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1.
Stroke ; 51(9): 2761-2769, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32811377

RESUMO

BACKGROUND AND PURPOSE: Carotid plaque is a heritable trait and a strong predictor of vascular events. Several loci have been identified for carotid plaque, however, studies in minority populations are lacking. Within a multi-ethnic cohort, we have identified individuals with extreme total carotid plaque area (TCPA), that is, higher or lower TCPA than expected based on traditional vascular risk factors (age, sex, smoking, diabetes mellitus, hypertension, etc). We hypothesized that these individuals are enriched with genetic variants accounting for the plaque burden that cannot be explained by traditional vascular risk factors. Herein, we sought to identify the genetic basis for TCPA using the multi-ethnic cohort. METHODS: Three hundred forty participants (170 from each extreme group) from 3 race/ethnic groups (53% Hispanic, 29% non-Hispanic Black, and 18% non-Hispanic White) were genotyped using a genome-wide single-nucleotide polymorphism (SNP) array and imputed using 1000Genome data. SNP-based analyses using logistic regression and gene-based analyses using VEGAS2 were performed within each race/ethnic group and then meta-analyzed. Genes with P<0.001 were included in an overrepresentation enrichment pathway analysis using WebGestalt. Promising findings were tested for association with ischemic stroke using the MEGASTROKE Consortium data set. RESULTS: No SNP or gene reached genome-wide significance. In the pathway analysis, GO:0050913 (sensory perception of bitter taste) gene set was significantly enriched (P=4.5×10-6, false discovery rate=0.04), which was confirmed in MEGASTROKE (P=0.01). Within the GO:0050913 gene set, 3 genes were associated with extreme TCPA in our study (P<0.001): TAS2R20, TAS2R50, and ITPR3. In TAS2R50, rs1376251 is the top SNP and has been associated with myocardial infarction by others. In ITPR3, a SNP with high regulatory potential (rs3818527, RegulomeScore=1f), and ITPR3 itself were among the top SNP-based and gene-based results and showed consistent evidence for association in all ethnic groups (P<0.05). CONCLUSIONS: Extreme TCPA analysis identified new candidate genes for carotid plaque in understudied populations.


Assuntos
Doenças das Artérias Carótidas/genética , Placa Aterosclerótica/genética , Paladar/genética , Adulto , Grupo com Ancestrais do Continente Africano , Idoso , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/fisiopatologia , Dieta , Grupos Étnicos , Grupo com Ancestrais do Continente Europeu , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Hispano-Americanos , Humanos , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Fenótipo , Placa Aterosclerótica/epidemiologia , Placa Aterosclerótica/fisiopatologia , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Estados Unidos/epidemiologia
3.
Med Hypotheses ; 143: 110125, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32763657

RESUMO

The novel coronavirus (SARS-CoV-2) is primarily a respiratory pathogen and its clinical manifestations are dominated by respiratory symptoms, the most severe of which is acute respiratory distress syndrome (ARDS). However, COVID-19 is increasingly recognized to cause an overwhelming inflammatory response and cytokine storm leading to end organ damage. End organ damage to heart is one of the most severe complications of COVID-19 that increases the risk of death. We proposed a two-fold mechanism responsible for causing acute coronary events in patients with COVID-19 infection: Cytokine storm leading to rapid onset formation of new coronary plaques along with destabilization of pre-existing plaques and direct myocardial injury secondary to acute systemic viral infection. A well-coordinated immune response is the first line innate immunity against a viral infection. However, an uncoordinated response and hypersecretion of cytokines and chemokines lead to immune related damage to the human body. Human Coronavirus (HCoV) infection causes infiltration of inflammatory cells that cause excessive production of cytokines, proteases, coagulation factors, oxygen radicals and vasoactive molecules causing endothelial damage, disruption of fibrous cap and initiation of formation of thrombus. Systemic viral infections also cause vasoconstriction leading to narrowing of vascular lumen and stimulation of platelet activation via shear stress. The resultant cytokine storm causes secretion of hypercoagulable tissue factor without consequential increase in counter-regulatory pathways such as AT-III, activated protein C and plasminogen activator type 1. Lastly, influx of CD4+ T-cells in cardiac vasculature results in an increased production of cytokines that stimulate smooth muscle cells to migrate into the intima and generate collagen and other fibrous products leading to advancement of fatty streaks to advanced atherosclerotic lesions. Direct myocardial damage and cytokine storm leading to destabilization of pre-existing plaques and accelerated formation of new plaques are the two instigating mechanisms for acute coronary syndromes in COVID-19.


