Unstable Plaques In Patients Research Articles

Sodium-Glucose Cotransporter-2 Inhibitors Stabilize Coronary Plaques in Acute Coronary Syndrome With Diabetes Mellitus

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are widely used in cardiology and are effective in treating acute coronary syndrome (ACS). Their effects on unstable plaque in patients with ACS remains unclear. This study aimed to examine the effectiveness of SGLT2is in coronary plaque based on optical coherence tomography (OCT) images and the prognosis of ACS with type 2 diabetes mellitus. This retrospective study included 109 patients in the total cohort and 29 patients in the OCT cohort. Based on SGLT2i administration after ACS, the total cohort was categorized into non-SGLT2i (n = 69) and SGLT2i (n = 40) groups. The OCT cohort had 15 and 14 patients in the non-SGLT2i and SGLT2i groups, respectively. The OCT images of unstable plaque were analyzed in nonstented lesions during ACS catheterization and at the 6-month follow-up. The total cohort was assessed after 1 year for major adverse cardiovascular events, including all-cause mortality, revascularization, cerebrovascular disease, and heart failure hospitalization. SGLT2is improved unstable lesions with a significantly thicker fibrous cap (48 ± 15 μm vs 26 ± 24 μm, p = 0.005), reduced lipid arc (-29 ± 12° vs -18 ± 14°, p = 0.028), higher % decrease in total lipid arc (-35 ± 13% vs -19 ± 18%, p = 0.01), and lower major adverse cardiovascular event incidence (log-rank p = 0.023, hazard ratio 4.72 [1.08 to 20.63]) and revascularization rate (adjusted hazard ratio 6.77 [1.08 to 42.52]) than the non-SGLT2i group. In conclusion, SGLT2is can improve the markers of plaque stability and may improve the prognosis in patients with type 2 diabetes mellitus.

The value of Lp(a) and TG/HDLC in peripheral blood to assess the stability of carotid plaque in patients with ischemic stroke.

The objective of this study was to investigate the relationship between lipoprotein (a) (Lp(a)), triglyceride/high-density lipoprotein cholesterol (TG/HDL-C), and the stability of carotid atherosclerotic plaque in patients with acute ischemic stroke. A total of 142 patients with acute ischemic stroke were selected and divided into group A (59 cases of stable plaque formation) and group B (83 cases of unstable plaque formation) according to the characteristics of carotid artery plaque formation detected by carotid color Doppler ultrasound. The serum Lp(a), lipid metabolism indexes, peripheral blood routine indexes, and related serum inflammatory factors indexes were compared between the two groups. Receiver operating characteristic curve and multivariate logistic regression model were used to analyze the relationship between each index and the formation of carotid unstable plaque. There were no significant differences in serum total cholesterol (TC), HDL-C, and low-density lipoprotein cholesterol (LDL-C) between groups A and B (p > .05). The values of Lp(a), TG, and TG/HDL-C in group B were higher than those in group A, and the differences were statistically significant (p < .05). There were no significant differences in serum TC, HDL-C, and LDL-C between groups A and B (p > .05). The values of Lp(a), TG, and TG/HDL-C in group B were higher than those in group A, and the differences were statistically significant (p < .05). The values of HBA1C, Lp-PLA2, CRP, CysC, Hcy, TNF-α, neutrophils, and NLR in group B were higher than those in group A, and the differences were statistically significant (p < .05). There was no significant difference in FPG, systolic blood pressure, diastolic blood pressure, Hb, white blood cells, platelets, and lymphocytes between groups A and B (p > .05). The results of logistic regression model showed that the increase of Lp(a), TG/HDL-C, HBA1C, Lp-PLA2, CRP, CysC, Hcy, and NLR could increase the risk of carotid artery unstable plaque in patients with ischemic stroke (p < .05). Lp(a) and TG/HDL-C have certain value in evaluating the stability of carotid atherosclerotic plaque in patients with acute ischemic stroke, and the increased levels of LP (a) and TG/HDL-C will significantly increase the risk of carotid unstable plaque in patients.

