature review and meta-analysis was conducted. PubMed and Embase databases were searched for studies that investigated the association between coronary plaque characteristics and FFR between January 2010 and August 2023. Study search, evaluation, and data extraction were performed independently by two researchers. Weighted mean difference (WMD) method for WMD was used for comparison of pooled per-lesion plaque parameters and presence of specific plaque features against presence of lesion-specific ischemia (FFR ≤0.80). Lesions with stenosis severity of 25-90% were included. Extracted data from eligible studies were analysed using random effects model for WMD and to estimate odds ratios (OR) with 95% confidence intervals (CI). Results A total of 12 studies were deemed eligible with 1,318 patients and available data on 1,915 coronary lesions. Of these, 626 lesions caused ischemia. Significantly greater total plaque volume (TPV) and non-calcified plaque volume (NCPV) occurred in lesions with abnormal FFR compared to normal FFR (WMD 83.0 mm3, 95% CI: 44.27; 121.81, p<0.001; WMD 83.63 mm3, 95% CI: 55.0; 112.24, p <0.001, respectively). Similar findings were observed for aggregate plaque volume (%APV) and plaque burden (%PB) with WMD 9.18, 95% CI: 6.08; 12.28, p<0.001; WMD 8.83, 95% CI: 4.32; 14.24, p=0.001, respectively. Napkin ring-sign and spotty calcification appeared more frequent in ischemia-causing lesions compared to those with FFR >0.80 (OR 4.25, 95% CI: 1.39; 13.00, p=0.011; OR 1.92, 95% CI: 1.33; 2.75, p=0.001, respectively). A summary of the meta-analysis findings regarding the association between plaque burden and plaque characteristics and FFR is provided in Figure 1 and 2. Conclusion CCTA-derived TPV and NCPV as well as %APV, %PB and the presence of napkin-ring sign and spotty calcification are associated with presence of lesion-specific ischemia. Coronary plaque assessment from CCTA images provide improved discrimination of lesion-specific ischaemia.

Analysis of risk factors for carotid artery plaque in asymptomatic adults

ObjectiveThis study aimed to investigate the risk factors affecting the presence of carotid plaque in asymptomatic adults.MethodsAsymptomatic adults (age > 40 years, no symptoms of cardiovascular and cerebrovascular diseases) undergoing routine health examinations from physical examination department were included in this study. Carotid plaque was measured by Resona 7OB and Resona 8EXP color Doppler ultrasound and L9-3U and L4-5WU probes. The focal carotid intima–media thickness was greater than 1.1 mm, and the local protrusion of the artery wall into the artery lumen suggested the presence of carotid atherosclerotic plaque. According to their ultrasound results, 1077 asymptomatic adults were divided into a group with carotid plaque (477) and a group without carotid plaque (600).ResultsA total of 1077 asymptomatic adults were included in this study, of whom 44.3% had carotid plaque. The proportion of men with carotid plaque was 84.5%. Multifactorial logistic analysis suggested that age, fasting blood glucose (FBG), total cholesterol (TC), homocysteine (Hcy) and male gender were risk factors for carotid atherosclerosis. The predictive probability of these risk factor indicators derived from the multifactorial model was calculated using receiver operating characteristic (ROC) curves with SPSS 25.0 software. The calculated area under the receiver operating characteristic curve (AUC) was 0.715 (95% CI, 0.685–0.746).ConclusionAge, FBG, TC, Hcy and male gender are risk factors for carotid atherosclerosis in asymptomatic adults. Gender differences in carotid atherosclerosis deserve further attention.

Regular cannabis smoking and carotid artery calcification in the Multi-Ethnic Study of Atherosclerosis (MESA).