Assuntos
Síndrome Coronariana Aguda/etiologia , Betacoronavirus , Infecções por Coronavirus/complicações , Modelos Cardiovasculares , Pandemias , Pneumonia Viral/complicações , Síndrome Coronariana Aguda/fisiopatologia , Linfócitos T CD4-Positivos/imunologia , Quimiocinas/fisiologia , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/metabolismo , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/fisiopatologia , Citocinas/fisiologia , Humanos , Imunidade Inata , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/fisiopatologia , Ativação Plaquetária , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Vasoconstrição , Viroses/complicações , Viroses/imunologia
4.
PLoS One ; 15(8): e0238112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857805

RESUMO

This longitudinal study was performed to evaluate the feasibility of detecting the interaction between wall shear stress (WSS) and plaque development. 20 ApoE-/- mice were separated in 12 mice with Western Diet and 8 mice with Chow Diet. Magnetic resonance (MR) scans at 17.6 Tesla and histological analysis were performed after one week, eight and twelve weeks. All in vivo MR measurements were acquired using a flow sensitive phase contrast method for determining vectorial flow. Histological sections were stained with Hematoxylin and Eosin, Elastica van Gieson and CD68 staining. Data analysis was performed using Ensight and a Matlab-based "Flow Tool". The body weight of ApoE-/- mice increased significantly over 12 weeks. WSS values increased in the Western Diet group over the time period; in contrast, in the Chow Diet group the values decreased from the first to the second measurement point. Western Diet mice showed small plaque formations with elastin fragmentations after 8 weeks and big plaque formations after 12 weeks; Chow Diet mice showed a few elastin fragmentations after 8 weeks and small plaque formations after 12 weeks. Favored by high-fat diet, plaque formation results in higher values of WSS. With wall shear stress being a known predictor for atherosclerotic plaque development, ultra highfield MRI can serve as a tool for studying the causes and beginnings of atherosclerosis.


Assuntos
Aorta/diagnóstico por imagem , Imagem por Ressonância Magnética , Placa Aterosclerótica/diagnóstico por imagem , Animais , Aorta/patologia , Aorta/fisiopatologia , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Peso Corporal , Dieta Ocidental , Modelos Animais de Doenças , Estudos de Viabilidade , Feminino , Estudos Longitudinais , Imagem por Ressonância Magnética/instrumentação , Imagem por Ressonância Magnética/métodos , Camundongos Knockout , Placa Aterosclerótica/patologia , Placa Aterosclerótica/fisiopatologia , Distribuição Aleatória , Fluxo Sanguíneo Regional , Estresse Mecânico
5.
Clin Interv Aging ; 15: 853-863, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606625

RESUMO

Purpose: There have been few recent studies regarding vascular aging and its relationship with left ventricular (LV) geometry. Moreover, the association of abnormal LV geometry with various kinds of vascular aging has not yet been systematically analyzed. Thus, this study aimed to further elucidate this relationship. Materials and Methods: In this study, 3363 older participants (43.6% male, aged 71.1±5.9 years; 56.4% female, aged 71.1±6.1 years) derived from the Northern Shanghai Study were enrolled. Vascular aging criteria included arteriosclerosis, defined as carotid-femoral pulse wave velocity >10 m/s or brachial-ankle pulse wave velocity >1800 cm/s, and peripheral atherosclerosis, defined as ankle-brachial index <0.9, carotid artery intima-media thickness (cIMT) greater than 0.9 mm, or carotid plaque indicating carotid artery abnormality. Micro-albuminuria was defined as urinary albumin-to-creatinine ratio >30 mg/g. Decreased estimated glomerular filtration rate (eGFR) was defined as eGFR <60 mL/min/1.73 m2. Results: When vascular aging parameters were respectively adjusted for age and sex, arteriosclerosis, micro-albuminuria, and peripheral atherosclerosis were significantly associated with concentric remodeling, eccentric LV hypertrophy (LVH), and concentric LVH (P<0.045) but not with decreased eGFR or abnormal cIMT and presence of plaque. Peripheral atherosclerosis was strongly associated with LV concentric geometry (LVCG) when considering other covariates (risk factors, diseases, and treatments) (P<0.012). Conclusion: Vascular aging parameters such as arteriosclerosis, micro-albuminuria, and peripheral atherosclerosis are significantly and independently associated with LVCG in community-dwelling older Chinese population, suggesting the importance of vascular aging during early clinical assessment of abnormal LV geometry change and serious cardiovascular events.