Abstract 10227: High-Sensitive Magnetic Particle Imaging of Intraplaque Hemorrhage for Identification of Unstable Atherosclerotic Plaques

Introduction: Intraplaque hemorrhage (IPH), which is believed to arise from immature neovessels, drives atherosclerosis progression and is an imaging predictor of stroke and myocardial infarction. However, detection of IPH using magnetic resonance imaging (MRI) might be limited due to false signals from varied plaque components. Magnetic particle imaging (MPI) is a novel tomographic method that directly images the magnetization of ferromagnetic particles. Aims: To test whether MPI can image IPH for detecting unstable plaques and exploring the mechanism of IPH. Methods: The tandem stenosis (TS) mouse model was used to establish unstable plaques with IPH. The intervention agent used for reducing IPH was 4-ABAH. TS ApoE -/- mice and human carotid endarterectomy samples were scanned with MPI and computed tomography. IPH was confirmed by fat-suppressed T1-weighted MRI and Prussian blue staining. Plaque specimens were analyzed histologically. Results: Human carotid samples exhibited endogenous MPI signals, which were related to IPH. Hemosiderin was likely the source of MPI signals. Seven weeks post-TS, unstable plaques in the right carotid artery showed endogenous MPI signals, which were three-fold greater compared with stable plaques in the brachiocephalic artery or normal arterial wall (P &lt; 0.05). From the temporal points, MPI signals in unstable plaques increased from 3.05 ± 1.45 (4 weeks) to 7.29 ± 4.47 (7 weeks) and reduced to 2.59 ± 0.84 (11 weeks) (P &lt; 0.05), while intraplaque neovessel densities showed no difference. Compared with 4 or 7 weeks post-TS, intraplaque neovessels at 11 weeks revealed a more mature phenotype indicated by increased neovessel lumen areas and VE-cadherin (endothelial junction marker) expressions (P &lt; 0.05). Administered 4-ABAH attenuated MPI signals in unstable plaques (9.38 ± 6.75 vs. 3.11 ± 1.25, P &lt; 0.05) and downregulated vWF (endothelial damage marker) expressions (P &lt; 0.05) without affecting neovessel densities or lumen areas. Conclusions: MPI allows ex vivo IPH imaging in human carotid tissues, in vivo IPH monitoring and unstable plaque detection in ApoE -/- mice. MPI-detected IPH is likely associated with endothelial barrier function. As a result, MPI is a promising method for detecting unstable plaques in patients.

The risk of carotid plaque instability in patients with metabolic syndrome is higher in women with hypertriglyceridemia

BackgroundMetabolic syndrome certainly favors growth of carotid plaque; however, it is uncertain if it determines plaque destabilization. Furthermore, it is likely that only some components of metabolic syndrome are associated with increased risk of plaque destabilization. Therefore, we evaluated the effect of different elements of metabolic syndrome, individually and in association, on carotid plaques destabilization.MethodsA total of 186 carotid endarterectomies from symptomatic and asymptomatic patients were histologically analysed and correlated with major cardiovascular risk factors.ResultsMetabolic syndrome, regardless of the cluster of its components, is not associated with a significant increase in risk of plaque destabilization, rather with the presence of stable plaques. The incidence of unstable plaques in patients with metabolic syndrome is quite low (43.9 %), when compared with that seen in the presence of some risk factors, but significantly increases in the subgroup of female patients with hypertriglyceridemia, showing an odds ratio of 3.01 (95% CI, 0.25–36.30).ConclusionsOur data may help to identify patients with real increased risk of acute cerebrovascular diseases thus supporting the hypothesis that the control of hypertriglyceridemia should be a key point on prevention of carotid atherosclerotic plaque destabilization, especially in post-menopausal female patients.

