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Objective:To evaluate the effect of statins combined with PCSK9 inhibitors on coronary artery atherosclerotic plaque, as well as to verify the lipid-lowering effect of the combined therapy.Methods:A computerized search of PubMed, Embase, Web of Science, Cochrane Library, Wanfang, and CNKI databases was conducted to retrieve published literature from inception to December 20, 2022. The English search terms utilized included "PCSK9 inhibitors," "Alirocumab," "Evolocumab," "plaque," "IVUS," and "OCT." The corresponding Chinese search terms were "PCSK9 inhibitors," "plateau," "intravascular ultrasound," and "optical coherence tomography." The literature that examined the effect of statins alone or in combination with PCSK9 inhibitors on coronary atherosclerotic plaques using intravascular ultrasound or optical coherence tomography was identified. The collected data were subsequently processed using Review Manager (Revman) version 5.4.Results:In the final analysis, nine studies involving 1912 patients were included. The analysis results revealed that compared with statins alone, statins combined with PCSK9 inhibitors significantly reduced the percentage of atherosclerotic volume ( MD: -2.08 mm 3, 95% CI: -2.94 to -1.23 mm 3, P < 0.001), accelerated the regression of atherosclerotic volume ( MD: -1.13 mm 3, 95% CI: -1.49 to -0.77 mm 3, P < 0.001), slightly, but not significantly, reduced the overall atherosclerotic volume ( MD: -6.42 mm 3, 95% CI: -14.34-1.51 mm 3, P = 0.110). Nevertheless, the combined therapy contributed to a significant reduction in atherosclerotic volume ( MD: -5.16 mm 3, 95% CI: -7.09 to -3.23 mm 3, P < 0.001) and significantly increased the fiber cap thickness of thin cap plaques ( MD: 8.46 μm, 95% CI: 5.13-11.79 μm, P < 0.001). Additionally, this combined therapy significantly lowered blood lipid levels. Conclusion:The combination of statins and PCSK9 inhibitors can significantly improve the characteristics and phenotype of atherosclerotic plaques and significantly reduce blood lipid levels. For patients with high cardiovascular risk, it is recommended to initiate treatment with statins combined with PCSK9 inhibitors as soon as possible and maintain it for a long time to ensure more benefits.
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Objective:To construct 68Ga-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-CD44 as a novel atherosclerosis tracer targeting hyaluronic acid (HA), and evaluate its biological property and molecular imaging features. Methods:Low molecular weight (LMW) recombinant human CD44 protein was selected, and the C-terminal of the protein was modified by sulfonation and coupled to the bifunctional ligand NOTA to synthesize a novel molecular probe 68Ga-NOTA-CD44 targeting HA. The biological properties of the probe, such as labeling rate and in vitro stability, were studied. Three atherosclerotic plaque model mice and three normal C57BL/6 mice were studied by 68Ga-NOTA-CD44 microPET/CT imaging and pathological examination. Results:68Ga-NOTA-CD44 tracer was synthesized and purified with the radiochemical purity above 99%, and the specific activity was up to 62.22 MBq/nmol. lts stability was good in PBS, and the radiochemical purity was over 90% after incubation for 3 h. After intravenous injection, the probe was metabolized mainly by the kidneys, and its metabolic level decreased successively in the liver, lungs and blood. MicroPET/CT imaging results of atherosclerotic model mice suggested that the uptake in the plaque of abdominal aorta was higher at 60 min after injection, with SUV max and target/background ratio (TBR) max of 1.14±0.02 and 4.95±0.93, and the probe had certain atherosclerotic plaque eroded targeting, which was consistent with the pathological result. Conclusions:As a novel probe, 68Ga-NOTA-CD44 is simple to prepare and has a high labeling rate. It has good physicochemical properties and in vivo biological properties, and can display atherosclerotic eroded plaques sensitively. 68Ga-NOTA-CD44 has a promising prospect to be a new molecular probe for early noninvasive recognition of atherosclerotic eroded plaques.