Assuntos
Espessura Intima-Media Carotídea/normas , Hipertensão/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Remodelação Ventricular/fisiologia , Idoso , Índice Tornozelo-Braço , Artérias Carótidas/fisiopatologia , China/epidemiologia , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Vida Independente , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/fisiopatologia , Estudos Prospectivos , Análise de Onda de Pulso , Fatores de Risco
6.
Korean J Radiol ; 21(7): 900-907, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32524790

RESUMO

OBJECTIVE: To investigate the predictive value of intraplaque neovascularization (IPN) for cardiovascular outcomes. MATERIALS AND METHODS: We evaluated 217 patients with coronary artery disease (CAD) (158 men; mean age, 68 ± 10 years) with a maximal carotid plaque thickness ≥ 1.5 mm for the presence of IPN using contrast-enhanced ultrasonography. We compared patients with (n = 116) and without (n = 101) IPN during the follow-up period and investigated the predictors of major adverse cardiovascular events (MACE), including cardiac death, myocardial infarction, coronary artery revascularization, and transient ischemic accident/stroke. RESULTS: During the mean follow-up period of 995 ± 610 days, the MACE rate was 6% (13/217). Patients with IPN had a higher maximal thickness than those without IPN (2.86 ± 1.01 vs. 2.61 ± 0.84 mm, p = 0.046). Common carotid artery-peak systolic velocity, left ventricular mass index (LVMI), and ventricular-vascular coupling index were significantly correlated with MACE. However, on multivariate Cox regression analysis, increased LVMI was independently related to MACE (p < 0.05). The presence of IPN could not predict MACE. CONCLUSION: The presence of IPN was related to a higher plaque thickness but could not predict cardiovascular outcomes better than conventional clinical factors in patients with CAD.


Assuntos
Doença da Artéria Coronariana/terapia , Revascularização Miocárdica , Placa Aterosclerótica/fisiopatologia , Fatores Etários , Idoso , Artérias Carótidas/diagnóstico por imagem , Meios de Contraste/química , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/patologia , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Ultrassonografia
7.
Curr Atheroscler Rep ; 22(5): 19, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32458165

RESUMO

PURPOSE OF REVIEW: In this review, we discuss the evidence supporting the effects of statins on mast cells (MCs) in atherosclerosis and their molecular mechanism of action. RECENT FINDINGS: Statins or HMG-CoA reductase inhibitors are known for their lipid-lowering properties and are widely used in the prevention and treatment of cardiovascular diseases. There is growing evidence that statins have an inhibitory effect on MCs, which contributes to the pleiotropic effect of statins in various diseases. MCs are one of the crucial effectors of the immune system which play an essential role in the pathogenesis of multiple disorders. Recent studies have shown that MCs are involved in the development of atherosclerotic plaques. MCs secrete various inflammatory cytokines (IL-6, IL4, TNF-α, and IFNγ) and inflammatory mediators (histamine, tryptase, proteoglycans) after activation by various stimulants. This, in turn, will exacerbate atherosclerosis. Statins suppress the activation of MCs via IgE inhibition which leads to inhibition of inflammatory mediators and cytokines which are involved in the development and progression of atherosclerosis. In keeping with this evidence presented here, MCs can be considered as one of the therapeutic targets for statins in the treatment of atherosclerosis.


Assuntos
Aterosclerose/tratamento farmacológico , Aterosclerose/fisiopatologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Mastócitos/efeitos dos fármacos , Animais , Degranulação Celular/efeitos dos fármacos , Citocinas/metabolismo , Liberação de Histamina/efeitos dos fármacos , Humanos , Mastócitos/imunologia , Mastócitos/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Inibidores de Metaloproteinases de Matriz/uso terapêutico , Inibidores de Fosfolipase A2/farmacologia , Inibidores de Fosfolipase A2/uso terapêutico , Placa Aterosclerótica/fisiopatologia , Receptores de LDL/agonistas , Receptores Toll-Like/antagonistas & inibidores , Receptores Toll-Like/metabolismo
8.
Medicine (Baltimore) ; 99(17): e19911, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332671

