Progression Of Atherosclerosis In Patients Research Articles

An Evaluation of Plasma TNF, VEGF-A, and IL-6 Determination as a Risk Marker of Atherosclerotic Vascular Damage in Early-Onset CAD Patients.

Background: The pathogenesis of atherosclerosis is multifactorial and diverse. Pro-inflammatory cytokines are involved in these processes. It is suggested that inflammation may represent a novel and modifiable risk factor for cardiovascular disease. Therefore, this study aimed to gain insight into the relationship between plasma concentrations of TNF, VEGF, IL-6, and radiological parameters of atherosclerosis progression in patients with early-onset coronary artery disease (CAD). Methods: Seventy clinically stable patients were included in the study group. The age range for men was no more than 50 years, while for women, it was no more than 55 years. Fasting blood samples were obtained for plasma TNF, VEGF, and IL-6 protein measurements. Plasma cytokine concentrations were measured via ELISA. Doppler ultrasound of the carotid and peripheral arteries was performed in all patients. Results: After Bonferroni correction, there were no significant correlations between any cytokine and radiological parameters of atherosclerosis progression in our patients. Conclusions: The determination of plasma TNF, IL-6, and VEGF levels may not be a reliable marker for the vascular condition, and the measurement of these cytokines in plasma cannot replace the classical radiological examination of the vessels.

Pro-Inflammatory Biomarkers and Progression of Atherosclerosis in Patients with Myocardial Infarction with Non-Obstructive Coronary Artery Disease: 1-Year Follow-Up.

Samples of peripheral venous blood were collected upon admission and on days 2, 4, and 7 of hospitalization and after 1 year. An extended multiplex analysis was performed in blood serum. Multidetector-computed tomography coronary angiography was performed on day 7 and 1 year after acute myocardial infarction to assess the progression of atherosclerosis. The level of high-sensitive C-reactive protein (hsCRP) was elevated upon admission in MINOCA patients compared to MI-CAD patients (p = 0.05), but it was comparable in two groups at other time points and did not exceed the reference range after 1 year. Despite comparable levels of cytokines CXCL-6, LIGHT, CCL-8, and endocan-1 in patients in both groups, MINOCA patients had a greater increase in pro-inflammatory cytokines PlGF, oncostatin M, IL-20, and CCL-15 sVCAM-1 in the early post-infarction period and in CCL-21, sVCAM-1, oncostatin M, and PlGF after 1 year. We observed significant differences in the dynamics of the following biomarkers between patients with MI-CAD and MINOCA: the dynamics of concentrations of CCL21 (p = 0.002), LIGHT (p = 0.03), and endocan-1 (p = 0.03) after 1 year compared to day 1 in MI-CAD and MINOCA patients was opposite, while the dynamics of CXCL6 (p = 0.04) and endocan-1 (p = 0.02) differed between groups when evaluated after 1 year compared to day 7 of the early post-infarction period. In the MINOCA group, factors associated with atherosclerosis progression were concentrations of sVCAM-1 and CCL-21, while in the MI-CAD group, concentrations of CCL-8 and CXCL6 were the main determinants of atherosclerosis progression. This small study showed that MINOCA and MI-CAD patients exhibited differences in a pro-inflammatory biomarker profile in the early post-infarction period and after 1-year follow-up, which implies distinct inflammatory pathways involved in atherogenesis during MINOCA. The key factors that were associated with atherosclerosis progression in MINOCA patients are sVCAM-1 and CCL-21, which may suggest a complex genesis of atherosclerosis progression due to structurally altered plaques and changes in the microcirculatory bed. In MI-CAD patients, CCL-8 and CXCL-6 were the key biomarkers associated with atherosclerosis progression. Further large-scale studies are required to confirm our data.