Neutrophil Gelatinase Associated Lipocalin (NGAL) for Identification of Unstable Plaques in Patients with Asymptomatic Carotid Stenosis

Neutrophil Gelatinase Associated Lipocalin (NGAL) for Identification of Unstable Plaques in Patients with Asymptomatic Carotid Stenosis

Neutrophil Gelatinase Associated Lipocalin (NGAL) for Identification of Unstable Plaques in Patients with Asymptomatic Carotid Stenosis

Neutrophil gelatinase associated lipocalin (NGAL) and matrix metalloproteinase (MMP)-9/NGAL complex were investigated in asymptomatic patients with carotid artery stenosis including gender specific differences aiming at vulnerable plaques prone to embolisation. Serum NGAL and MMP-9/NGAL levels were analysed in 83 patients with asymptomatic carotid artery stenosis. Pre-operative ultrasound and post-endarterectomy histology of carotid atherosclerotic lesions were evaluated. Patients with vulnerable plaques, as determined by ultrasound (plaques with decreased echogenicity) and histological analysis (type VI according to the classification of the American Heart Association), displayed the highest levels of NGAL and MMP-9/NGAL complex (p=.0003 and p=.0078, respectively). Grade VI plaques were primarily detected in patients with "soft" plaques (12 type VI plaques in 25 patients), but also in patients with mixed (four of 19) and calcified (three of 39) plaques according to ultrasound. Higher grade carotid artery stenosis (≥90%) was not associated with elevated NGAL levels. The receiver operating characteristic curve analysis detecting grade VI lesions yields an area under the curve (AUC)=0.85, with respect to soft plaque on ultrasound the AUC=0.86. There were no gender specific differences in levels of NGAL 80.9 (37.7) ng/mL in women vs. 76.7 (36.3) ng/mL in men, p=.607) nor of MMP-9/NGAL 33.0 (18.2-55.5) ng/mL in women vs. 36.7 (20.2-54.0) ng/mL in men, p=.969. Likewise, there were no gender associated differences in vulnerable plaque characteristics: either for grade VI plaques (17.9% vs. 27.3%, p=.582) or for the presence of soft plaques as evaluated by ultrasound (35.9% vs. 25%, p=.503). Circulating NGAL and MMP-9/NGAL are significantly increased in asymptomatic patients with vulnerable carotid atherosclerotic plaques independent of gender. Accordingly, serum NGAL may be proposed as a valuable biomarker for the detection of unstable carotid plaques in asymptomatic patients, who can then be selected for early carotid endarterectomy or stenting.

The diagnosis of coronary plaque stability by multi-slice computed tomography coronary angiography.

Coronary computed tomographic angiography is a robust non-invasive method to assess coronary artery disease (CAD) and analyze coronary plaque stability, especially for the non-calcified plaques. The aim of this study was to investigate the differential characteristics between the unstable coronary plaques and the stable coronary plaques using multi-slice computed tomography (MSCT). Sixty patients with coronary heart disease (37 unstable plaques and 31 stable plaques) were included. The napkin ring thickness, napkin-ring sign, plaque CT attenuation and degree of lumen stenosis were retrospectively analyzed. The diagnostic performances of MSCT were determined to predict the unstable plaques. The difference was statistically significant if P<0.05. The napkin ring thickness of the unstable plaques was thinner than that of the stable plaques (P<0.05). The napkin-ring sign was more frequently observed in the unstable group (89.2%) than the stable group (22.6%, P<0.05). The average CT value of the unstable plaques (26.8±17.8 HU) was lower than that of the stable plaques (68.5±25.5 HU, P<0.05). The unstable plaques had more severe lumen stenosis or occlusion (70.3%) than the stable plaques (41.9%, P<0.05). The measurable napkin ring thickness of the plaques with a cutoff value of 0.8 mm and an accuracy of 89.5% was one independent factor to predict unstable plaques. The optimal combined threshold of the napkin-ring sign and/or the plaque CT value of 53 HU with an accuracy of 80.9% was to predict unstable plaques. The optimal combined threshold of the napkin-ring sign and/or the plaque CT value ≤53 HU may be a good indicator to predict the unstable plaques in patients with CAD. The subgroup of measurable napkin ring thickness of the non-calcified plaques may also be an independent factor to predict the unstable plaques in patients with CAD.