RESUMO

Marathon runners demonstrate a high incidence of coronary artery plaque; however, studies on runners with exercise-induced hypertension (EIH) are sparse. We aimed to investigate the prevalence of coronary artery plaque among marathon runners with EIH.Veteran male marathon runners (≥40 and <60 years) underwent an exercise stress test. They were divided into 2 groups: normal blood pressure group (NBPG, n = 22), with resting systolic blood pressure (SBP)/diastolic blood pressure <140/90 mm Hg and maximal exercise SBP <210 mm Hg, and EIH group (EIHG, n = 28), with resting blood pressure <140/90 mm Hg and maximal exercise SBP ≥210 mm Hg. Coronary artery plaque and stenosis were compared using multi-detector computed tomography.The proportion of subjects with a coronary artery calcium (CAC) score ≥10 or ≥100 units, 1 or ≥2 plaques, or plaques in ≥2 blood vessels was higher in the EIHG than in the normal blood pressure group (NBPG) (P<.05). The absolute CAC score was higher in the EIHG (42.6 ±â€Š67.8) than in the NBPG (2.8 ±â€Š6.0; P < .05). The CAC score distribution was higher in the EIHG (5-300 units) than in the NBPG (P < .05). The prevalence of coronary plaques and maximal luminal artery stenosis was higher in the EIHG than in the NBPG (P < .05). The EIHG showed 12 cases of stenosis, whereas the NBPG showed only 1 case (P < .05).In marathon runners, EIH was associated with increased prevalence of coronary artery plaques and could be a new risk factor for coronary artery plaque formation. Therefore, preventive measures and EIH monitoring using an exercise stress test, alongside multi-detector computed tomography, are recommended.


Assuntos
Doença da Artéria Coronariana/complicações , Exercício Físico/fisiologia , Hipertensão/etiologia , Prevalência , Corrida/fisiologia , Adulto , Atletas , Doença da Artéria Coronariana/fisiopatologia , Teste de Esforço/métodos , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/fisiopatologia , Fatores de Risco , Estatísticas não Paramétricas , Tomografia Computadorizada por Raios X/métodos
9.
Clin Exp Hypertens ; 42(7): 608-613, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-32316781

RESUMO

INTRODUCTION: Visit-to-visit variability (VVV) in blood pressure (BP) has been reported to be a strong predictor of cardiovascular disease. However, the association between VVV in BP and coronary plaque composition has not been fully elucidated. METHODS: One hundred-two consecutive patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) using integrated backscatter (IB) intravascular ultrasound (IVUS), and who had at least six clinic visits a year before PCI were included. We measured systolic and diastolic BP (SBP and DBP) at each visit and determined VVV in BP expressed as the standard deviation of the average BP. Grayscale and IB IVUS examinations were performed for the culprit lesion of a coronary artery just before PCI. RESULTS: There were no significant associations between the average SBP or DBP and various IVUS parameters. However, VVV in SBP was positively correlated with both the percentage (%) of atheroma volume (ß = 0.23, p = .02) and % lipid volume (ß = 0.53, p < .0001). VVV in DBP was positively correlated with % lipid volume (ß = 0.24, p = .01), while there was no significant correlation between VVV in DBP and % atheroma volume. A  multivariable linear regression analysis showed that VVV in SBP was independently associated with % atheroma volume (p = .04) and % lipid volume (p < .001). CONCLUSIONS: Larger VVV in SBP was significantly associated with an increased plaque burden and lipid composition at the culprit lesion of a coronary artery in CAD patients. The improvement of VVV in SBP may contribute to the regression and stabilization of coronary plaques.


Assuntos
Pressão Sanguínea , Doença da Artéria Coronariana/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/cirurgia , Diástole , Feminino , Humanos , Lipídeos , Masculino , Pessoa de Meia-Idade , Visita a Consultório Médico , Intervenção Coronária Percutânea , Placa Aterosclerótica/fisiopatologia , Sístole , Ultrassonografia de Intervenção
10.
Circ Cardiovasc Imaging ; 13(3): e009539, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32164454