Effects of long term antiseizure medications on atherosclerosis

Long-term therapy with antiseizure medications (ASMs) has been associated with metabolic consequences that lead to an increase in the risk of atherosclerosis in patients with epilepsy. This study was conducted to assess the effects of ASMs on vascular risk factors namely, serum Lipid profile and C-reactive protein (CRP) in epileptic patients and to assess the correlation between the duration of the ASMs, and carotid intima media thickness (IMT). Forty three adult patient participants who were receiving ASM monotherapy for more than 2 years and 43 control patients were enrolled in this study. All participants received measurement of common carotid artery (CCA) and IMT by B-mode ultrasonography to assess the extent of atherosclerosis. Other measurements included body mass index (BMI), serum lipid profile and CRP. The correlation between duration of ASM and average carotid IMT was calculated by using the Pearson's correlation coefficient method. The majority of subjects on phenytoin 8 (66.7%) were positive for CRP. There was an equal proportion of patients on carbamazepine who were equally positive 5(50%) and negative 5(50%) for CRP. There was a statistically significant association between phenytoin consumption and CRP positivity. There was positive correlation between duration of phenytoin consumption and average IMT. There was a strong positive correlation between duration of phenobarbitone consumption and average IMT and was statistically significant. Our results also suggest that long-term use of ASMs with prominent effects on the enzyme system, including Carbamazepine, phenytoin, sodium valproate or phenobarbitone may contribute to the progression of atherosclerosis in patients with epilepsy. Keywords: epilepsy; ASMs; IMT; CRP; phenytoin; carbamazepine; sodium valproate; phenobarbitone

Progression of non-obstructive coronary plaque: a practical CCTA-based risk score from the PARADIGM registry.

No clear recommendations are endorsed by the different scientific societies on the clinical use of repeat coronary computed tomography angiography (CCTA) in patients with non-obstructive coronary artery disease (CAD). This study aimed to develop and validate a practical CCTA risk score to predict medium-term disease progression in patients at a low-to-intermediate probability of CAD. Patients were part of the Progression of AtheRosclerotic PlAque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry. Specifically, 370 (derivation cohort) and 219 (validation cohort) patients with two repeat, clinically indicated CCTA scans, non-obstructive CAD, and absence of high-risk plaque (≥ 2 high-risk features) at baseline CCTA were included. Disease progression was defined as the new occurrence of ≥ 50% stenosis and/or high-risk plaque at follow-up CCTA. In the derivation cohort, 104 (28%) patients experienced disease progression. The median time interval between the two CCTAs was 3.3years (2.7-4.8). Odds ratios for disease progression derived from multivariable logistic regression were as follows: 4.59 (95% confidence interval: 1.69-12.48) for the number of plaques with spotty calcification, 3.73 (1.46-9.52) for the number of plaques with low attenuation component, 2.71 (1.62-4.50) for 25-49% stenosis severity, 1.47 (1.17-1.84) for the number of bifurcation plaques, and 1.21 (1.02-1.42) for the time between the two CCTAs. The C-statistics of the model were 0.732 (0.676-0.788) and 0.668 (0.583-0.752) in the derivation and validation cohorts, respectively. The new CCTA-based risk score is a simple and practical tool that can predict mid-term CAD progression in patients with known non-obstructive CAD. The clinical implementation of this new CCTA-based risk score can help promote the management of patients with non-obstructive coronary disease in terms of timing of imaging follow-up and therapeutic strategies. • No recommendations are available on the use of repeat CCTA in patients with non-obstructive CAD. • This new CCTA score predicts mid-term CAD progression in patients with non-obstructive stenosis at baseline. • This new CCTA score can help guide the clinical management of patients with non-obstructive CAD.

Impact of immune checkpoint inhibitors on atherosclerosis progression in patients with lung cancer

BackgroundPatients with lung cancer face a heightened risk of atherosclerosis-related cardiovascular events. Despite the strong scientific rationale, there is currently a lack of clinical evidence examining the impact of immune...