Mast cells are increased in the media of coronary lesions in patients with myocardial infarction and may favor atherosclerotic plaque instability

ObjectivesMast cells (MCs) may play an important role in plaque destabilization and atherosclerotic coronary complications. Here, we have studied the presence of MCs in the intima and media of unstable and stable coronary lesions at different time points after myocardial infarction (MI). MethodsCoronary arteries were obtained at autopsy from patients with acute MI (up to 5 days old; n=27) and with chronic MI (5–14 days old; n=18), as well as sections from controls without cardiac disease (n=10). Herein, tryptase-positive MCs were quantified in the intima and media of both unstable and stable atherosclerotic plaques in infarct-related and non-infarct-related coronary arteries. ResultsIn the media of both acute and chronic MI patients, the number of MCs was significantly higher than in controls. This was also found when evaluating unstable and stable plaques separately. In patients with chronic MI, the number of MCs in unstable lesions was significantly higher than in stable lesions. This coincided with a significant increase in the relative number of unstable plaques in patients with chronic MI compared with control and acute MI. No differences in MC density were found between infarct-related and non-infarct-related coronary arteries in patients with MI. ConclusionThe presence of MCs in the media of both stable and unstable atherosclerotic coronary lesions after MI suggests that MCs may be involved in the onset of MI and, on the other hand, that MI triggers intra-plaque infiltration of MCs especially in unstable plaques, possibly increasing the risk of re-infarction.

Circulating Microparticles and Coronary Plaque Components Assessed by Virtual Histology Intravascular Ultrasound of the Target Lesion in Patients with Stable Angina.

High levels of microparticles (MPs) circulate in the blood of patients with atherosclerotic diseases where they can serve as potential biomarkers of vascular injury and cardiovascular outcome. We used virtual histology intravascular ultrasound (VH-IVUS) to evaluate the relationship between the levels of circulating MPs and the coronary plaque composition in patients with stable angina. We included 35 patients with stable angina (22 men, age 64 ± 9 years) and a de novo target lesion. Preintervention gray-scale and VH-IVUS analysis was performed across the target lesion. Volumetric analysis was performed over a 10-mm-long segment centered at the minimum luminal site. Blood samples were obtained from the femoral artery before coronary angioplasty. MPs were measured using a solid-phase capture assay from a commercial kit. We divided participants into either a low MPs group or high MPs group based on the median value of MPs. There was no significant difference in baseline characteristics between the groups. The plaque burden and remodeling index were similar between the groups. The presence of VH-IVUS-derived thin-cap fibroatheroma was not different between the groups. The percentage of the necrotic core (NC) was significantly higher in the high MPs group than in the low MPs group, both in planar (17.0 ± 8.8% vs. 24.1 ± 6.9%, p = 0.012) and volumetric analyses (17.0 ± 4.8% vs. 22.1 ± 4.3%, p = 0.002). Circulating MPs were positively correlated with the percentage of the NC area at the minimal luminal site (r = 0.491, p = 0.003) and the percentage of the NC volume (r = 0.496, p = 0.002). Elevated levels of circulating MPs were associated with the amount of NC in the target lesion in those with stable angina, suggesting a potential role of circulating MPs as a biomarker for detecting unstable plaque in patients with stable angina.

Feasibility of diagnosing unstable plaque in patients with acute coronary syndrome using iMap-IVUS.