RESUMO

BACKGROUND: Inflammation and microcalcification are interrelated processes contributing to atherosclerotic plaque vulnerability. Positron-emission tomography can quantify these processes in vivo. This study investigates (1) 18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) uptake in culprit versus nonculprit carotid atheroma, (2) spatial distributions of uptake, and (3) how macrocalcification affects this relationship. METHODS: Individuals with acute ischemic stroke with ipsilateral carotid stenosis of ≥50% underwent FDG-positron-emission tomography and NaF-positron-emission tomography. Tracer uptake was quantified using maximum tissue-to-background ratios (TBRmax) and macrocalcification quantified using Agatston scoring. RESULTS: In 26 individuals, median most diseased segment TBRmax (interquartile range) was higher in culprit than in nonculprit atheroma for both FDG (2.08 [0.52] versus 1.89 [0.40]; P<0.001) and NaF (2.68 [0.63] versus 2.39 [1.02]; P<0.001). However, whole vessel TBRmax was higher in culprit arteries for FDG (1.92 [0.41] versus 1.71 [0.31]; P<0.001) but not NaF (1.85 [0.28] versus 1.79 [0.60]; P=0.10). NaF uptake was concentrated at carotid bifurcations, while FDG was distributed evenly throughout arteries. Correlations between FDG and NaF TBRmax differed between bifurcations with low macrocalcification (rs=0.38; P<0.001) versus high macrocalcification (rs=0.59; P<0.001). CONCLUSIONS: This is the first study to demonstrate increased uptake of both FDG and NaF in culprit carotid plaques, with discrete distributions of pathophysiology influencing vulnerability in vivo. These findings have implications for our understanding of the natural history of the disease and for the clinical assessment and management of carotid atherosclerosis.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Isquemia Encefálica/etiologia , Artérias Carótidas/diagnóstico por imagem , Estenose das Carótidas/diagnóstico , Placa Aterosclerótica/diagnóstico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Isquemia Encefálica/diagnóstico , Estenose das Carótidas/complicações , Estenose das Carótidas/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Placa Aterosclerótica/complicações , Placa Aterosclerótica/fisiopatologia , Estudos Prospectivos
11.
Obesity (Silver Spring) ; 28(4): 749-755, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32086864

RESUMO

OBJECTIVE: People with HIV (PWH) who are well treated on antiretroviral therapy remain at increased risk for body composition changes, including increased visceral adipose tissue (VAT) and reduced subcutaneous adipose tissue (SAT), as well as increased cardiovascular disease (CVD). The relationship between adipose compartments and coronary disease is not well understood among PWH. METHODS: A total of 148 PWH and 68 uninfected individuals without CVD were well phenotyped for VAT and SAT via single-section abdominal computed tomography (CT) at L4. Coronary artery calcium (CAC) score was assessed by noncontrast cardiac CT and coronary plaque composition by coronary CT angiography. RESULTS: Increased VAT was significantly related to increased presence of plaque (OR, 1.55 per 100 cm2 ; P = 0.008) and CAC > 0 (OR, 1.56 per 100 cm2 ; P = 0.006) in the HIV group. In contrast, increased SAT was related to reduced presence of plaque (OR, 0.79 per 100 cm2 ; P = 0.057) and reduced CAC > 0 (OR, 0.69 per 100 cm2 , P = 0.007) among PWH. The VAT to SAT ratio showed a strong relationship to overall presence of calcified plaque (OR, 3.30; P = 0.03) and CAC > 0 (OR, 3.57; P < 0.001) in the HIV group. VAT and waist to hip ratio, but not SAT, were strong predictors of plaque in the uninfected group. BMI did not relate in either group. CONCLUSIONS: Fat redistribution phenotyping by simultaneous quantification of VAT and SAT as independent measures could help identify those PWH at higher risk for CVD.


Assuntos
Tecido Adiposo/fisiopatologia , Doença da Artéria Coronariana/etiologia , Infecções por HIV/complicações , Placa Aterosclerótica/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Eur J Radiol ; 125: 108874, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32087467

