Carotid Interventions for Women: The Hazards and Benefits

The goal of the current review is to examine the hazards and benefits of carotid interventions in women and to provide recommendations for the indications for carotid intervention in female patients. Stroke and cerebrovascular disease are prevalent in women. There are inherent biological and other differences in men and women, which affect the manifestations and outcome of stroke, with women experiencing worse disability and higher mortality following ischemic stroke than men. Due to the underrepresentation of female patients in most clinical trials, the ability to make firm but alternative recommendations for women specifically on the management of carotid stenosis is challenging. Although some data suggest that women might have worse periprocedural outcomes as compared to men following all carotid revascularization procedures, there is also an abundance of data to support a similar risk for carotid procedures in men and women, especially with carotid endarterectomy and transcarotid artery revascularization. Therefore, the indications for carotid revascularization are the same in women as they are in men. The choice of a carotid revascularization procedure in women is based upon the same factors as in men and requires careful evaluation of a particular patient’s risk profile, anatomic criteria, plaque morphology, and medical comorbidities that might favor one technique over the other. When performing carotid revascularization procedures in women, tailored techniques and procedures to address the small diameter of the female artery are warranted.

Comparison of Carotid Atherosclerotic Plaque Characteristics between Symptomatic Patients with Transient Ischemic Attack and Stroke using High-Resolution Magnetic Resonance Imaging

Background:This study aimed to compare the characteristics of carotid plaques between patients with transient ischemic attack (TIA) and ischemic stroke using magnetic resonance (MR) imaging.Methods：Patients with a recent ischemic stroke or TIA who exhibited atherosclerotic plaques of carotid arteries in the symptomatic sides determined by MR vessel wall imaging were recruited. The plaque morphology and compositions including intraplaque hemorrhage (IPH), lipid-rich necrotic-core (LRNC) and calcification were compared between TIA and stroke patients. Logistic regression was performed to relate the plaque characteristics to the types of ischemic events.Results:A total of 270 patients with TIA or ischemic stroke were recruited. Stroke patients had significantly higher prevalence of diabetes (42.2% vs. 28.2%, p=0.021), greater mean wall area (35.1 ± 10.1 mm2 vs. 32.0 ± 7.7 mm2, p = 0.004), mean wall thickness (1.3 ± 0.2 mm vs. 1.2 ± 0.2 mm, p=0.001), maximum normalized wall index (NWI)(63.9% ± 6.0% vs. 62.2% ± 5.9%, p=0.023) and %volume of LRNC (9.7%± 8.2% vs. 7.4% ±7.9%, p=0.025) in carotid arteries compared to those with TIA. After adjusted for clinical factors, above characteristics of carotid arteries were significantly associated with the type of ischemic events. After further adjusted for maximum NWI, this association remained statistically significant (OR, 1.41; CI, 1.01-1.96; p=0.041).Conclusions:Ischemic stroke patients had larger plaque burden and greater proportion of LRNC in carotid plaques compared to those with TIA. This study suggests that ischemic stroke patients had more vulnerable plaques compared to those with TIA.

Identification of Symptomatic Carotid Artery Plaque: A Three-Item Scale Combined Angiography With Optical Coherence Tomography

Introduction: Symptomatic carotid disease conveys a high risk of recurrent stroke. Plaque morphology and specific plaque characteristics are associated with the risk of stroke. This study aimed to evaluate the detailed plaque features by optical coherence tomography (OCT) and develop a simple scale combining clinical indicators, digital subtraction angiography (DSA), and OCT imaging markers to identify symptomatic carotid plaque.Methods: Carotid plaques from consecutive patients who underwent carotid OCT imaging between June 2017 and June 2021 were evaluated. Clinical characteristics, DSA, and OCT data were compared between the symptomatic and asymptomatic groups. Logistic regression was performed to identify the factors associated with symptomatic carotid plaque and to develop a scale. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the scale.Results: A total of 90 carotid plaques from 90 patients were included (symptomatic 35.6%, asymptomatic 64.4%). Three main factors were found to be associated with symptomatic carotid plaque: high-density lipoprotein cholesterol (HDL-C) <0.925 mmol/L (OR, 4.708; 95% CI, 1.640 to 13.517; P = 0.004), irregular plaque (OR, 4.017; 95% CI, 1.250 to 12.910; P = 0.020), and white thrombus (OR, 4.594; 95% CI, 1.141 to 18.487; P = 0.032). The corresponding score of three items produced a scale with good discrimination (AUC, 0.768; 95% CI, 0.665 to 0.871). The optimal cutoff value of the scale was 1.5 points with 59.4% sensitivity and 84.5% specificity.Conclusion: The three-item scale comprising HDL-C <0.925 mmol/L, angiographical irregular plaque, and white thrombus detected by OCT may provide information to identify symptomatic carotid plaque. Further large-scale studies are required to validate whether the symptomatic carotid plaque scale is clinically valuable in recognizing carotid atherosclerosis in the early stages.