Studies on cannabis use and adverse cardiovascular outcomes have reported conflicting results. Research on its relationship to calcified arterial plaque remains limited. Cross-sectional data from 2152 participants at Exam 6 (2016-2018) in the Multi-Ethnic Study of Atherosclerosis (MESA) were analyzed, including self-reported cannabis smoking patterns and carotid artery calcification (CAC) as measured via computed tomography. Multivariable relative and absolute risk regression models were used to estimate adjusted prevalence ratios (PRs) and prevalence differences, respectively, for the presence of calcified plaque. Multivariable linear regression was then used to compare group differences in the extent of CAC in those with calcified plaque. A minority of participants (n = 159, 7.4%) reported a history of regular cannabis smoking. Among all participants, 36.1% (n = 777) had detectable CAC. In models adjusted for demographics, behavioral, and clinical cardiovascular disease factors, a history of regular cannabis smoking was not associated with the prevalence of CAC in either common carotid artery (PR: 1.14, 95% CI: 0.88 to 1.49). In the subset of participants with calcified plaque, and in separate fully adjusted multivariable linear regression models, a history of regular cannabis smoking was not associated with increased calcium volume (difference = 7.7%, 95% CI: -21.8 to 48.5), calcium density (difference = 0.4%, 95% CI: -6.6 to 7.9), or Agatston score (difference = 32.1%, 95% CI: -31.8 to 155.8) in either carotid artery. Models exploring potential effect modification by age, race/ethnicity, and tobacco smoking status showed no significant association, except for higher CAC prevalence in men with a history of regular cannabis smoking. In a racially and ethnically diverse cohort of older adults with a moderately high prevalence of CAC, no associations were found between a history of regular cannabis smoking, duration, or recency of cannabis smoking, and the prevalence of carotid calcified plaque. These findings were consistent across age, race/ethnicity, and cigarette smoking, except for an increased prevalence in men with a history of regular cannabis smoking. Similarly, in a subgroup with CAC, no association was found between a history of regular cannabis smoking and extent of calcification as measured by volume, density, and Agatston score.

Effectiveness of nonsurgical re-instrumentation: Tooth-related factors.

To investigate tooth-related factors that influence pocket closure (PC) and the reduction of pocket probing depths (PPD) after nonsurgical re-instrumentation (NSRI) as part of step 3 therapy. A total of 480 patients (10,807 teeth) presenting with residual pockets 6.33±3.79 months after steps 1 and 2 of periodontal therapy were included and retrospectively analyzed before and 5.93±4.31 months after NSRI. Reduction of PPD and PC rates following NSRI were associated with tooth-related factors, namely tooth type, arch, number of roots, furcation involvement (FI), pulp vitality, mobility, type of restoration, presence of plaque, and bleeding on probing (BOP), using mixed-effects regression models. NSRI reduced periodontal pockets persisting after initial cause-related therapy by (mean±SD) 1.32±1.79mm in PPD, and PC rate was 40%. Moderate pockets (4-5mm) responded better to NSRI than deep pockets (≥6mm) in terms of PC (51% vs. 16%). Both PPD reduction and PC rates of deep residual pockets were significantly influenced by tooth type, arch, number of roots, and presence of BOP. Tooth type, arch, number of roots, and presence of BOP at re-evaluation (before NSRI) had a significant and clinically relevant influence on NSRI as part of step 3 therapy. Considering these factors, particularly for deep residual pockets, may allow more tailored re-intervention. The present study aimed to investigate the influence of tooth-related factors on the outcome of repeated nonsurgical therapy of periodontitis. Therefore, 480 patients (10,807 teeth) presenting with clinical symptoms of persistent periodontitis after initial therapy were administered repeated nonsurgical therapy and retrospectively analyzed. Therapy outcomes were associated with tooth-related factors, namely tooth type, tooth location (maxilla/mandible), number of roots, involvement of the root furcation area in multi-rooted teeth, pulp vitality, mobility, restoration, presence of plaque and bleeding upon periodontal probing, using mixed-effects models. The results revealed that repeated nonsurgical therapy was effective in reducing inflammation and clinical signs of disease, with moderate residual periodontal defects responding better than deep defects. Healing of deep defects after repeated nonsurgical therapy; however, was significantly influenced by the factors: tooth type, location, number of roots, and bleeding on probing. Considering these factors, particularly in deep residual defects which are commonly suggested to be treated surgically, may allow less invasiveness and thus a more tailored re-intervention.