To compare the plaque composition between stable and unstable plaques, characterize unstable plaque by using iMap-intravascular ultrasound (IVUS), and quantify the diagnostic criteria for unstable plaque. Thirty-three acute coronary syndrome (ACS) patients who had undergone coronary angiography and IVUS from February 19, 2014 to December 19, 2014 at Peking University People's Hospital were enrolled in the study. Baseline data were collected. The patients were divided into two groups according to their gray-scale IVUS imaging, stable plaque and unstable plaque. A difference-in-difference evaluation was performed using the baseline data and off-line iMap imaging results between the two groups. A receiver operating characteristic (ROC) curve was constructed to obtain the optimal cut-off value to diagnose unstable plaque. Percentages of fibrotic and necrotic tissues, absolute values of lipidic, necrotic, and calcified tissues, and plaque burden were independent predictors for unstable plaque. Absolute necrotic area was the best predictor and exhibited the highest diagnostic value for plaque vulnerability (area under the curve (AUC)=0.806, P=0.000, 95% CI (0.718, 0.894)). The cut-off score for predicting unstable plaque was 4.0 mm(2). This study attempted to propose a cut-off value based on absolute necrotic area using iMap-IVUS to predict plaque vulnerability in patients with ACS. This score might provide a valuable reference for diagnosing unstable plaque.

Increased FGF23 serum level is associated with unstable carotid plaque in type 2 diabetic subjects with internal carotid stenosis.

BackgroundThe object of this study was to investigate the potential role of FGF23 on plaque stability in type 2 diabetic patients with internal carotid artery stenosis.MethodsIn this retrospective observational study, we analyzed FGF23 serum level in 361 type 2 diabetic patients with internal carotid artery stenosis undergoing carotid endarterectomy and in 598 diabetic controls without carotid atherosclerosis.ResultsWe found that FGF23 median serum levels was significantly higher in patients than in diabetic controls [67.7 (59.5–77.8) pg/mL and 43.89 (37.5–50.4), P < 0.001] and was significantly and independently associated with unstable plaque in patients with internal carotid artery stenosis [OR, 5,71 (95 % CI, 2.09–15.29].ConclusionsWe have found, for the first time, that FGF23 could be associated with unstable plaque in type 2 diabetic patients with internal carotid artery stenosis.

Plasmatic Level of Leukocyte-Derived Microparticles Is Associated With Unstable Plaque in Asymptomatic Patients With High-Grade Carotid Stenosis

This study sought to analyze whether the plasmatic level of leukocyte-derived microparticles (LMP) is associated with unstable plaques in patients with high-grade carotid stenosis. Preventive carotid surgery in asymptomatic patients is currently debated given the improvement of medical therapy. Therefore, noninvasive biomarkers that can predict plaque instability are needed. The LMPs, originating from activated or apoptotic leukocytes, are the major microparticle (MP) subset in human carotid plaque extracts. Forty-two patients with >70% carotid stenosis were enrolled. Using a new standardized high-sensitivity flow cytometry assay, LMPs were measured before thromboendarterectomy. The removed plaques were characterized as stable or unstable using histological analysis according to the American Heart Association criteria. The LMP levels were analyzed according to the plaque morphology. The median LMP levels were significantly higher in patients with unstable plaque (n = 28; CD11bCD66b+ MP/μl 240 [25th to 75th percentile: 147 to 394], and CD15+ MP/μl 147 [60 to 335]) compared to patients with stable plaque (16 [0 to 234] and 55 [36 to 157]; p < 0.001 and p < 0.01, respectively). The increase in LMP levels was also significant when considering only the group of asymptomatic patients with unstable plaque (n = 10; CD11bCD66b+ MP/μl 199 [153 to 410] and CD15+ MP/μl 78 [56 to 258] compared with patients with stable plaque (n = 14; 20 [0 to 251] and 55 [34 to 102]; p < 0.05 and p < 0.05, respectively). After logistic regression, the neurologic symptoms (odds ratio: 48.7, 95% confidence interval: 3.0 to 788, p < 0.01) and the level of CD11bCD66b+ MPs (odds ratio: 24.4, 95% confidence interval: 2.4 to 245, p < 0.01) independently predicted plaque instability. LMP constitute a promising biomarker associated with plaque vulnerability in patients with high-grade carotid stenosis. These data provide clues for identifying asymptomatic subjects that are most at risk of neurologic events.

