Atherosclerotic Lesions In Patients Research Articles

Use of Rotational Atherectomy-Assisted Balloon Angioplasty in the Treatment of Isolated Below-the-Knee Atherosclerotic Lesions in Patients with Chronic Limb-Threatening Ischemia.

The aim of the study is to evaluate the safety and effectiveness of rotational atherectomy-assisted balloon angioplasty (BTK-RA) for the treatment of isolated below the knee (BTK) atherosclerotic lesions and to compare the outcomes to plain old balloon angioplasty (POBA). Between January 2020 and September 2023, 96 consecutive patients with chronic limb threatening ischemia (CTLI) and isolated BTK-lesions underwent POBA (group A) or BTK-RA (group B). The primary outcome measures were: periprocedural technical success, primary patency, postoperative increase of the ankle branchial index (ABI), target lesion revascularization (TLR), limb salvage, minor amputation and death. Both techniques had similar technical success, operative time, intraprocedural complications and bailout stent implantations, independently of the operator's experience. Group B had significantly higher primary patency rates (93.5% vs. 72.0%, respectively, p = 0.006), TLR (2.1% vs. 24%, p = 0.057), lower in-hospital stay (2.0-3.0 vs. 4.0-6.0 days, respectively, p < 0.001) and higher postoperative ABI (0.8-0.2 vs. 0.7-0.1, respectively, p = 0.008), compared to group A. Significant differences (POBA n: 20, 40%, BTK-RA n = 3, 6.5%) were found in minor amputation rates between the two groups (p < 0.001), while the respective limb salvage rates were similar in both groups (94.0% vs. 97.8%, p = 0.35). The use of BTK-RA for the treatment of BTK-lesions in patients with CTLI showed significant clinical advantages in comparison to POBA.

Atherosclerotic plaque composition and specific endovascular considerations in the end stage renal disease patients: a narrative review.

Vascular calcification (VC) and resulting vascular disease is one of the major causes of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). CKD itself is increasingly recognized as a risk factor for cardiac and peripheral arterial disease (PAD). This paper examines the atherosclerotic plaque composition and specific endovascular considerations in the end stage renal disease (ESRD) patients. The literature was reviewed regarding the current status of medical and interventional management arteriosclerotic disease in patients with CKD. Lastly, three representative cases displaying typical endovascular treatment options are provided. A literature search was performed in PubMed covering publications up to September 2021 as well as discussion with experts in the field. The high prevalence of atherosclerotic lesions in patients with chronic renal failure and high (re-)stenosis cause problems in the medium and long term as vascular calcium load represents one of the most widely encountered predictors of failure of endovascular treatment of PAD and future cardiovascular events (e.g., coronary calcium score). Patients with CKD also suffer from a greater risk for major vascular adverse events in general and worse revascularization outcomes following peripheral vascular intervention. A correlation between calcium burden and drug-coated balloon (DCB) performance has been established for PAD necessitating the need for different tools to cope with vascular calcium such as endoprosthesis or braided stents. Patients with CKD are at a higher risk of developing contrast-induced nephropathy (CIN). In addition to recommendations such as the administration of intravenous fluids, carbon dioxide (CO2) angiography is one option to potentially provide an effective and safe alternative both to iodine-based contrast media allergy and to the use of iodine-based contrast media in patients with CKD. Management and endovascular procedures of patients with ESRD are complex. In the course of time, new endovascular therapy methods have been developed such as directional atherectomy (DA) and the so-called "pave-and-crack" technique to deal with high vascular calcium burden. Besides interventional therapy, vascular patients with CKD benefit from aggressive medical management.

Neutrophil and lymphocyte count as predictors of the location of calcific coronary lesions in patients treated with rotational atherectomy.

The role of immune system activation in development and progression of atherosclerotic plaques has been postulated. Previous studies on inflammation have focused on the severity of coronary disease, the risk of acute coronary syndrome, and the prediction of outcomes based on hematological indices obtained from whole blood count analysis. To analyze simple data of the whole blood count in relation to the location of calcified atherosclerotic lesions in patients treated with coronary rotational atherectomy (RA). Eighty-one patients (57 (70%) males, mean (SD) age of 70.4 ±8 years) who underwent RA were enrolled in the study. The study group was divided into two subgroups depending on the proximal (group 1) and non-proximal (group 2) location of the culprit lesions in coronary arteries. The angiographic results were compared with demographic and clinical data and whole blood count analysis. The multivariable analysis revealed the predictive value of low neutrophil (OR = 0.75, 95% CI: 0.58-0.97, p = 0.030) and lymphocyte counts (OR = 0.27, 95% CI: 0.11-0.68, p = 0.005) for the proximal location of the culprit lesions. In the ROC analysis, combined neutrophil and lymphocyte counts showed the best prediction of proximal location, with the area under the curve of 0.747 (p < 0.001), yielding a sensitivity of 79.07% and specificity of 73.68%. The lower neutrophil and lymphocyte counts in peripheral blood count analysis may be more representative of proximal calcified coronary lesions. The relationship between neutrophil and lymphocyte blood count and calcific atherosclerotic plaque location can indicate the inflammatory background of epicardial atheroma formation and distribution.