Dietary modulation of advanced glycation end products metabolism on carotid intima-media thickness in type 2 diabetes patients: From the CORDIOPREV study

BackgroundAdvanced glycation end products (AGEs) are pro-oxidant and cytotoxic compounds involved in the progression of chronic diseases as cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The total body burden of AGEs also depend of those consume through the diet. Our aim was to analyze whether the reduction of AGE levels, after the consumption of two-healthy diets were associated with a greater decrease of intima-media thickness of both common carotid arteries (IMT-CC) in patients with T2DM and coronary heart disease (CHD). Methods540 CHD patients with T2DM, at baseline, from the CORDIOPREV study, were divided into two groups: (1) Responders, patients whose IMT-CC was reduced or not changed after dietary intervention and (2) Non-responders, patients whose IMT-CC was increased after dietary intervention. A total of 423 completed baseline and the 5-year follow-up carotid ultrasounds were analyzed in this study. ResultsOur data showed that Responders, despite had a higher baseline IMT-CC and serum methylglyoxal (MG) levels than Non-responders, showed a reduction of serum levels of this glycotoxin after dietary intervention. Conversely, in patients whose IMT-CC was increased after dietary intervention (Non-responders), serum MG levels were increased. Moreover, an increase of circulating level of AGEs (and in particular, MG), after dietary intervention, could be considered a risk factor for the progression of atherosclerosis in patients with T2DM and CHD. ConclusionThese results support the importance of identifying underlying mechanisms in the context of secondary prevention of CVD that would provide therapeutic targets to reduce the high risk of cardiovascular events of these patients.Clinical Trial registration-URL: https://clinicaltrials.gov/ct2/show/NCT00924937.Unique Identifier: NCT00924937.

Effect of liraglutide on atherosclerosis in patients with impaired glucose tolerance: A double‑blind, randomized controlled clinical trial.

Glucagon-like peptide-1 receptor agonist liraglutide may have beneficial effects on atherosclerosis development in impaired glucose tolerance (IGT). To the best of our knowledge, however, little conclusive evidence from clinical trials has been presented. The present study aimed to investigate the effect of liraglutide on atherosclerosis progression in patients with IGT. The present study was a double-blind, randomized controlled clinical trial. A total of 39 of patients aged 20-75 years who were overweight or obese (BMI, 27-40 kg/m2) and presented IGT were randomized to receive liraglutide (n=17) or lifestyle interventions (n=22) for 6 months. Serum glucose and insulin (INS) levels, lipid profile, inflammatory biomarkers and carotid intima-media thickness (CIMT) were assessed at the start and end of each treatment. Side effects were also recorded. Liraglutide treatment was found to significantly improve glycaemia, including glycosylated hemoglobin, fasting and postprandial glucose as well as INS levels (all P<0.001). Liraglutide also significantly decreased serum total cholesterol and low-density lipoprotein levels (all P<0.001). Furthermore, serum levels of inflammatory biomarkers, as well as CIMT, were decreased following liraglutide treatment compared with those in the lifestyle intervention group (all P<0.001). Kaplan-Meier analysis showed that the risk of vasculopathy in the liraglutide group was lower than that in the lifestyle intervention group (log-rank test; P=0.041). The monitoring of drug-associated side effects indicated that the dose of liraglutide (0.6 to 1.2 mg/QD via subcutaneous injection) was safe and well-tolerated. The present study suggested that liraglutide may slow atherosclerosis development and improve inflammatory status as well as intimal function in patients with IGT with few side effects. The trial was registered through the Chinese Clinical Trial Registry (ChiCTR; trial registration no. ChiCTR2200063693; retrospectively registered) on Sep 14, 2022.

Clinical and Coronary Plaque Predictors of Atherosclerotic Nonresponse to Statin Therapy