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Isolated pontine infarction (IPI) is the main type of acute brainstem infarction. Due to the application of high-resolution MRI, the research on the etiology of IPI has gradually increased in recent years. This article reviews the latest research progress on the characteristics of basilar artery plaques and disease progression mechanisms of IPI, aiming to provide reference for the etiology research of IPI.
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Carotid atherosclerosis is closely associated with ischemic stroke. Research shows that the rupture of vulnerable carotid plaque is an important reason for carotid atherosclerosis leading to thromboembolic events. Therefore, early identification of vulnerable carotid plaques is of great significance for the diagnosis, treatment, and prevention of ischemic stroke. This article reviews the pathophysiological features, imaging evaluation of carotid plaque and its relationship with ischemic stroke.
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Intracranial atherosclerotic stenosis (ICAS) is the main cause of patients with stroke in China. How to accurately detect and identify vulnerable plaques through imaging examinations, and strengthen the prediction and prevention of ischemic stroke in patients with ICAS, is a key clinical problem that needs to be solved, and is also a current challenge. With the application of magnetic resonance vascular wall imaging in ICAS, imaging examinations provide useful information on the vascular structure and plaque stability at the stenosis in addition to the degree of stenosis. It has improved the ability to evaluate ICAS and promoted its development towards more accurate diagnosis and treatment.
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Objective:To investigate the predictive value of systemic inflammatory response index (SIRI) for early neurological deterioration (END) and clinical outcome in patients with branch atherosclerotic disease (BAD).Methods:Consecutive patients with BAD admitted to the Department of Neurology, Jiangyin People’s Hospital Affiliated to Southeast University from September 2021 to September 2022 were retrospectively included. The clinical data were collected and SIRI was calculated. The calculation method of SIRI was neutrophil count × monocyte count/lymphocyte count. END was defined as an increase of ≥2 in the total score of the National Institutes of Health Stroke Scale (NIHSS) or an increase of ≥1 in the motor function score within 1 week of onset. The modified Rankin Scale was used for outcome evaluation at 3 months after onset, with a score >2 were defined as poor outcome. Multivariate logistic regression analysis was used to determine the independent correlation between SIRI and END, as well as poor outcome. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of SIRI for poor outcome. Results:A total of 125 patients with BAD were included, of which 62 (49.6%) had END and 32 (25.6%) had poor outcome. The multivariate logistic regression analysis showed that intravenous thrombolysis (odds ratio [ OR] 1.083, 95% confidence interval [ CI] 1.082-1.240; P=0.043) and high SIRI ( OR 1.465, 95% CI 1.150-3.676; P=0.028) were independent risk factors for END in patients with BAD; END ( OR 1.130, 95% CI 1.032-1.384; P=0.006), high baseline NIHSS score ( OR 1.571, 95% CI 1.184-2.101; P=0.003) and high SIRI ( OR 2.062, 95% CI 1.152-3.672; P=0.01) were independent risk factors for poor outcome in patients with BAD. ROC curve analysis showed that the area under the curves for SIRI, baseline NIHSS score, and the both combined prediction of poor outcome were 0.66 (95% CI 0.54-0.78), 0.70 (95% CI 0.58-0.81), and 0.83 (95% CI 0.74-0.93), respectively. Conclusions:High SIRI is an independent risk factor for END and poor outcome in patients with BAD. The SIRI and baseline NIHSS scores have certain predictive value for poor outcome in patients with BAD, and their combined diagnostic value is higher.
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The intestinal microbiota participates in maintaining the homeostasis of the intestinal environment, and the imbalance caused by changes in its composition or distribution and activity is called intestinal microbiota imbalance. Carotid atherosclerosis, especially vulnerable carotid plaques, will increase the risk of ischemic stroke. Researches have shown that intestinal microbiota can participate in the occurrence and development of carotid artery plaques through its metabolites as signaling molecules, and targeted drugs that improve intestinal microbiota imbalance are expected to become a new treatment modality for vulnerable carotid artery plaques.
