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Insulin resistance (IR) is linked to both the vulnerable plaque and the stroke risk. However, the precise extent of this correlation and its impact on stroke risk in carotid artery stenosis patients remain unclear. Therefore, this study aims to investigate the relationship between vulnerable plaque and IR and stroke risk and the mediating role of vulnerable plaque in patients with carotid artery stenosis. This study included 505 patients with carotid artery stenosis. IR was assessed using the triglyceride-glucose (TyG) index. The association of the TyG index and vulnerable plaque with stroke risk was investigated using the restricted cubic splines (RCS)and adjusted Logistic regression. Additionally, the mediation analysis was used to explore the mediating impact of the vulnerable plaque on the association between the TyG index and stroke risk. A total of 184 (36.4%) stroke events were recorded. The RCS curves revealed a positive linear association between TyG index and risk events among patients with carotid artery stenosis (P-value < 0.001 and P for nonlinear = 0.860). After fully adjusting for covariates, both the TyG index and vulnerable plaque emerged as significant predictors of stroke events. Mediation analysis indicated that the vulnerable plaque mediated 18.3%, 15.8%, 13.9%, and 11.6% of the correlation between the TyG index and stroke risk in different adjusted models, respectively. TyG index and vulnerable plaque are associated with a higher risk of stroke in patients with carotid artery stenosis. In addition, vulnerable plaques partially mediated the relationship between TyG index and stroke risk.

Cervical and transcranial Doppler (TCD) are widely used as non-invasive methods in the evaluation of acute ischemic stroke (AIS) patients. High-grade carotid artery stenosis induces haemodynamic changes such as collateral flow and a so-called post-stenotic flow pattern of the middle cerebral artery (MCA), which appears flattened, with a reduction of the velocity difference between systole and diastole. We studied the influence of carotid artery stenosis and other variables on the flow pattern in the MCA using the pulsatility index (PI), a quantitative TCD parameter reflecting the flow spectrum in a large of cohort AIS patients. We performed ultrasound examinations of 1825 AIS patients at the CHUV from October 2004 to December 2014. We extracted patient characteristics from the ASTRAL registry. Carotid stenosis severity was classified as < 50%, 50–70%, 70–90% and > 90%, or occlusion, according to Doppler velocity criteria. We first determined variables associated with stenosis grade. Then we performed a multivariate analysis after adjusting for baseline differences, using MCA PI as dependent variable. Carotid stenosis > 70% (− 0.07) and carotid stenosis > 90%, or occlusion (− 0.14) and left side (− 0.02) are associated with lower MCA PI values. Age (+0.006 PI units per decade), diabetes (+0.07), acute ischemic changes on initial CT (+0.03) and severe plaque morphology (+0.18) are associated with higher MCA PI values. We found a number of clinical and radiological conditions that significantly influence the PI of the MCA, including high-grade ipsilateral carotid stenosis in AIS patients. We provide for the first time a quantitative evaluation of the effect of these influencing factors from a large cohort of AIS patients.

The aorta is the ‘greatest artery’, through which oxygenated blood is delivered from the left ventricle to end organs with each cardiac cycle (200 million litres of blood transported in an average lifetime). The aorta can be affected by a wide spectrum of acute factors (such as cocaine use, weight lifting and trauma) and chronic acquired and/or genetic conditions (such as systemic arterial hypertension and phaeochromocytoma), which variously lead to increased aortic wall stress. The medial layer of the aorta can also be subject to abnormalities (such as Marfan syndrome, bicuspid aortic valve, inflammatory vasculitis, atherosclerosis and infections). Despite important advances in diagnostic and therapeutic interventions, data derived from registries and population-based studies highlight that the burden of aortic diseases remains high. Therefore, specific resources need to be allocated to design and implement preventive strategies (healthy lifestyles, modifications to cardiovascular risk factors, and educational and screening programmes) at individual and community levels. In this Review, we discuss the epidemiology, management and outcomes of the most common aortic diseases, namely, aortic aneurysms and acute aortic syndromes.In this Review, Bossone and Eagle discuss the epidemiology, management and outcomes of the most common aortic diseases: aortic aneurysms and acute aortic syndromes, including aortic dissection.