Clinical features and metabolic reprogramming of atherosclerotic lesions in patients with chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) patients may present with atherosclerotic lesions in their pulmonary arteries, but their clinical characteristics remain unclear. The metabolic pathways associated with the atherosclerotic lesions may explain their occurrence and have implications for interventions, but they have not been investigated. We collected pulmonary endarterectomy (PEA) samples of CTEPH patients from December 2016 to August 2021. Following a detailed pathological examination of the PEA specimen, the patients were divided into those with and without lesions, and age- and sex matching were performed subsequently using propensity score matching (n = 25 each). Metabolomic profiling was used to investigate the metabolites of the proximal lesions in the PEA specimens. In our study population, 27.2% of all PEA specimens were found to contain atherosclerotic lesions. CTEPH patients with atherosclerotic lesions were more likely to have a history of symptomatic embolism and had a longer timespan between embolism and surgery, whereas the classic risk factors of systemic and coronary circulation could not distinguish CTEPH patients with or without atherosclerotic lesions. Metabolomic profiling revealed that the formation of atherosclerotic lesions in CTEPH was closely related to altered glycine, serine, and threonine metabolic axes, possibly involved in cellular senescence, energy metabolism, and a proinflammatory microenvironment. The occurrence of atherosclerotic lesions in the pulmonary arteries of CTEPH was associated with symptomatic thromboembolic history and prolonged disease duration. The results revealed a new link between atherosclerotic lesions and aberrant amino acid metabolism in the context of CTEPH for the first time. This study has characterized the clinical and metabolic profiles of this distinct group of CTEPH patients, providing new insights into disease pathogenesis and potential interventions.

Preprocedural Prediction of Underlying Atherosclerotic Lesions in Cerebral Large-Vessel Occlusions: Clinical Backgrounds, Radiological Findings, and Treatment Outcomes.

Mechanical thrombectomy using a standard device has been effective for acute cerebral large-vessel occlusions, particularly those due to cardiogenic embolism. However, evidence for those with underlying atherosclerotic lesions is lacking. In this study, we evaluated the predictive factors, treatment details, and outcomes of acute cerebral large-vessel occlusions with underlying atherosclerotic lesions in patients who underwent mechanical thrombectomy. We retrospectively analyzed consecutive patients with acute large-vessel occlusions who underwent mechanical thrombectomy at our institution between August 2014 and May 2021. Predictive factors of underlying atherosclerotic lesions were evaluated using univariate and multivariate analyses. In addition, treatment details and outcomes were evaluated and compared with those of other etiologies. Among 322 included patients, 202 (62.7%) were males and 65 (20.2%) had underlying atherosclerotic lesions. Multivariate analysis identified dyslipidemia, lack of arterial fibrillation documented on admission, smoking, internal carotid artery lesions, and stenosis ≥ 25% in non-occluded large vessels as predictive factors of underlying atherosclerotic lesions. Regarding treatment for underlying atherosclerotic lesions, the need for percutaneous transluminal angioplasty, stent placement, medical therapy, and longer procedure time were observed, while successful reperfusion rates, favorable outcomes, and mortality rates showed no significant differences with those of other etiologies. Coexisting diseases and radiological findings were useful for predicting underlying atherosclerotic lesions. Further understanding these characteristics may lead to the early detection of underlying atherosclerotic lesions, optimal treatment strategies, and better outcomes.

Lipopolysaccharides and Cellular Senescence: Involvement in Atherosclerosis.