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Objective:To investigate the correlation between serum inflammatory markers and carotid plaque and its stability in patients with acute ischemic stroke (AIS).Methods:Patients with AIS admitted to Liaocheng Third People’s Hospital from June 2021 to April 2022 were prospectively enrolled. The demographic and relevant clinical data were collected. Color Doppler ultrasound was used to detect carotid artery plaques. The patients were divided into unstable plaque group, stable plaque group and non-plaque group according to plaque characteristics. The levels of serum hypersensitive C-reactive protein (hs-CRP), serum amyloid A (SAA) and interleukin (IL) -6 were detected and compared. Multivariate logistic regression analysis was used to determine the independent risk factors for carotid plaque and its stability. Results:A total of 201 patients with AIS were enrolled, including 87 patients (43.30%) in the non-plaque group, 57 (28.35%) in the stable plaque group, and 57 (28.35%) in the unstable plaque group. The proportion of patients with hypertension and previous stroke history, and hs-CRP, SAA and IL-6 levels in the unstable plaque group was significantly higher than those in the stable plaque group and the non-plaque group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for other confounding factors, the increased IL-6 level (odds ratio [ OR] 1.174, 95% confidence interval [ CI] 1.049-1.314; P=0.005) was an independent risk factor for the existence of stable plaques, while the previous stroke history ( OR 3.172, 95% CI 1.123-8.957; P=0.029) and the increased IL-6 level ( OR 1.367, 95% CI 1.107-1.687; P=0.004) were the independent risk factors for the existence of unstable plaques. Conclusion:The serum IL-6 level in patients with AIS increase significantly, which is closely associated with the formation and stability of carotid plaques.
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Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays a central role in the regulation of calcium, phosphorus and active vitamin D levels. Recent studies have shown that high FGF23 is associated with cardiocerebrovascular diseases. This article reviews the correlation between FGF23 and cerebrovascular diseases.
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Aim: To evaluate the prevalence of soft tissue calcifications in orofacial region and their panoramic radiographic characteristics using digital panoramic radiographs among patients reporting to a tertiary dental hospital. Methods: 1,578 digital panoramic radiographs were retrieved from the archives and scrutinized for the presence of calcifications. Soft tissue calcifications were recorded according to age, gender, site (left or right). Data were analysed using Chi-square and Fisher's exact test using SPSS software and a p < 0.05 was considered statistically significant. Results: Among the total number of radiographs, calcified carotid artery (34.3%), calcified stylohyoid ligament (21%), tonsillolith (10.3%), phlebolith (17.6%), antrolith (6.3%), sialolith (5.9%), rhinolith (2.5%) and calcified lymph nodes (1.9%) were identified. The most commonly observed calcifications were calcification of carotid artery and stylohyoid ligament and the least commonly observed calcifications were rhinolith and calcified lymph node. A statistically significant association of the presence of calcifications of carotid artery and stylohyoid ligament on the left and right side was observed in females and tonsillolith on the right side in males (p-value < 0.05). Considering the gender and age group, the occurrence of antrolith among males and rhinolith among females of young-adult population, tonsillolith among the males, calcified carotid artery and stylohyoid ligament among the females of middle-aged population was found to be significant. Conclusion: Soft tissue calcifications are often encountered in dental panoramic radiographs. Our study revealed that the soft tissue calcifications in orofacial region were more common in women and were found to be increased above 40 years of age
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Humans , Male , Female , Prune Belly Syndrome , Calcinosis/epidemiology , Diagnostic Imaging , Radiography, Panoramic , Plaque, AtheroscleroticABSTRACT
Resumo Fundamento A formação de células espumosas ocorre devido ao aumento em lipoproteína plasmática de baixa densidade (LDL) e desregulação da inflamação, sendo importante para o desenvolvimento da aterosclerose. Objetivo Avaliar o perfil do fator de necrose tumoral alfa (TNF-α) e da interleucina-6 (IL-6) no método de formação da célula espumosa existente, otimizando esse protocolo. Métodos A LDL foi isolada, oxidada e marcada com sonda de isotiocianato de fluoresceína (FITC). As células espumosas foram geradas de célula derivada de monócitos humanos THP-1 e incubadas na ausência (controle) ou presença de FITC-ox-LDL (10, 50, 100, 150 ou 200 μg/mL), por 12, 24, 48 ou 72 horas. A FITC-ox-LDL na célula foi quantificada por microscopia. O ensaio de imunoabsorção enzimática foi avaliado para quantificar a IL-6 e o TNF-α, com um p <0,05 considerado significativo. Resultados Todas as concentrações de FITC-ox-LDL testadas apresentaram fluorescência mais alta em comparação com o controle, demonstrando maior acúmulo de lipoproteínas nas células. Quanto mais alta a concentração de FITC-ox-LDL, maior a produção de TNF-α e IL-6. A produção de IL-6 pelas células espumosas foi detectada até o valor de 150 µg/mL da LDL máxima de estímulo. Concentrações acima de 50 μg/mL de LDL estimularam maior liberação de TNF-α comparado ao controle. Conclusões Nosso modelo contribui para o entendimento da liberação de IL-6 e TNF-α em resposta a várias concentrações de ox-LDL usando o método otimizado para a formação de células espumosas.