BackgroundStatins reduce the incidence of major cardiovascular events, but residual risk remains. The study examined the determinants of atherosclerotic statin nonresponse. ObjectivesThis study aimed to investigate factors associated with statin nonresponse-defined atherosclerosis progression in patients treated with statins. MethodsThe multicenter PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging) registry included patients who underwent serial coronary computed tomography angiography ≥2 years apart, with whole-heart coronary tree quantification of vessel, lumen, and plaque, and matching of baseline and follow-up coronary segments and lesions. Patients with statin use at baseline and follow-up coronary computed tomography angiography were included. Atherosclerotic statin nonresponse was defined as an absolute increase in percent atheroma volume (PAV) of 1.0% or more per year. Furthermore, a secondary endpoint was defined by the additional requirement of progression of low-attenuation plaque or fibro-fatty plaque. ResultsThe authors included 649 patients (age 62.0 ± 9.0 years, 63.5% male) on statin therapy and 205 (31.5%) experienced atherosclerotic statin nonresponse. Age, diabetes, hypertension, and all atherosclerotic plaque features measured at baseline scan (high-risk plaque [HRP] features, calcified and noncalcified PAV, and lumen volume) were significantly different between patients with and without atherosclerotic statin nonresponse, whereas only diabetes, number of HRP features, and noncalcified and calcified PAV were independently associated with atherosclerotic statin nonresponse (odds ratio [OR]: 1.41 [95% CI: 0.95-2.11], OR: 1.15 [95% CI: 1.09-1.21], OR: 1.06 [95% CI: 1.02-1.10], OR: 1.07 [95% CI: 1.03-1.12], respectively). For the secondary endpoint (N = 125, 19.2%), only noncalcified PAV and number of HRP features were the independent determinants (OR: 1.08 [95% CI: 1.03-1.13] and OR: 1.21 [95% CI: 1.06-1.21], respectively). ConclusionsIn patients treated with statins, baseline plaque characterization by plaque burden and HRP is associated with atherosclerotic statin nonresponse. Patients with the highest plaque burden including HRP were at highest risk for plaque progression, despite statin therapy. These patients may need additional therapies for further risk reduction.

Dietary modulation of advanced glycation end products metabolism on carotid intima-media thickness in type 2 diabetes patients: From the CORDIOPREV study

BackgroundAdvanced glycation end products (AGEs) are pro-oxidant and cytotoxic compounds involved in the progression of chronic diseases as cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The total body burden of AGEs also depend of those consume through the diet. Our aim was to analyze whether the reduction of AGE levels, after the consumption of two-healthy diets were associated with a greater decrease of intima-media thickness of both common carotid arteries (IMT-CC) in patients with T2DM and coronary heart disease (CHD). Methods540 CHD patients with T2DM, at baseline, from the CORDIOPREV study, were divided into two groups: (1) Responders, patients whose IMT-CC was reduced or not changed after dietary intervention and (2) Non-responders, patients whose IMT-CC was increased after dietary intervention. A total of 423 completed baseline and the 5-year follow-up carotid ultrasounds were analyzed in this study. ResultsOur data showed that Responders, despite had a higher baseline IMT-CC and serum methylglyoxal (MG) levels than Non-responders, showed a reduction of serum levels of this glycotoxin after dietary intervention. Conversely, in patients whose IMT-CC was increased after dietary intervention (Non-responders), serum MG levels were increased. Moreover, an increase of circulating level of AGEs (and in particular, MG), after dietary intervention, could be considered a risk factor for the progression of atherosclerosis in patients with T2DM and CHD. ConclusionThese results support the importance of identifying underlying mechanisms in the context of secondary prevention of CVD that would provide therapeutic targets to reduce the high risk of cardiovascular events of these patients.Clinical Trial registration-URL: https://clinicaltrials.gov/ct2/show/NCT00924937.Unique Identifier: NCT00924937.

Correlation of monomeric C-reactive protein level with subclinical carotid atherosclerosis progression in patients with low-grade carotid stenoses and moderate score risk

Background and Aims : Residual inflammatory risk is identified by hsCRP level ≥2.0 mg/l. Monomeric CRP (mCRP) is an emerging inflammatory biomarker. We studied whether mCRP level is a better predictor of carotid atherosclerosis (CA) progression than hsCRP in patients with low-grade CA and moderate SCORE risk which achieved target LDL cholesterol (LDL-C) level.

Progerin-Induced Impairment in Wound Healing and Proliferation in Vascular Endothelial Cells

Progerin as a mutated isoform of lamin A protein was first known to induce premature atherosclerosis progression in patients with Hutchinson-Gilford progeria syndrome (HGPS), and its role in provoking an inflammatory response in vascular cells and accelerating cell senescence has been investigated recently. However, how progerin triggers endothelial dysfunction that often occurs at the early stage of atherosclerosis in a mechanical environment has not been studied intensively. Here, we generated a stable endothelial cell line that expressed progerin and examined its effects on endothelial wound repair under laminar flow. We found decreased wound healing rate in progerin-expressing ECs under higher shear stress compared with those under low shear. Furthermore, the decreased wound recovery could be due to reduced number of cells at late mitosis, suggesting potential interference by progerin with endothelial proliferation. These findings provided insights into how progerin affects endothelial mechanotransduction and may contribute to the disruption of endothelial integrity in HGPS vasculature, as we continue to examine the mechanistic effect of progerin in shear-induced endothelial functions.