Atherosclerosis is a chronic inflammatory disease of the vascular walls related to aging. Thus far, the roles of cellular senescence and bacterial infection in the pathogenesis of atherosclerosis have been speculated to be independent of each other. Some types of macrophages, vascular endothelial cells, and vascular smooth muscle cells are in a senescent state at the sites of atherosclerotic lesions. Likewise, bacterial infections and accumulations of lipopolysaccharide (LPS), an outer-membrane component of Gram-negative bacteria, have also been observed in the atherosclerotic lesions of patients. This review introduces the integration of these two potential pathways in atherosclerosis. Previous studies have suggested that LPS directly induces cellular senescence in cultured monocytes/macrophages and vascular cells. In addition, LPS enhances the inflammatory properties (senescence-associated secretory phenotype [SASP]) of senescent endothelial cells. Thus, LPS derived from Gram-negative bacteria could exaggerate the pathogenesis of atherosclerosis by inducing and enhancing cellular senescence and the SASP-associated inflammatory properties of specific vascular cells in atherosclerotic lesions. This proposed mechanism can provide novel approaches to preventing and treating this common age-related disease.

Deletion of Macrophage-Specific Glycogen Synthase Kinase (GSK)-3α Promotes Atherosclerotic Regression in Ldlr-/- Mice.

Recent evidence from our laboratory suggests that impeding ER stress–GSK3α/β signaling attenuates the progression and development of atherosclerosis in mouse model systems. The objective of this study was to determine if the tissue-specific genetic ablation of GSK3α/β could promote the regression of established atherosclerotic plaques. Five-week-old low-density lipoprotein receptor knockout (Ldlr−/−) mice were fed a high-fat diet for 16 weeks to promote atherosclerotic lesion formation. Mice were then injected with tamoxifen to induce macrophage-specific GSK3α/β deletion, and switched to standard diet for 12 weeks. All mice were sacrificed at 33 weeks of age and atherosclerosis was quantified and characterized. Female mice with induced macrophage-specific GSK3α deficiency, but not GSK3β deficiency, had reduced plaque volume (~25%) and necrosis (~40%) in the aortic sinus, compared to baseline mice. Atherosclerosis was also significantly reduced (~60%) in the descending aorta. Macrophage-specific GSK3α-deficient mice showed indications of increased plaque stability and reduced inflammation in plaques, as well as increased CCR7 and ABCA1 expression in lesional macrophages, consistent with regressive plaques. These results suggest that GSK3α ablation promotes atherosclerotic plaque regression and identify GSK3α as a potential target for the development of new therapies to treat existing atherosclerotic lesions in patients with cardiovascular disease.

Stroke risk stratification in elderly patients with comorbid sarcopenia and atherosclerosis

The study was to investigate the features of carotid arteries atherosclerosis as the leading risk factor for atherothrombotic stroke in elderly patients depending on the presence of sarcopenia. 2 groups of patients above the working age were examined: 110 patients with normal muscle mass and 24 suffering sarcopenia. Ultrasound examination of carotid and vertebral arteries extracranial segments was performed with an assessment of atherosclerotic changes severity, atherosclerotic plaques instability, 10-year risk of stroke (according to Framingham risk score) and a 10-year risk of fatal cardiovascular disease (SCORE risk scale). 10-year risk of fatal cardiovascular disease was 3 [2; 5] points for patients without sarcopenia, 3 [2; 3] points for patients with sarcopenia (p=0.81). The 10-year risk of stroke was 16 [12; 18] for patients without sarcopenia, 18 [15; 22] points for patients with sarcopenia (p=0.1). Due to the ultrasound examination data the incidence of carotid arteries atherosclerotic lesions in patients without sarcopenia was 50 (46.3%), in patients with sarcopenia - 18 (75.0%) (p=0.01). Statistically significant (p<0.05) increase in the atherosclerotic plaques instability signs was revealed in patients suffering sarcopenia compared to those without it: heterogeneous echotexture - 66.7% cases versus 38.2% (p=0.01), presence of hypoechoic masses - 41.7% patients vs 12.7% (p=0.02). It is important to take into account not only traditional risk factors in the overall assessment of cardiovascular risk as well as therapeutic and preventive measures planning in elderly patients, but also pay attention to body composition since modern diagnostic systems may be not sensitive enough to identify high-risk patients with comorbid atherosclerosis and sarcopenia.