Abstract Background The formation of foam cells occurs due to the increase in low-density plasma lipoprotein (LDL) and dysregulation of inflammation, which is important for the development of atherosclerosis. Objective To evaluate the profile of tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) in the existing foam cell formation method, optimizing this protocol. Methods The LDL was isolated, oxidized, and labeled with a Fluorescein isothiocyanate (FITC) probe. Foam cells were generated from THP-1 human monocyte-derived cells and incubated in the absence (control) or presence of FITC-ox-LDL (10, 50, 100, 150, or 200 μg/mL), for 12, 24, 48, or 72 hours. The accumulated FITC-ox-LDL in the cell was quantified by microscopy. The enzyme-linked immunosorbent assay was evaluated to quantify the IL-6 and TNF-α, with p < 0.05 considered significant. Results All the FITC-ox-LDL concentrations tested showed a higher fluorescence when compared to the control, showing a greater accumulation of lipoprotein in cells. The higher the concentration of FITC-ox-LDL, the greater the production of TNF-α and IL-6. The production of IL-6 by foam cells was detected up to the value of 150 µg/mL of the maximum stimulus for LDL. Concentrations above 50 μg/mL LDL stimulated greater release of TNF-α compared to control. Conclusions Our model contributes to the understanding of the release of IL-6 and TNF-α in response to different concentrations of ox-LDL, using an optimized method for the formation of foam cells.
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Objective:To investigate the evaluation value of optical coherence tomography (OCT) for carotid atherosclerotic plaques.Methods:Patients with carotid atherosclerotic stenosis underwent digital subtraction angiography (DSA) and OCT in the Affiliated Hospital of Jining Medical College from January 2020 to January 2022 were retrospectively enrolled. The demographics, baseline clinical data, DSA and OCT imaging data of the symptomatic group and the asymptomatic group were compared. Multivariate logistic regression analysis was used to determine the independent risk factors for symptomatic carotid atherosclerotic stenosis. Results:A total of 39 patients were enrollded, including 21 in the symptomatic group and 18 in the asymptomatic group. The detection rate of fibrous plaque in the symptomatic group was significantly lower than that in the asymptomatic group (38.1% vs. 77.78%; P=0.023), while the detection rate of plaque rupture (38.1% vs. 5.56%; P=0.023) and macrophage infiltration (42.86% vs. 11.11%; P=0.037) was significantly higher than that in the asymptomatic group. Multivariate logistic regression analysis showed that plaque rupture (odds ratio 6.982, 95% confidence interval 1.068-45.660; P=0.043) and macrophage infiltration (odds ratio 6.480, 95% confidence interval 1.009-41.625; P=0.049) were significantly independently associated with the symptomatic carotid atherosclerotic stenosis. Conclusions:OCT is of value in evaluating the plaque characteristics of carotid atherosclerotic stenosis. Plaque rupture and macrophage infiltration are the independent risk factors for symptomatic carotid atherosclerotic stenosis.