713 Culprit plaque morphology and healing capacity in patients with and without preinfarction angina: an optical coherence tomography imaging study

Aims The relationship between culprit plaque morphology, healed culprit plaques prevalence and clinical presentation of acute myocardial infarction (AMI) remains largely unexplored. We hypothesized that angina preceding the occurrence of AMI (pre-infarction angina, PIA) may reflect a distinct morphologic phenotype of culprit plaques and potentially different healing capacity. Methods and results We conducted a retrospective observational study in patients with AMI who underwent intracoronary optical coherence tomography (OCT) imaging of the culprit lesion before PCI at the Fondazione Policlinico A. Gemelli–Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome. Based on the clinical history, patients were classified into two groups: (i) PIA group, defined as either intermittent chest pain within 6 h preceding the final episode of chest pain, or unstable angina (or both) in the week preceding AMI or (ii) no-PIA group, defined as a single episode of chest pain without prodromal symptoms in the preceding week. Culprit plaques were classified as plaque rupture (PR) or intact fibrous cap (IFC), and presence of layered appearance (healed plaque, HP) was assessed. Thrombus burden (TB) was estimated, and prevalence of diffuse calcification, neovascularization, and OCT-defined macrophage accumulation were evaluated. A total of 102 patients with AMI were included (50 PIA, 52 no-PIA). Patients with PIA showed a higher prevalence of IFC than PR (58% vs. 42%, P = 0.030). PR in patients with PIA were more frequently associated with macrophage accumulation (71.4% vs. 28.6% P = 0.001), and TB tended to be lower [22.0 (15.8–30.3) vs. 38.5 (12.8–67.5), P = 0.145]. Diffuse calcifications were significantly less frequent in patients with PIA (22.0% vs. 40.4%, P = 0.045), while neovascularization tended to be more frequent (58.0% vs. 42.3%, P = 0.113). HPs prevalence was significantly higher in the PIA than in the no-PIA group (66.0% vs. 25.0%, P < 0.001). Conclusions Patients with PIA have a distinct culprit plaque phenotype, more frequently characterized by IFC and a relatively lower TB, with a significantly higher prevalence of plaque healing.

SUR1-E1506K mutation impairs glucose tolerance and promotes vulnerable atherosclerotic plaque phenotype in hypercholesterolemic mice

Background and aims Diabetes is a major risk factor of atherosclerosis and its complications. The loss-of-function mutation E1506K in the sulfonylurea receptor 1 (SUR1-E1506K) induces hyperinsulinemia in infancy, leading to impaired glucose tolerance and increased risk of type 2 diabetes. In this study, we investigate the effect of SUR1-E1506K mutation on atherogenesis in hypercholesterolemic LDLR-/- mice. Methods SUR1-E1506K mutated mice were cross-bred with LDLR-/- mice (SUR1Δ/LDLR-/-), 6 months old mice were fed a western-diet (WD) for 6 months to induce advanced atherosclerotic plaques. At the age of 12 months, atherosclerosis and plaque morphology were analyzed and mRNA gene expression were measured from aortic sections and macrophages. Glucose metabolism was characterized before and after WD. Results were compared to age-matched LDLR-/- mice. Results Advanced atherosclerotic plaques did not differ in size between the two strains. However, in SUR1Δ/LDLR-/- mice, plaque necrotic area was increased and smooth muscle cell number was reduced, resulting in higher plaque vulnerability index in SUR1Δ/LDLR-/- mice compared to LDLR-/- mice. SUR1Δ/LDLR-/- mice exhibited impaired glucose tolerance and elevated fasting glucose after WD. The positive staining area of IL-1β and NLRP3 inflammasome were increased in aortic sections in SUR1Δ/LDLR-/- mice compared to LDLR-/- mice, and IL-18 plasma level was elevated in SUR1Δ/LDLR-/- mice. Finally, the mRNA expression of IL-1β and IL-18 were increased in SUR1Δ/LDLR-/- bone marrow derived macrophages in comparison to LDLR-/- macrophages in response to LPS. Conclusions SUR1-E1506K mutation impairs glucose tolerance and increases arterial inflammation, which promotes a vulnerable atherosclerotic plaque phenotype in LDLR-/- mice.