Поєднане атеросклеротичне ураження у хворих на цукровий діабет 2-го типу

Актуальність. Значна поширеність атеросклерозу та його ускладнень у хворих на цукровий діабет (ЦД) 2-го типу визначає необхідність в подальших дослідженнях існуючих факторів ризику. Мета дослідження. Визначити вплив різних факторів ризику на розвиток атеросклеротичного ураження у хворих на ЦД 2-го типу. Матеріали й методи. Проаналізовані в динаміці впродовж 5 років середні показники систолічного артеріального тиску (САТ), HbA1c, високочутливого С-реактивного білка (вчСРБ), сечової кислоти (СК), холестерину ліпопротеїнів низької щільності (ХС ЛПНЩ) у сироватці крові та бали за шкалою тривоги та депресії HADRS у зіставленні з оцінкою ультразвукових даних щодо атеросклеротичного ураження сонних артерій (товщина комплексу інтима-медіа ≥ 0,9 мм чи наявність атеросклеротичних бляшок) та артерій нижніх кінцівок (кісточково-плечовий індекс ≤ 0,9) у 122 хворих на ЦД 2-го типу (66 жінок, 56 чоловіків; середній вік — 55,0 (49,8–62,0) року). Статистичний аналіз проведений за допомогою IBM SPSS Statistics 20. Результати. У ході дослідження хворі були поділені на 3 групи: I група — 48 осіб із атеросклеротичним ураженням сонних артерій та нижніх кінцівок, II група — 47 осіб із атеросклерозом сонних артерій, III група — 27 осіб без ознак атеросклеротичного ураження. Виявлено, що у хворих I групи середні рівні САТ (141,7 (132,1–152,9) мм рт.ст.), HbA1c (9,2 (8,2–9,9) %), вчСРБ (5,8 (4,2–6,9) мг/л) та СК (358,1 (302,4–396,1) мкмоль/л), ХС ЛПНЩ (4,1 (3,6–5,2) ммоль/л), балів за шкалою HADRS (16,0 (9,0–18,8) бала) були вірогідно вищими порівняно з показниками III групи (САТ — 136,7 (128,3–143,3) мм рт.ст., HbA1c — 7,7 (7,0–8,4)%, вчСРБ — 2,7 (1,1–3,3) мг/л, СК — 276,8 (227,0–316,0) мкмоль/л, ХС ЛПНЩ — 3,3 (3,0–4,0) ммоль/л, за шкалою HADRS — 8,0 (7,0–10,0) бала) (р &lt; 0,05). Середні рівні HbA1c та вчСРБ хворих I групи були вірогідно вищіми порівняно з показниками II групи (HbA1c — 8,7 (7,6–9,3) %, вчСРБ — 4,2 (3,0–5,3) мг/л) (р &lt; 0,05). Висновок. У хворих на ЦД 2-го типу з вищими середніми рівнями САТ, вчСРБ, HbA1c, СК, ХС ЛПНЩ та тривожно-депресивними порушеннями захворювання супроводжується більш частим виникненням атеросклеротичного ураження, у тому числі поєднаного ураження артерій різних басейнів.

Browning of White Adipose Tissue as a Therapeutic Tool in the Fight against Atherosclerosis.

Despite continuous medical advances, atherosclerosis remains the prime cause of mortality worldwide. Emerging findings on brown and beige adipocytes highlighted that these fat cells share the specific ability of non-shivering thermogenesis due to the expression of uncoupling protein 1. Brown fat is established during embryogenesis, and beige cells emerge from white adipose tissue exposed to specific stimuli like cold exposure into a process called browning. The consecutive energy expenditure of both thermogenic adipose tissues has shown therapeutic potential in metabolic disorders like obesity and diabetes. The latest data suggest promising effects on atherosclerosis development as well. Upon cold exposure, mice and humans have a physiological increase in brown adipose tissue activation and browning of white adipocytes is promoted. The use of drugs like β3-adrenergic agonists in murine models induces similar effects. With respect to atheroprotection, thermogenic adipose tissue activation has beneficial outcomes in mice by decreasing plasma triglycerides, total cholesterol and low-density lipoproteins, by increasing high-density lipoproteins, and by inducing secretion of atheroprotective adipokines. Atheroprotective effects involve an unaffected hepatic clearance. Latest clinical data tend to find thinner atherosclerotic lesions in patients with higher brown adipose tissue activity. Strategies for preserving healthy arteries are a major concern for public health.

Biomarkers of Carotid Stenosis

Early recognition of rupture-prone atherosclerotic lesions in patients with high-graded carotid stenosis is an important clinical problem for preventing ischemic stroke. Various pathophysiological mechanisms are responsible for the progression and instability of plaques, such as changes in lipid composition, infiltration by immunoinflammatory cells and degradation of the extracellular matrix of the vascular wall by matrix metalloproteinases, enhanced inflammatory response and plaque neovascularization. These features are the main cause of plaque rupture and, as a consequence, neurologic symptoms. Therefore, matrix metalloproteinases and inflammatory factors can serve as possible markers for patients with severe unstable stenosis of carotid arteries. Due to the heterogeneity of atherosclerotic lesions, only one biomarker is not enough to reliably predict the development of a stroke. The use of a combination of biomarkers is better correlated with clinical data and, therefore, exceeds the analysis of individual factors. To increase the overall sensitivity and specificity and more reliable diagnosis of stroke in patients with symptomatic and asymptomatic carotid stenosis, the biomarker panel should include independent biomarkers. Further preclinical experiments and clinical trials are needed to assess the significance and precise definition of the threshold levels of such biomarkers before they can be used in clinical practice.