Coronary atherosclerosis progression in patients after coronary stenting, depending on a cardiology follow-up strategy

Aim. To compare the prevalence of coronary atherosclerosis in patients after coronary stenting (CS) receiving outpatient and remote cardiology follow-up during a one-year study.Material and methods. We enrolled 279 patients aged 61,5±9,5 years with class ≥II stable angina or silent ischemia after CS. Three groups were formed: group 1 (n=96) — outpatient visits before CS, 1, 3, 6 and 12 months after CS. Group 2 (n=95) — remote monitoring: patients were followed up by a primary care physician with the involvement of a cardiologist via remote communication (e-mail, telephone, Skype) 1, 3, 6 and 12 months after CS. Group 3 (n=88) were followed up by a primary care physician and contacted with the study coordinator before and 12 months after CS. After 12 months, all patients underwent stress-induced myocardial ischemia testing. In case of a positive or uncertain test result, coronary angiography (CA) was performed.Results. Stress-induced myocardial ischemia 12 months after CS was verified in 58 patients (21%): 19 patients (19,8%) — group 1; 9 patients (9,5%) — group 2; 30 patients (34,1%) — group 3 (p&lt;0,05). Repeat CA was performed in 96 patients (34,4% of the total number of patients). Restenosis was detected in 8 (2,9%) patients, coronary atherosclerosis progression — in 38 (13,6%), combination of restenosis and atherosclerosis progression — in 4 (1,4%) patients. Coronary atherosclerosis progression was significantly more frequent in group 3: 10,4%, 9,5% and 21,6% in groups 1, 2 and 3, respectively (p&lt;0,05). The incidence of stent restenosis was comparable: 2,1%, 3,2% and 3,5% in groups 1, 2, and 3, respectively.Conclusion. Coronary atherosclerosis progression was the main reason for repeated revascularizations 12 months after the CS. Outpatient and remote cardiology follow-up is associated with a lower incidence of coronary atherosclerosis progression and repeated CA during 12-month follow-up after CS.

Evaluation of the effect of tofogliflozin on the tissue characteristics of the carotid wall\u2014a sub-analysis of the UTOPIA trial

BackgroundSince sodium-glucose cotransporter 2 (SGLT2) inhibitors have a pleiotropic antiatherogenic effect, they are expected to attenuate the progression of atherosclerosis. However, whether SGLT2 inhibitors affect the tissue characteristics of the human arterial wall remains unclear. This study aimed to evaluate the effects of tofogliflozin, a selective SGLT2 inhibitor, on the tissue characteristics of the human arterial wall in type 2 diabetes (T2DM) patients without apparent cardiovascular disease (CVD).MethodsThe present study was a post hoc analysis based on data obtained from the Using Tofogliflozin for Possible Better Intervention against Atherosclerosis for Type 2 Diabetes Patients (UTOPIA) trial, which was a multicenter prospective, randomized, open-label, blinded-endpoint study conducted to evaluate the efficacy of tofogliflozin in preventing the progression of atherosclerosis in patients with T2DM. We evaluated the longitudinal change in the ultrasonic tissue characteristics of the carotid wall using gray-scale median (GSM), an established index of ultrasonic tissue characteristics. The right and left intima-medial areas were delineated, and the GSM values were evaluated (right GSM-CCA and left GSM-CCA). The average values of the right and left carotid arteries were defined as “mean GSM-CCA value.”ResultsIn a mixed-effects model for repeated measures, mean GSM-CCA, along with the right and left GSM-CCA values, did not significantly change in either the tofogliflozin (n = 168) or conventional treatment group (n = 169). In addition, the tofogliflozin and conventional treatment groups did not significantly differ regarding the change of the mean GSM-CCA (mean difference [95% CI] − 1.24[− 3.87, 1.38], P = 0.35), along with the right (mean difference [95% CI] − 2.33[− 5.70, 1.05], P = 0.18) and the left GSM-CCA (mean difference [95% CI] − 0.29 [− 3.53, 2.95], P = 0.86) values. Similar findings were obtained even after adjusting for traditional cardiovascular risk factors and/or the administration of drugs at baseline.ConclusionsThe tissue characteristics of the carotid arterial wall did not change in either the tofogliflozin or conventional treatment group during the 104-week treatment period, and there was no significant difference between the treatment groups.Clinical trial registration UMIN000017607 (https://www.umin.ac.jp/icdr/index.html)