Associations between inflammatory markers and carotid plaques in CKD: mediating effects of eGFR–a cross-sectional study

BackgroundChronic kidney disease (CKD) is a significant public health concern associated with a high prevalence of carotid plaques, which are indicators of atherosclerosis and predictors of adverse cardiovascular outcomes. Inflammation is a hallmark of CKD, contributing to both renal dysfunction and cardiovascular complications. This study aims to investigate the association between inflammatory markers—systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), aggregate inflammatory status index (AISI), monocyte to high-density lipoprotein cholesterol ratio (MHR), neutrophil to high-density lipoprotein cholesterol ratio (NHR), neutrophil to lymphocyte ratio (NLR), and monocyte to lymphocyte ratio (MLR)—and carotid plaques in CKD patients, and to explore the potential mediating role of estimated glomerular filtration rate (eGFR) in this relationship.MethodsA cross-sectional analysis was conducted on patients admitted to the Division of Nephrology between January 2023 and June 2023. The primary endpoint was the presence of carotid plaques assessed using ultrasound imaging. Multivariable logistic regression models were used to examine the associations between inflammatory markers and carotid plaques, and trend tests were performed to evaluate the trending association of carotid plaques risk and inflammatory markers in tertiles. Restricted cubic spline (RCS) analysis was used to assess potential non-linear relationships, and subgroup analyses were conducted to examine consistency across different strata. Mediation analysis was performed to explore the role of eGFR.ResultsOf the 609 participants, 387 were included in the final analysis after applying exclusion criteria. Elevated levels of LnSIRI (OR = 1.87, 95% CI = 1.25–2.80), LnSII (OR = 1.67, 95% CI = 1.09–2.56), LnAISI (OR = 1.70, 95% CI = 1.22–2.37), LnMHR (OR = 1.94, 95% CI = 1.15–3.26), LnNHR (OR = 1.82, 95% CI = 1.10–3.02), and LnMLR (OR = 2.26, 95% CI = 1.18–4.34) were significantly associated with the presence of carotid plaques. There were significant trends for increasing tertiles of SIRI, AISI, MHR and NHR. RCS analysis showed no significant non-linear associations. Subgroup analyses indicated similar associations across most strata. eGFR partially mediated these relationships, with proportions mediated ranging from 14.7 to 17.5%.ConclusionsInflammatory markers are significantly associated with carotid plaques in CKD patients, with eGFR playing a partial mediating role. These findings highlighted the importance of managing inflammation and maintaining renal function to mitigate the risk of atherosclerosis in CKD patients.Trial registrationNot applicable.

Serum Level of Cadherin-P (CDH3) Is a Novel Predictor of Cardiovascular Events Related to Atherosclerosis in a 3-Year Follow-Up Study

Background: Placental cadherin (CDH3) is an adhesion molecule expressed in many malignant tumors. The role of serum CDH3 in atherosclerosis is unclear. Methods: This 3-year follow-up study measured atherosclerosis and serum CDH3 in 218 angiography inpatients. Coronary stenosis was assessed as the Gensini score. The brachiocephalic and femoral plaques were quantified by ultrasound. Microarray serum profiling was conducted in selected samples. CDH3 in the serum was measured using an indirect ELISA. The odds ratio (OR), ROC analysis, and logistic regressions were used to evaluate the associations between CDH3 content, atherosclerotic lesions, and various serum biomarkers. Results: Serum CDH3 was associated with the severity of atherosclerosis and diastolic blood pressure. The levels of CDH3 were able to discriminate patients with total subclinical and hemodynamically significant atherosclerotic lesions in all circulation pools (coronary, brachiocephalic, and femoral). Elevated serum CDH3 appeared to be a risk factor for cardiovascular outcomes after 3-year follow up with OR = 1.81 (95% CI: 1.07–3.72; p = 0.022). Endothelin-1 and NOx were associated with the content of CDH3 in the serum, suggesting the involvement of certain signal transduction pathways that may participate in plaque formation. Conclusions: CDH3 was associated with cardiovascular outcomes adjusted for coronary plaque presence, indicating a role of CDH3 in plaque biology.

Rare Clinical Presentation of Breast Cancer Metastasis: Carcinoma in Cuirasse

Breast cancer metastases in the skin can have different clinical presentations, breast carcinoma in armor has an exceptional presentation. It is called "cuirasse carcinoma" because of its resemblance to the armor of cavalry soldiers, it is characterized by the presence of erythematous plaques of fibrous consistency that can become ulcerated, on the skin of the thorax. It usually appears between 60 and 80 years of age, as a first sign or as part of metastasis. When associated with metastasis, it is associated with a history of chemotherapy, radiotherapy or mastectomy. Treatment can be given with electro-chemotherapy, photodynamic therapy, intra-lesional therapy, hormonal therapy and local therapy with the aim of palliating the disease.