Similarities and differences in ultrasound of extracranial brachiocephalic atherosclerotic lesions in patients with ischemic anterior and posterior circulation stroke

Aim. To establish similarities and differences in ultrasound of extracranial brachiocephalic atherosclerotic lesions in patients with ischemic anterior and posterior circulation stroke.Material and methods. The study involved 668 patients (men, 370; women, 298) with carotid territory IS aged 63±11 and 69±9 years, respectively, and 235 patients (men, 129; women, 106) with vertebrobasilar (VB) territory IS aged 59±12 and 63±10 years, respectively, who underwent duplex ultrasound.Results. Atherosclerotic plaques (ASP) in the internal carotid arteries (ICA) were diagnosed significantly more often (p&lt;0,05) (right ICA (ICAr) — 44,0% of cases; left ICA (ICAl) — 48,4%) and the degree of stenosis of ICA mouths was significantly higher (p&lt;0,05) (ICAr —53±23%, ICAl — 54±24%) in carotid territory IS than in VB territory IS (ICAr — 34,0% of cases; average degree of stenosis — 47±18%; ICAl — 33,6%, average degree of stenosis — 46±18%. There were no significant differences in the prevalence of ASP in vertebral arteries and related stenosis in IS in both territories. Also, there were no significant intergroup differences in the prevalence of homogeneous anechoic or hypoechoic and heterogeneous with hypoechoic predominance ASPs in the ICA mouths: in carotid territory IS, such ASPs were detected in each ICA in 33,5% of cases; in VB territory IS, in 29,6% of cases.Conclusion. In patients with carotid and VB territory IS, risky ASPs were recorded with the same frequency, while the overall prevalence of ASPs and the stenosis degree of ICA mouths was significantly higher in carotid IS.

Mulberry leaf attenuates atherosclerotic lesions in patients with coronary heart disease possibly via 1-Deoxynojirimycin: A placebo-controlled, double-blind clinical trial.

Mulberry leaf tea reduces atherosclerotic lesions and its main component is Deoxynojirimycin (DNJ). We aimed to explore the effects of Mulberry leaf DNJ (MLD) on atherosclerotic lesions in the patients with coronary heart disease (CHD). MLD and serum DNJ was detected by high-performance liquid chromatography (HPLC). The CHD patients with low-density lipoprotein cholesterol>140mg/dl were assigned into the EG (MLD treatment) and the CG (placebo treatment) groups. Serum biochemical indices, the cerebrovascular and cardiovascular events and carotid intima-media thickness (IMT) were measured before and after a 1-year intervention. Pearson Correlation Coefficient test was used to explore the relationship between serum levels of DNJ and IMT values. Serum DNJ was 70±50ng/ml in the EG group but no serum DNJ was detected in the CG group. The incidence of cerebrovascular and cardiovascular events in the EG was lower than that in the CG group (p<.05). MLD therapy improved antioxidant and anti-inflammatory properties and serum lipid profile (p<.05). The IMT values in the EG group were lower than those in the CG group (p<.05). Serum levels of DNJ had a strong negative relationship with IMT values. MLD treatment attenuates atherosclerotic lesions possibly via DNJ. PRACTICAL APPLICATIONS: Mulberry leaves Deoxynojirimycin (MLD) treatment improved antioxidant and anti-inflammatory properties and serum lipid profile in heart disease patients. MLD reduce carotid intima-media thickness (IMT) and serum levels of DNJ (the main ingredient of mulberry leaf) had a strong relationship with IMT values. MLD is an amazing treat used for reducing the incidence of cerebrovascular and cardiovascular events in heart disease patients.

Outside-in signaling by femoral cuff injury induces a distinct vascular lesion in adipose triglyceride lipase knockout mice.