New predictors of atherosclerosis progression after surgical interventions on the arteries of the lower extremities

BACKGROUNDː Thanks to experiments on animals, the influence of biomarkers of apoptosis, proliferation and endothelial dysfunction on the pathogenesis of atherosclerosis was proved. Aim: to identify the effect of these biomarkers on the progression of atherosclerosis in patients with peripheral arterial disease after surgery. METHODSː Patients were divided into two groups: A - 40 patients who have undergone endovascular interventions, B -38 patients, who have undergone hybrid surgery on the arteries of the lower extremities. Biomarkers Bax, sFas, PDGF BB, and nitric oxide (NO) were studied before intervention, on the 1st, 7th, 30th day after the operation. RESULTSː When comparing initial values of indicators and their values in the dynamics, the difference between group A and B was not found (p &gt; 0.05). Nine patients of group В developed progression of atherosclerosis after 17 months. Roc analysis showed that initial sFas ≤ 0,92 ng / ml, initial Вах ≥ 25,3 ng / ml, NO values ≤128.4 mmol / ml, sFas ≤ 0.645 ng / ml, Вах ≥ 33,8 ng / ml on the first postoperative day, and PDGF BB amount on the 7th day ≥ 28 ng / ml is associated with progression of atherosclerosis. CONCLUSIONSː The dynamics of biomarkers of apoptosis, proliferation and endothelium dysfunction in patients after endovascular and hybrid interventions did not differ significantly. The activation of two pathways markers of apoptosis against the background of reduced synthesis of NO leads to an enhanced proliferative response and is associated with progression of atherosclerosis after surgery.

NETosis in Long-Term Type 1 Diabetes Mellitus and Its Link to Coronary Artery Disease.

BackgroundNeutrophil extracellular traps NETs have been linked to glucose and the pathogenesis of type 1 diabetes mellitus (T1DM). NETs also play a role in vascular inflammation and the development of coronary artery disease (CAD). The role of NETs in CAD progression in patients with long-term T1DM is unclear. We aimed to 1) investigate whether levels of circulating NETs markers were elevated in long-term T1DM subjects compared to controls, and 2) explore whether levels of NETs were related to the presence of CAD.Material and Methods102 patients with > 45 years of T1DM and 75 age-matched controls were enrolled in a cross-sectional study. Median age was 62 years. Computed tomography coronary angiography (CTCA) was performed in 148 subjects without established coronary heart disease. For the current study, CAD was defined as a coronary artery stenosis >50%. Double-stranded deoxyribonucleic acid (dsDNA) was measured by a nucleic acid stain, myeloperoxidase-DNA (MPO-DNA), citrullinated histone 3 (H3Cit) and peptidylarginine deiminase 4 (PAD4) by ELISAs, while gene expression of PAD4 was measured in leukocytes from PAXgene tubes.ResultsCirculating MPO-DNA levels were significantly lower in patients with T1DM than in controls (0.17 vs 0.29 OD, p<0.001), while dsDNA, H3Cit, PAD4 and gene expression of PAD4 did not differ with respect to the presence of T1DM. There were no significant associations between NETs markers and HbA1c in the T1DM group. None of the NETs markers differed according to the presence of CAD in patients with T1DM. While all circulating NETs markers correlated significantly with circulating neutrophils in the control group (r=0.292-393, p<0.014), only H3Cit and PAD4 correlated with neutrophils in the T1DM group (r= 0.330-0.449, p ≤ 0.001).ConclusionsIn this cross-sectional study of patients with long-term T1DM and age-matched controls, circulating NETs levels were not consistently associated with the presence of T1DM or glycemic status, and did not differ according to the presence of CAD in patients with T1DM. Our results entail the possibility of altered neutrophil function and reduced NETosis in T1DM. This warrants further investigation.