Evaluation of oral and dental health parameters in children with special care needs

AIM. The aim of this study is to evaluate and raise awareness of the oral and dental health parameters in children aged 6 to 16 years with special care needs who are enrolled in special education institutions located in the central districts of Diyarbakir in Turkey. Specifically, the study examines the presence of caries, plaque, malocclusions, and molar-incisor hypomineralization.METHODS. A total of 368 children with special care needs participated in the study, with ages ranging from 6 to 16 years and an average age of 9.61 years. Of the participants, 196 have intellectual disabilities, 51 have Down syndrome, and 121 have autism spectrum disorder. The clinical findings of our study include the DMFT/dmft index, plaque index, occlusal relationships, and the presence of molar-incisor hypomineralization (MIH). The data obtained were analyzed using the SPSS v21 software package.RESULTS. The mean DMFT/dmft value was found to be 5.64, and the mean plaque index value was 1.37. The occlusal relationships of the participants were as followed: 78.26% had Class I, 11.14% had Class II, and 10.6% had Class III. Additionally, 98.64% of the participants did not have molar-incisor hypomineralization (MIH), while 1.36% did have MIH.CONCLUSION. In our study, it was found that children with special care needs generally have poor oral hygiene, their parents/caregivers lack sufficient awareness, and the prevalence of caries and plaque index is high in the examined population.

Including educational status may improve cardiovascular risk calculations such as SCORE2.

The association between education and atherosclerotic cardiovascular disease (ASCVD) has been well described for decades. Nevertheless, most cardiovascular risk models, including SCORE2, still do not take educational status into account even if this factor is easily assessed and costs nothing to acquire. Using carotid plaques as a proxy for ASCVD, we analysed educational status as associated with carotid plaque development, to determine if the relationship remains, how it relates to traditional risk factors and, how it impacts the European cardiovascular risk model, SCORE2. Our study also provides further data on plaque development in a well-characterised population nearly equally weighted by gender. 9,083 subjects (51% female, 49% male) from the Paracelsus 10,000 cohort, underwent a carotid doppler duplex as part of thorough screening for subclinical ASCVD. Well over 90% of carotid doppler duplex examinations were performed by the same experienced clinician. Subjects were then classified by educational status using the Generalized International Standard Classification of Education. Plaque absence or presence was dichotomised and variables analysed using regression modelling to examine educational status relative to cardiovascular risk factors and with respect to the SCORE2 model. Using medium educational status as a reference, subjects in our cohort with low educational status had higher odds, while subjects with high educational status had lower odds for carotid plaques compared to subjects with medium education (aOR 1.76 95%CI 1.50-2.06; and 0.0.63 95%CI 0.57-0.70, respectively). Even after adjusting for common risk factors including metabolic syndrome and SCORE2, the relationship was maintained. Furthermore, when comparing the potential predictive power of SCORE2 alone and plus educational status using the Akaike information criterion, we showed a 'better fit' when educational status was added. Measuring educational status is cost-free and easy for clinicians to obtain. We believe cardiovascular risk prediction models such as SCORE2 may more accurately reflect individual risk if educational status is also taken into account. Additionally, we believe clinicians need to understand and appropriately address educational status as a risk factor, to better quantify individual risk and take appropriate measures to reduce risk so that the association may finally be broken.

Interaction of a self-expandable stent with the arterial wall in the presence of hypocellular and calcified plaques.

Self-expandable stents manufactured from nitinol alloys are commonly utilized alongside traditional balloon-expandable stents to provide scaffolding to stenosed arteries. However, a significant limitation hampering stent efficacy is restenosis, triggered by neointimal hyperplasia and resulting in the loss of gain in lumen size, post-intervention. In this study, a nonlinear finite element model was developed to simulate stent crimping and expansion and its interaction with the surrounding vessel in the presence of a plaque. The main aim was to determine contact pressures and forces induced at the interface between an artery wall with hypocellular and calcified plaques and an expanded stent. The results demonstrated the drawbacks of plaque calcification, which triggered a sharp contact pressure and radial force surge at the interface as well as a significant rise in von Mises stress within the vessel, potentially leading to rupture and restenosis. A regression line was then established to relate hypocellular and calcified plaques. The adjusted coefficient of determination indicated a good correlation between contact pressures for calcified and hypocellular plaque models. Regarding the directionality of wall properties, contact pressure and force observations were not significantly different between isotropic and anisotropic arteries. Moreover, variations in friction coefficients did not substantially affect the interfacial contact pressures.