Genetic deficiency of adipose triglyceride lipase (ATGL), a rate-limiting enzyme for intracellular triglyceride (TG) hydrolysis, causes TG-deposit cardiomyovasculopathy (TGCV), a recently identified rare cardiovascular disorder (ORPHA code: 565612) in humans. One of the major characteristics of TGCV is a novel type of diffuse and concentric coronary atherosclerosis with ATGL-deficient smooth muscle cells (SMCs). Patients with TGCV have intractable coronary artery disease. Therefore, it is crucial to investigate the mechanisms underlying vascular lesions in ATGL deficiency using animal models. Cuff injury is an experimental procedure to induce vascular remodeling with neointimal formation with SMCs after placing a cuff around the adventitial side of the artery without direct influence on endothelium. We report the effect of cuff injury on femoral arteries of ATGL-knockout (ATGL⁻/⁻) mice. Cuff-induced concentric neointimal formation with migrating SMCs was exacerbated in ATGL⁻/⁻ mice, mimicking atherosclerotic lesions in patients with TGCV. In the media, cell death of SMCs and loss of elastic fibers increased. Perivascular infiltrating cells expressing tumor necrosis factor-α (TNF-α) were more prominent in ATGL⁻/⁻ mice than in wild-type (WT) mice. In Boyden chamber experiments, a greater number of ATGL⁻/⁻ SMCs migrated in response to TNF-α compared to WT SMCs. These data, for the first time, demonstrated that outside-in signaling by cuff-induced neointimal formation where paracrine stimuli from adventitial infiltrating cells may lead to neointimal formation and mediolysis in ATGL-deficient conditions. Cuff injury might be a valuable model for understanding the mechanisms underlying the development of atherosclerotic lesions in patients with TGCV.

Evaluation of intracranial and extracranial atherosclerotic lesions in patients with symptomatic coronary artery disease

ABSTRACT Objectives Patients with coronary artery disease (CAD) concomitant with extracranial and intracranial atherosclerotic disease (EICAD) may have an increased risk of stroke and myocardial ischemic events. This study aimed to evaluate the concomitant atherosclerotic lesions in extra- and intracranial arterial beds in patients with CAD. Methods A total of 1274 patients who underwent coronary angiography due to ischemic heart disease were included. All patients underwent ultrasound screening of the extra- and intracranial arteries before coronary angiography, and the degrees of extracranial carotid artery disease (ECAD) and intracranial cerebral artery disease (ICAD) were recorded. Results A total of 1062 cases of CAD were confirmed. The prevalence of ECAD, ICAD, and EICAD (ECAD combined with ICAD) in patients with CAD was 15.6%, 11.2% and 11.9%, respectively. For patients with 3-vessel disease, the prevalence was 20.5%, 13.8% and 18.1%, and for patients with severe coronary artery stenosis, the prevalence was 15.8%, 12.1% and 13.2%, respectively. The presence and extent of ECAD and ICAD were positively correlated with the number of lesion vessels and degree of CAD. The posterior circulation arteries were more prone to lesions in patients with ECAD, while the anterior circulation arteries were more vulnerable to lesions in patients with ICAD. Conclusions The prevalence of ECAD, ICAD and EICAD is high in patients with CAD, and the presence of these conditions is positively correlated with the extent and degree of CAD. Evaluations of ECAD and ICAD should be highly recommended for CAD patients to reduce the future risk of cardiovascular diseases.

DISCRETE LABORATORY AND MORPHOMETRIC MARKERS OF ATHEROSCLEROTIC LESIONS OF LOWER EXTREMITY VESSELS

The aim: To investigate discrete laboratory and morphometric features of atherosclerotic lesions in patients with chronic ischemia of the lower extremities (CILE). Materials and methods:The examined contingent consisted of 47 patients (age 56.32 ± 1.09 years) diagnosed with obliterating atherosclerosis of the lower extremities. The study included determination of levels of Homocysteine, Folic acid, C protein, quantitative determination of circulating Endothelial cells (DEC) in blood plasma, and morphometric study of DEC. Results: Protein C levels are within the reference values (0.97 ± 0.12 mg / l. In 37 (78.7%) patients Hypoacidofoliemia (<3.0 mmol / l) was observed. Homocysteine levels were clearly elevated in all patients. In the vast majority Hyperhomocysteinemia mild form (91.5%) was observed. The number of DEC in patients was -3.22 ± 0.39x105/l and after compression -6.12 ± 0.21x105/l. Conclusions: Protein C levels were within the reference values (0.97 ± 0.12 mg / l); Folic acid levels in the vast majority (37 patients, 78.7%) were <3.0 mmol /l. Blood plasma Homocysteine levels were clearly elevated in all patients. The mild form of Hyperhomocysteinemia (91.5%). was observed in the vast majority The number of DEC in patients was -3.22 ± 0.39x105 and after compression -6.12 ± 0.21x105/l, which confirmed the presence of the endothelial dysfunction.