[Leptin and leptin receptor evaluation in atherosclerotic plaques in patients with type 2 diabetes mellitus].

Diabetes mellitus (DM) is a significant predictor of atherosclerosis, cardiovascular disease, and cardiovascular mortality. It is known that atherosclerosis occurs earlier in patients with diabetes, reducing the duration of their life. Leptin as well as other inflammatory markers can contribute to the progression of atherosclerosis in patients with DM, participate in the development of a local inflammatory reaction. Determine the cells immunophenotype of atherosclerotic plaques in patients with diabetes. We analyzed 24 patients (20 men and 4 women), who underwent aortofemoral bypass, femoral-tibial bypass or carotid endarterectomy. During the operation, a fragment of the arterial wall with an atherosclerotic plaque was obtained for further immunohistochemical studies. Five histologic plaque characteristics (CD68+, -SMA, CD34, leptin and leptin receptor) were compared. No difference in the expression of CD68 (p=0.922), -SMA (p=0.192), CD34 (p=0.858), leptin receptor (p=0.741) and leptin (p=0.610) in atherosclerotic plaques were observed between patients with and without DM. The lack of significant differences between the two groups was possibly due to the small number of observations with DM. In particular, when assessing the expression of selected markers in atherosclerotic plaques, patients with DM showed significantly more leptin receptors than patients without DM (2160.716 and 1205.88 respectively); and also significantly less CD68+ (0.39 and 0.98 respectively) and -SMA+ (6.5 and 13.5 respectively). Based on the expression of CD68, -SMA, CD34, leptin receptor and leptin, no significant differences were observed in atherosclerotic plaque between patients with and without DM. At the same time, despite the limitations of the study (a small number of patients, moderate severity of DM, elderly patients in the DM group), we found a tendency in the increased number of leptin receptors and a decreased number of -SMA+, CD68+ in DM atherosclerotic plaques. Further study needed, taking into account the limitations of this work.

Vascular Protective Effects of New Oral Anticoagulants in Patients with Atrial Fibrillation.

This study was designed to determine the efficacy of a new oral anticoagulant (NOAC) therapy for the prevention of endothelial dysfunction and atherosclerosis progression in patients with atrial fibrillation (AF). Sixty-five AF patients with a CHA2DS2-VASc score ≥2 without previous history of cardiovascular disease were registered and randomly assigned to either an NOAC group (dabigatran or rivaroxaban) or the warfarin group. Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function were taken using Endo-PAT2000. Carotid intima–media thickness (IMT) was measured at baseline, 12 months, and 24 months, and several biomarkers were also analyzed. For the primary end point, the reactive hyperemia index (RHI) for the NOAC group was 1.5 ± 0.4 and that for the warfarin group was 1.6 ± 0.5. The left and right carotid IMT was 0.7 mm in the NOAC groups and 0.8 mm in the warfarin group. At 12 months, RHI was 1.6 ± 0.3 for the dabigatran group, 1.6 ± 0.5 for the rivaroxaban group, and 1.6 ± 0.3 for the warfarin group. The three groups did not differ statistically with respect to change in left and right carotid IMT at 12 and 24 months, respectively. The biomarkers for endothelial function and atherosclerosis were not significantly different. There was a trend of reduced P-selectin levels in the NOAC group compared to the warfarin group. In patients with AF, there were no significant differences in the prevention of endothelial dysfunction and atherosclerosis progression between the NOAC and warfarin groups.