Herein, we aimed to identify blood biomarkers that compensate for the poor specificity of D-dimer in the diagnosis of deep vein thrombosis (DVT). S100A8 was identified by conducting protein microarray analysis of blood samples from patients with and without DVT. We used ELISA to detect S100A8, VCAM-1, and ICAM-1 expression levels in human blood and evaluated their correlations. Additionally, we employed human recombinant protein S100A8 to induce human umbilical vein endothelial cells and examined the role of the TLR4/MAPK/VCAM-1 and ICAM-1 signaling axes in the pathogenic mechanism of S100A8. Simultaneously, we constructed a rat model of thrombosis induced by inferior vena cava stenosis and detected levels of S100A8, VCAM-1, and ICAM-1 in the blood of DVT rats using ELISA. The associations of thrombus tissue, neutrophils, and CD68-positive cells with S100A8 and p38MAPK, TLR4, and VCAM-1 expression levels in vein walls were explored. The results revealed that blood S100A8 was significantly upregulated during the acute phase of DVT and activated p38MAPK expression by combining with TLR4 to enhance the expression and secretion of VCAM-1 and ICAM-1, thereby affecting the occurrence and development of DVT. Therefore, S100A8 could be a potential biomarker for early diagnosis and screening of DVT.

Vascular calcification is a complex biological process that is a hallmark of atherosclerosis. While macrocalcification confers plaque stability, microcalcification is a key feature of high-risk atheroma and is associated with increased morbidity and mortality. Positron emission tomography and X-ray computed tomography (PET/CT) imaging of atherosclerosis using 18 F-sodium fluoride ( 18 F-NaF) has the potential to identify pathologically high-risk nascent microcalcification. However, the precise molecular mechanism of 18 F-NaF vascular uptake is still unknown. Here we use electron microscopy, autoradiography, histology and preclinical and clinical PET/CT to analyse 18 F-NaF binding. We show that 18 F-NaF adsorbs to calcified deposits within plaque with high affinity and is selective and specific. 18 F-NaF PET/CT imaging can distinguish between areas of macro- and microcalcification. This is the only currently available clinical imaging platform that can non-invasively detect microcalcification in active unstable atherosclerosis. The use of 18 F-NaF may foster new approaches to developing treatments for vascular calcification. Atherosclerotic plaques with macrocalcification are stable, whereas microcalcification is a key feature of rupture-prone plaques. Here the authors show that 18 F-NaF PET/CT imaging can distinguish between macro- and microcalcification providing a potential, non-invasive imaging technique to identify patients with high-risk atheroma.

To investigate the change trends of plasma D-dimer during catheter-directed thrombolysis (CDT) in acute lower limb ischemia (ALI) patients and their clinical value. A retrospective review of patients with ALI who received CDT was carried out. The repeated measurements of plasma D-dimer were analyzed by generalized estimating equations (GEEs) and the change trends of D-dimer were analyzed by spline regression approach. A total of 150 patients were included. Among them, 3 days of CDT was ineffective in 41 cases, effective in 33 cases and markedly effective in 76 cases. The results of GEEs analysis showed that serum D-dimer changed significantly with time (time effect, P < 0.001). Serum D-dimer levels of patients with different treatment outcomes were different after treatment (group effect, P < 0.001), and serum D-dimer levels in these three groups showed different trends over time (group*time effect, P < 0.001). The different trends in serum D-dimer level with time after treatment in the three groups could be directly seen in the spline regression curve (P < 0.001). The plasma D-dimer changes regularly during CDT for ALI. We can predict the efficacy of CDT and guide adjustments of the therapeutic regimen according to the trend of D-dimer changes during thrombolysis.