P977 CT phenotype of high-risk atherosclerotic plaques causing an acute coronary syndrome compared to silent vulnerable plaques

Abstract Funding Acknowledgements PlaqueImage.- research grant no. 103544/2016, contract number 26/01.09.2016 - Background Previous studies demonstrated that plaque morphology has a crucial role in the development of an acute coronary syndrome (ACS). However, not all vulnerable coronary plaques produce an ACS and the prediction power of various vulnerability features to predict an acute coronary event in a close future, has not been elucidated so far. Objective We aimed to use multi-slice computed tomography angiography (CTA) for assessment of morphological characteristics of culprit lesions producing an ACS in the next several months after CT assessment, in comparison with morphological characteristics of unstable coronary atherosclerotic plaques which did not trigger an ACS. Material and methods We analyzed 40 patients in whom CTA revealed presence of unstable coronary lesions, exhibiting at least one marker of vulnerability: napkin ring sign (NRS), spotty calcium (SC), positive remodeling (PR) or presence of low attenuation plaque (LAP), divided in 2 groups: group 1 - 20 patients who developed an ACS in the next 6 months following CTA examination, and group 2 – 20 patients matched for age, gender and risk factors, who did not present any cardiovascular event 6 month after CTA assessment. Post-processing of multi-slice CTA images was performed in order to assess morphological characteristics and CT-derived markers of atherosclerotic plaque instability. Results Similar mean values of plaque length (17.1 +/- 5.9 mm vs 16.9 +/- 3.4 mm; p = 0.6) and total atheroma volume (188.1 +/- 104.7 mm3vs 186.4 +/- 90.7 mm3; p = 0.8) were obtained for both groups. The mean number of vulnerability markers was 1.6 in group 1 vs 1.2 in group 2 (p = 0.07). However, atherosclerotic lesions in patients from group 1 presented significantly higher values of lipid-rich atheroma (9.8 +/- 10.8 mm3vs 2.6 +/- 1.0 mm3; p = 0.01) and remodeling index (1.14 +/- 0.3 in group 1 vs 0.89 +/- 0.19 in group 2, p = 0.04). At the same time, atheromatous plaques in patients who developed an ACS during the 6-months follow-up showed in a significantly higher proportion LAP (45% in group vs 10% in group 2, p = 0.03) and PR (15%in group 1 versus 5% in group 2, p = 0.04), but not NRS (30% vs 25%, p = ns) or SC (65% vs 40%, p = 0.2). Conclusions Atherosclerotic plaques producing an ACS exhibit a different phenotype than unstable plaques that remain silent. The CTA profile of atheromatous plaques producing an ACS includes the presence of low attenuation, positive remodeling, higher RI and lipid-rich atheroma. Presence of these features in high-risk coronary plaques identifies very high risk patients, who can benefit from adapted therapeutic strategy in order to prevent the development of an ACS.

P4402Effect of carnitine supplementation on progression of carotid plaque in the metabolic syndrome: the ECoM study

Abstract Background/Introduction L-carnitine (L-C) has been investigated as a potential therapy for cardiovascular (CV) disease, but its direct effects on human atherosclerosis are unknown. Epidemiological studies suggest a possible reduction of CV risk factors following treatment, whereas animal studies have shown that L-C may increase pro-atherogenic metabolites. Purpose The purpose of this study was to determine whether L-C therapy led to atherosclerosis progression or regression by direct quantification of carotid atherosclerotic lesions in patients with metabolic syndrome (MetS). Methods This study was a Phase 2, prospective, parallel, double blinded, randomized, placebo-controlled, two-center trial. MetS was defined according to the International Diabetes Federation harmonized definition, where presence of any 3 of the 5 following risk factors constituted a diagnosis: elevated waist circumference; elevated triglycerides; reduced HDL or treated; elevated blood pressure or treated; elevated glucose or HbA1c or treated. Participants with a baseline carotid total plaque volume (TPV) ≥50 mm3 were randomized to placebo or 2 g L-C daily for 6 months. Plaque progression was quantified by 3D carotid ultrasound for change in TPV and reduction in vessel lumen area (% area stenosis, Fig. 1). Absolute differences were assessed on the raw scale, while percent change on the log scale. Analysis of covariance (ANCOVA) was used to assess within- and between-arm differences. Results Of the 177 participants randomized, 157 completed the study (L-C n=76, placebo n=81). No statistically significant difference between arms was found in the primary outcome (TPV). However, there was progression of plaque stenosis in the treatment arm: the L-C group had an increase in stenosis of 9.8% (p=0.01) higher than the placebo arm, and a 2.7% (p=0.03) greater absolute change. Total cholesterol and LDL levels (0.10 mmol/L and 0.05 mmol/L, respectively) were higher in the intervention arm compared to the placebo arm (−0.06 mmol/L and −0.07 mmol/L). Figure 1 Conclusions We observed progression of atherosclerosis with L-C therapy compared to placebo in patients with MetS. The clear lack of benefit of L-C therapy in this population raises serious concerns for its further use as a potential therapy. Given its association with pro-atherogenic metabolites our study offers further understanding of the atherosclerotic process. Acknowledgement/Funding Heart and Stroke Foundation of Canada