Optical Coherence Tomography-Derived Changes in Plaque Structural Stress Over the Cardiac Cycle: A New Method for Plaque Biomechanical Assessment

Introduction: Cyclic plaque structural stress has been hypothesized as a mechanism for plaque fatigue and eventually plaque rupture. A novel approach to derive cyclic plaque stress in vivo from optical coherence tomography (OCT) is hereby developed.Materials and Methods: All intermediate lesions from a previous OCT study were enrolled. OCT cross-sections at representative positions within each lesion were selected for plaque stress analysis. Detailed plaque morphology, including plaque composition, lumen and internal elastic lamina contours, were automatically delineated. OCT-derived vessel and plaque morphology were included in a 2-dimensional finite element analysis, loaded with patient-specific intracoronary pressure tracing data, to calculate the changes in plaque structural stress (ΔPSS) on vessel wall over the cardiac cycle.Results: A total of 50 lesions from 41 vessels were analyzed. A significant ΔPSS gradient was observed across the plaque, being maximal at the proximal shoulder (45.7 [32.3, 78.6] kPa), intermediate at minimal lumen area (MLA) (39.0 [30.8, 69.1] kPa) and minimal at the distal shoulder (35.1 [28.2, 72.3] kPa; p = 0.046). The presence of lipidic plaques were observed in 82% of the diseased segments. Larger relative lumen deformation and ΔPSS were observed in diseased segments, compared with normal segments (percent diameter change: 8.2 ± 4.2% vs. 6.3 ± 2.3%, p = 0.04; ΔPSS: 59.3 ± 48.2 kPa vs. 27.5 ± 8.2 kPa, p < 0.001). ΔPSS was positively correlated with plaque burden (r = 0.37, p < 0.001) and negatively correlated with fibrous cap thickness (r = −0.25, p = 0.004).Conclusions: ΔPSS provides a feasible method for assessing plaque biomechanics in vivo from OCT images, consistent with previous biomechanical and clinical studies based on different methodologies. Larger ΔPSS at proximal shoulder and MLA indicates the critical sites for future biomechanical assessment.

Gender-based in-vivo comparison of culprit plaque characteristics and plaque microstructures using optical coherence tomography in acute coronary syndrome

Introduction: Women perform worse after acute coronary syndrome (ACS) than men. The reason for these differences is unclear. The aim was to ascertain gender differences in the culprit plaque characteristics in ACS. Methods:Patients with ACS undergoing percutaneous coronary intervention for the culprit vessel underwent optical coherence tomography (OCT) imaging. Culprit plaque was identified as lipid rich,fibrous, and calcific plaque. Mechanisms underlying ACS are classified as plaque rupture, erosion,or calcified nodule. A lipid rich plaque along with thin-cap fibroatheroma (TCFA) was a vulnerable plaque. Plaque microstructures including cholesterol crystals, macrophages, and microvessels were noted. Results: A total of 52 patients were enrolled (men=29 and women=23). Baseline demographic features were similar in both the groups except men largely were current smokers (P<0.001). Plaque morphology,men vs. women: lipid rich 88.0% vs. 90.5%; fibrous 4% vs 0%; calcific 8.0% vs. 9.5% (P = 0.64). Of the ACS mechanisms in males versus females; plaque rupture (76.9 % vs. 50 %), plaque erosion (15.4 % vs.40 %) and calcified nodule (7.7 % vs. 10 %) was noted (P = 0.139). Fibrous cap thickness was (50.19 ±11.17 vs. 49.00 ± 10.71 mm, P = 0.71) and thin-cap fibroatheroma (96.2% vs. 95.0%, P = 1.0) in men and women respectively. Likewise no significant difference in presence of macrophages (42.3 % vs. 30%, P = 0.76), microvessels (73.1% vs. 60 %, P = 0.52) and cholesterol crystals (92.3% vs. 80%, P = 0.38). Conclusion: No significant gender-based in-vivo differences could be discerned in ACS patients’ culprit plaques morphology, characteristics, and underlying mechanisms.