The detection and characterization of coronary artery stenosis and atherosclerosis using imaging tools are key for clinical decision-making in patients with known or suspected coronary artery disease. In this regard, imaging-based quantification can be improved by choosing the most appropriate imaging modality for diagnosis, treatment and procedural planning. In this Consensus Statement, we provide clinical consensus recommendations on the optimal use of different imaging techniques in various patient populations and describe the advances in imaging technology. Clinical consensus recommendations on the appropriateness of each imaging technique for direct coronary artery visualization were derived through a three-step, real-time Delphi process that took place before, during and after the Second International Quantitative Cardiovascular Imaging Meeting in September 2022. According to the Delphi survey answers, CT is the method of choice to rule out obstructive stenosis in patients with an intermediate pre-test probability of coronary artery disease and enables quantitative assessment of coronary plaque with respect to dimensions, composition, location and related risk of future cardiovascular events, whereas MRI facilitates the visualization of coronary plaque and can be used in experienced centres as a radiation-free, second-line option for non-invasive coronary angiography. PET has the greatest potential for quantifying inflammation in coronary plaque but SPECT currently has a limited role in clinical coronary artery stenosis and atherosclerosis imaging. Invasive coronary angiography is the reference standard for stenosis assessment but cannot characterize coronary plaques. Finally, intravascular ultrasonography and optical coherence tomography are the most important invasive imaging modalities for the identification of plaques at high risk of rupture. The recommendations made in this Consensus Statement will help clinicians to choose the most appropriate imaging modality on the basis of the specific clinical scenario, individual patient characteristics and the availability of each imaging modality.In this Consensus Statement, Dewey and the other members of the Quantitative Cardiovascular Imaging Study Group provide clinical consensus recommendations on the optimal use of different imaging techniques in various patient populations to detect and assess coronary artery stenosis and atherosclerosis.

Although arterial and venous thromboembolic disorders are among the most frequent causes of mortality and morbidity, there has been little description of how the composition of thrombi and emboli depends on their vascular origin and age. We quantified the structure and composition of arterial and venous thrombi and pulmonary emboli using high-resolution scanning electron microscopy. Arterial thrombi contained a surprisingly large amount of fibrin, in addition to platelets. The composition of pulmonary emboli mirrored the most distal part of venous thrombi from which they originated, which differed from the structure of the body and head of the same thrombi. All thrombi and emboli contained few biconcave red blood cells but many polyhedrocytes or related forms of compressed red blood cells, demonstrating that these structures are a signature of clot contraction in vivo . Polyhedrocytes and intermediate forms comprised the major constituents of venous thrombi and pulmonary emboli. The structures within all of the thrombi and emboli were very tightly packed, in contrast to clots formed in vitro . There are distinctive, reproducible differences among arterial and venous thrombi and emboli related to their origin, destination and duration, which may have clinical implications for the understanding and treatment of thrombotic disorders.

Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits. Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.

Blood clots, which are composed of blood cells and a stabilizing mesh of fibrin fibers, are critical in cessation of bleeding following injury. However, their action is transient and after performing their physiological function they must be resolved through a process known as fibrinolysis. Internal fibrinolysis is the degradation of fibrin by the endogenous or innate presence of lytic enzymes in the bloodstream; under healthy conditions, this process regulates hemostasis and prevents bleeding or clotting. Fibrin-bound tissue plasminogen activator (tPA) converts nearby plasminogen into active plasmin, which is bound to the fibrin network, breaking it down into fibrin degradation products and releasing the entrapped blood cells. It is poorly understood how changes in the fibrin structure and lytic protein ratios influence the biochemical regulation and behavior of internal fibrinolysis. We used turbidity kinetic tracking and microscopy paired with mathematical modeling to study fibrin structure and lytic protein ratios that restrict internal fibrinolysis. Analysis of simulations and experiments indicate that fibrinolysis is driven by pore expansion of the fibrin network. We show that this effect is strongly influenced by the ratio of fibrin:tPAwhen compared to absolute tPA concentration. Thus, it is essential to consider relative protein concentrations when studying internal fibrinolysis both experimentally and in the clinic. An improved understanding of effective internal lysis can aid in development of better therapeutics for the treatment of bleeding and thrombosis.