Dose Dependent Changes of Lipid Profiles, IL-6 and CRP in Unstable Angina Patients after Simvastatin Therapy

Background and Objectives:The beneficial effects of statins in preventing cardiovascular events may depend, in part, on their anti-inflammatory action. We previously reported that low dose statin therapy has cholesterol lowering effects, but no effect on inflammation, and proposed that a sufficient dose of therapy might be needed to achieve anti-inflammatory action. The aims of this study were to confirm the suggestions made in our previous study. Subjects and Methods:Fifteen unstable angina patients who were enrolled in our previous study were evaluated. The usual dose (20 mg) of simvastatin was administrated for 26 weeks, blood samples collected following the administration and tested for their lipid profiles and inflammatory markers (IL-6, CRP). The changes in the lipid profiles and inflammatory markers, from baseline levels, to the usual and low doses of statin therapy were evaluated. Results:The changes in the IL-6 and hsCRP levels after the usual dose simvastatin therapy compared with the baseline levels were -72.8 and -59.6% (p<0.05), respectively. The changes in the IL-6 and hsCRP levels after the usual dose simvastatin therapy compared with a 5 mg dose were -77.2 and -47.1% (p<0.05), respectively. There was statistically significant correlation between the change in the levels of IL-6 and hsCRP during statin therapy. Conclusion:Our data confirmed the preliminary result of Chung et al, which suggested the usual dose of simvastatin is required to inhibit the inflammation of unstable plaque in patients with unstable angina associated with hypercholesterolemia. (Korean Circulation J 2003;33 (8):663-670)

Detection of Unstable Plaques in Patients with Carotid Stenosis Using B-Mode Ultrasonography

Distal embolism is a detrimental complication of stent placement for the carotid artery stenosis. To evaluate usefulness of B-mode ultrasonography (US) for the detection of unstable plaques in patients with carotid artery stenosis, we examined US in 46 arteries of 35 patients with carotid stenosis of > 30%. The echogenicity of 46 carotid plaques was hyperechoic in 20 plaques, hypoechoic in 15, and mixed-echoic in 11. The echogenicity of carotid plaques was correlated with severity of carotid stenosis, ipsilateral stroke or TIA, heart attack, and risk factors of systemic atherosclerosis. Hypoechoic plaques were associated with severe carotid stenosis and ipsilateral ischemic event. Mixed-echoic plaques had a high incidence of past history of heart attack. Hyperechoic plaques were less likely to associate with risk factors of systemic atherosclerosis. We developed a new method of echodensity analysis. Using a computer software, echodensity values of seven plaque components were determined by comparing US findings and pathology of surgical specimens. The echodensity value was defined as a relative value to the arterial lumen. The calcified part of plaques had the highest echodensity of 6.24 +/- 0.86 (mean +/- 2 S.D.); fibrosis or hyarynoid degeneration of 2.05 +/- 0.40, foamy histiocytes of 1.47 +/- 0.05, necrosis of 1.32 +/- 0.16, cholestelin clefts of 1.28 +/- 0.13, intraplaque hemorrhage of 1.02 +/- 0.09, and intraluminal thrombus of 1.27 +/- 0.07. Constructed from the echodensity value, an echo-densitometry color mapping of the carotid plaque illustrated the exact location and extent of plaque component. B-mode US of carotid plaques represents clinical characteristics relating distal embolism and systemic atherosclerosis. A new method of echodensity analysis and echo-densitometry color mapping of the carotid plaque is useful to detect unstable plaques in patients with carotid stenosis.