Liver fibrosis is associated with carotid atherosclerosis in patients with liver biopsy-proven nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is related to subclinical atherosclerosis. However, whether the severity of the disease (or which histopathological component) is associated with subclinical atherosclerosis remains controversial. This study aimed to investigate the association between the histopathological severity of NAFLD and carotid intima-media thickness (CIMT) in Japanese patients with liver biopsy-proven NAFLD. Maximum-CIMT (max-CIMT) was measured as an index of carotid atherosclerosis in 195 biopsy-proven NAFLD patients. A significant association was observed between the severity of fibrosis (but not steatosis, inflammation, and ballooning) and max-CIMT. Older age, male gender, hypertension, and advanced fibrosis were independently linked to max-CIMT ≥ 1.2 mm. The prevalence of max-CIMT ≥ 1.2 mm was significantly higher in the advanced fibrosis group than in the non-advanced fibrosis group (75.4% versus 44.0%; p < 0.01). Non-invasive liver fibrosis markers and scoring systems, including fibrosis-4 index, NAFLD fibrosis score, hyaluronic acid, and Wisteria floribunda agglutinin positive Mac-2-binding protein, demonstrated that the diagnostic performance for max-CIMT ≥ 1.2 mm was similar to that of biopsy-based fibrosis staging. In conclusion, advanced fibrosis is significantly and independently associated with high-risk CIMT. Non-invasive fibrosis markers and scoring systems could help estimate the risk of atherosclerosis progression in patients with NAFLD.

Obesity May Not Be a Risk of Non-Target Lesion Revascularization in the Elderly Patients.

Obesity is assumed to be one of the robust risk factors for coronary artery disease. However, the effects of obesity on the progression of atherosclerosis in patients in different age groups after percutaneous coronary intervention (PCI) remain unclear. This study aimed to examine the effect of obesity on prognosis in different age groups.Consecutive patients who underwent urgent or elective PCI were surveyed for this study and were then divided into the elderly group and middle-aged group with a cut-off age of 70 years. All patients underwent coronary angiography or coronary computed tomography angiography 1 year after PCI to examine the progression of atherosclerosis. The primary endpoint was revascularization for a new lesion within 2 years after PCI. In addition, the main effects and correlations between obesity and age were examined. Multivariate logistic regression analysis was conducted to identify independent predictors of non-target lesion revascularization (non-TLR).Of the 711 patients who met the criteria and were available for follow-up analysis, the incidence of non-TLR within 2 years was 97/711 (13.6%). The higher incidence of non-TLR in patients with obesity was observed only in the middle-aged group. Furthermore, in the multivariate analysis, obesity was independently associated with non-TLR only in the middle-aged group.The findings of the present study would enable us to construct the hypothesis that obesity in elderly patients may not be an independent predictor of the incidence of non-TLR, indicating that the management to prevent non-TLR may vary depending on the age of the patient.

Potent platelet inhibition with peri-procedural tirofiban may attenuate progression of atherosclerosis in patients with acute coronary syndromes.

Organization of platelet-rich thrombus at the site of plaque disruption may contribute to rapid progression of atherosclerosis. This study was conducted to investigate if potent platelet inhibition therapy in patients with acute coronary syndromes (ACS) mitigates plaque progression. Patients enrolled in the EROSION study who presented with ACS caused by plaque erosion and underwent serial imaging of the culprit lesion by optical coherence tomography at baseline, 1month, and 1year were included. Among 49 patients, 32 (65.3%) patients were treated with glycoprotein IIb/IIIa inhibitor (GPI) in addition to aspirin and ticagrelor. The increase in area stenosis from baseline to 1-year follow-up was significantly smaller in patients treated with GPI, compared to those without GPI therapy (4.8% [- 1.6 to 10.9] vs. 9.6% [4.0 to 21.3], p = 0.031). The cohort was divided into 2 groups based on culprit lesion phenotype at 1year: Group A, new layer formation at 1-year that was not present at baseline (n = 18); Group B, no new layer formation (n = 31). A new layer was less frequently found at 1year in patients treated with GPI than in those without GPI (25.0% vs. 58.8%, p = 0.019). Group A, compared to Group B, was associated with a greater increase in area stenosis (19.0 ± 16.4% vs. 3.7 ± 7.1%; p < 0.001). Potent platelet inhibition with GPI in patients with ACS caused by plaque erosion was associated with lower incidence of new layer formation and less plaque progression.