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Intracranial artery stenosis is the main cause of ischemic stroke in China. Because of the high recurrence rate of stroke in these patients, the selected patients may benefit from interventional therapy. Therefore, risk stratification and evaluation of intracranial artery stenosis are helpful to determine the clinical treatment plan. High resolution magnetic resonance imaging can clearly show the characteristics of intracranial vascular wall, which is helpful to comprehensively evaluate intracranial vessels. This article reviews the characteristics of vulnerable plaque of intracranial atherosclerosis, the pathogenesis of stroke and the clinical application of high-resolution magnetic resonance imaging in intracranial artery stenosis.
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Vulnerable plaque rupture is the leading cause of acute cardiovascular diseases. Macrophages are main inflammatory cells closely related to the rupture of vulnerable plaques. Early diagnosis of vulnerable plaque can reduce the mortality of acute cardiovascular diseases. With the development of molecular imaging, the possibility for early identification of vulnerable plaques may come true. This review summarizes the changes of molecular markers of macrophages in vulnerable plaques and the molecular probes that can target macrophages.
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Objective:To evaluate carotid plaque neovascularization and vessel stability using superb microvascular imaging.Methods:Seventy-two patients with carotid atherosclerotic plaques received treatment in The Seventh People's Hospital of Wenzhou from June 2018 to June 2020 and were included in this study. A total of 100 carotid plaques were surgically removed from these patients. These patients were subject to superb microvascular imaging and contrast-enhanced ultrasonography before carotid plaques were removed. Taking pathological results of carotid plaque as a gold standard, we investigated the efficacy of superb microvascular imaging versus contrast-enhanced ultrasonography in detecting carotid plaque neovascularization and vessel stability and evaluated the detection consistency of each imaging method with the gold standard. Results:The sensitivity, specificity, and accuracy of superb microvascular imaging in detecting carotid plaque neovascularization were 93.24%, 92.31%, and 93.00%, and they were 95.96%, 96.15%, and 96.00% for contrast-enhanced ultrasonography. The Kappa values of consistency of agreement on carotid plaque neovascularization identification were 0.825 and 0.923 for superb microvascular imaging and contrast-enhanced ultrasonography, respectively. The sensitivity, specificity, and accuracy of superb microvascular imaging in detecting vessel stability were 94.74%, 95.35%, and 95.00%, respectively and they were 96.49%, 97.67%, and 97.00%, respectively for contrast-enhanced ultrasonography. The Kappa values of consistency of agreement on vessel stability evaluation were 0.898 and 0.939 for superb microvascular imaging and contrast-enhanced ultrasonography, respectively.Conclusion:Superb microvascular imaging has equivalent efficacy in detecting carotid plaque neovascularization and vessel stability to contrast-enhanced ultrasonography. Superb microvascular imaging is non-invasive, provides ease in operation, and is worthy of clinical promotion.
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As a new technology for screening carotid plaques, three-dimensional ultrasound plays an important role in clinical and scientific research. Recent studies have shown that three-dimensional ultrasound combined with various new algorithms can effectively evaluate carotid plaque load and vulnerability. However, due to the high cost of volumetric probes and the large volume affecting the detection angle, three-dimensional ultrasound has not been widely used in China. This article reviews the advantages of three-dimensional ultrasound in evaluating vulnerable plaques and plaque load, in order to provide reference for clinical work in the future.
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Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of ischemic cerebrovascular disease. Compared with other causes such as extracranial diseases or cardiogenic embolism, symptomatic ICAS (sICAS) has a higher risk of stroke recurrence, often leading to the aggravation of neurological impairment and even death. More and more evidence shows that imaging features play an important role in predicting the risk of stroke recurrence and individualized secondary prevention in patients with sICAS. This article reviews the imaging features of ischemic stroke recurrence in patients with sICAS, which provides a basis for identifying sICAS patients with high risk of recurrent stroke and effective secondary prevention.