171Intravascular polarimetry in patients with coronary artery disease: a first-in-human pilot study

Abstract Background Polarization-sensitive (PS-) optical frequency domain imaging (OFDI) measures polarization properties of tissue together with conventional cross-sectional OFDI images of subsurface microstructure. PS-OFDI offers refined insight into plaque morphology and composition, which are implicated in the pathogenesis of acute coronary syndromes (ACS). Purpose This first-in-human pilot study of intravascular polarimetry aimed to investigate birefringence and depolarization features of coronary plaques in patients and to examine the relationship of these features with established structural characteristics available to conventional OFDI and with clinical presentation. Methods 30 patients undergoing PS-OFDI (acute coronary syndrome; ACS, n=12 and stable angina pectoris; SAP, n=18) participated in this study. 342 cross-sectional images evenly distributed along all imaged coronary arteries were classified into one of seven plaque categories according to conventional OFDI. Polarization features averaged over the entire intimal area of each cross-section were compared between plaque types and with structural parameters. Further, we assessed the polarization properties in the fibrous caps of ACS and SAP culprit lesions and compared them with structural features using a generalized linear model. Results The median birefringence and depolarization showed statistically significant differences among plaque types (both p&lt;0.001, one-way ANOVA). Depolarization significantly differed between individual plaque types (p&lt;0.05), except between fibro-fatty and fibro-calcified plaques. Caps of ACS lesions and ruptured caps exhibited lower birefringence than caps of SAP lesions (p&lt;0.01). In addition to clinical presentation, cap birefringence also associated with macrophage accumulation as assessed by normalized standard deviation. Intravascular polarimetry Conclusions Intravascular polarimetry provides quantitative metrics that help to characterize coronary arterial tissues and may offer refined insight into coronary arterial atherosclerotic lesions in patients (Figure). Quantitative assessment of plaque polarization properties by intravascular polarimetry may open new avenues for studying plaque progression and detecting high-risk patients. Acknowledgement/Funding The JSPS Overseas Research Fellowship, the Uehara Memorial Foundation, and the Japan Heart Foundation and Bayer Yakuhin

Intravascular Polarimetry in Patients With Coronary Artery Disease

ObjectivesThe aims of this first-in-human pilot study of intravascular polarimetry were to investigate polarization properties of coronary plaques in patients and to examine the relationship of these features with established structural characteristics available to conventional optical frequency domain imaging (OFDI) and with clinical presentation. BackgroundPolarization-sensitive OFDI measures birefringence and depolarization of tissue together with conventional cross-sectional optical frequency domain images of subsurface microstructure. MethodsThirty patients undergoing polarization-sensitive OFDI (acute coronary syndrome, n = 12; stable angina pectoris, n = 18) participated in this study. Three hundred forty-two cross-sectional images evenly distributed along all imaged coronary arteries were classified into 1 of 7 plaque categories according to conventional OFDI. Polarization features averaged over the entire intimal area of each cross section were compared among plaque types and with structural parameters. Furthermore, the polarization properties in cross sections (n = 244) of the fibrous caps of acute coronary syndrome and stable angina pectoris culprit lesions were assessed and compared with structural features using a generalized linear model. ResultsThe median birefringence and depolarization showed statistically significant differences among plaque types (p < 0.001 for both, one-way analysis of variance). Depolarization differed significantly among individual plaque types (p < 0.05), except between normal arteries and fibrous plaques and between fibrofatty and fibrocalcified plaques. Caps of acute coronary syndrome lesions and ruptured caps exhibited lower birefringence than caps of stable angina pectoris lesions (p < 0.01). In addition to clinical presentation, cap birefringence was also associated with macrophage accumulation as assessed using normalized SD. ConclusionsIntravascular polarimetry provides quantitative metrics that help characterize coronary arterial tissues and may offer refined insight into coronary arterial atherosclerotic lesions in patients.