RESUMO

PURPOSE: South Asian (SA) have been observed to have higher cardiovascular mortality rates compared to East Asians (EA) and Caucasians. Pericoronary adipose tissue (PCAT) attenuation around the right coronary artery (RCA) from coronary CT angiography (CTA) has been associated with coronary inflammation and cardiac death. We aimed to investigate i) the relationship between plaque characteristics and PCAT attenuation and ii) to assess gender and ethnic differences in PCAT attenuation using a matched cohort of SA, EA and Caucasians. METHOD: Three-hundred symptomatic patients who underwent CTA were matched for age, gender, BMI and diabetes (100 in each ethnic group). Semi-automated software was used to quantify the total volumes and burden of non-calcified plaque (NCP), low-density non-calcified plaque (LD-NCP) and calcified plaque (CP) in blinded core-lab analysis. PCAT CT attenuation was measured around the RCA (10-50 mm from RCA ostium), the most standardized model for PCAT analysis. RESULTS: The total volumes and burden of NCP, LD-NCP and CP were comparable in the ethnic groups (each p > 0.05). PCAT attenuation was higher in patients with coronary plaque. PCAT attenuation correlated with the total volumes and burden of NCP, LD-NCP and CP (r>0.17; p < 0.003). Within the RCA this correlation persisted only for NCP features (r>0.39;p < 0.001). Males showed higher PCAT attenuation (p < 0.001). PCAT attenuation was similar between Caucasian, EA and SA (p = 0.32). CONCLUSIONS: PCAT CT attenuation correlated most with its surrounded NCP features further highlighting its role as surrogate measure of coronary inflammation. As coronary plaque burden and RCA PCAT attenuation did not differ between ethnic groups, causes of increased cardiac mortality in South Asians needs further investigations.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Dor no Peito/fisiopatologia , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Placa Aterosclerótica/diagnóstico por imagem , Tecido Adiposo/fisiopatologia , Ásia , Estudos de Coortes , Europa (Continente) , Estudos de Avaliação como Assunto , Extremo Oriente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/fisiopatologia , Índice de Gravidade de Doença , Fatores Sexuais
13.
Stroke ; 51(3): 938-943, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31893985

RESUMO

Background and Purpose- Atrial cardiopathy and atherosclerotic plaque are two potential mechanisms underlying embolic strokes of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. A better understanding of their association may inform targeted secondary prevention strategies. Methods- We examined the association between atrial cardiopathy and atherosclerotic plaque in the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), which enrolled 7213 patients with recent ESUS during 2014 to 2017. For this analysis, we included patients with data on left atrial dimension, location of brain infarction, and cervical large artery plaque. The variables of primary interest were left atrial diameter and cervical plaque ipsilateral to brain infarction. Secondary markers of atrial cardiopathy were premature atrial contractions on Holter monitoring and newly diagnosed atrial fibrillation. For descriptive purposes, left atrial enlargement was defined as ≥4.7 cm. Multivariable logistic regression was used to examine the association between atrial cardiopathy markers and ipsilateral plaque after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, current smoking, and hyperlipidemia. Results- Among 3983 eligible patients, 235 (5.9%) had left atrial enlargement, 939 (23.6%) had ipsilateral plaque, and 94 (2.4%) had both. Shared risk factors for left atrial enlargement and ipsilateral plaque were male sex, white race, hypertension, tobacco use, and coronary artery disease. Despite shared risk factors, increasing left atrial dimension was not associated with ipsilateral plaque after adjustment for covariates (odds ratio per cm, 1.1 [95% CI, 1.0-1.2]; P=0.08). We found no consistent associations between secondary markers of atrial cardiopathy and ipsilateral plaque. Conclusions- In a large population of patients with ESUS, we did not observe a notable association between atrial cardiopathy and atherosclerotic plaque, and few patients had both conditions. These findings suggest that atrial cardiopathy and atherosclerotic plaque may be distinct, nonoverlapping risk factors for stroke among ESUS patients.


Assuntos
Infarto Encefálico , Cardiomegalia , Embolia Intracraniana , Placa Aterosclerótica , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral , Idoso , Biomarcadores/sangue , Infarto Encefálico/sangue , Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/fisiopatologia , Cardiomegalia/sangue , Cardiomegalia/tratamento farmacológico , Cardiomegalia/fisiopatologia , Feminino , Átrios do Coração/fisiopatologia , Humanos , Embolia Intracraniana/sangue , Embolia Intracraniana/tratamento farmacológico , Embolia Intracraniana/fisiopatologia , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/fisiopatologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia
14.
Stroke ; 51(3): 838-845, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31948355

RESUMO

Background and Purpose- In randomized trials of symptomatic carotid endarterectomy, only modest benefit occurred in patients with moderate stenosis and important subgroups experienced no benefit. Carotid plaque 18F-fluorodeoxyglucose uptake on positron emission tomography, reflecting inflammation, independently predicts recurrent stroke. We investigated if a risk score combining stenosis and plaque 18F-fluorodeoxyglucose would improve the identification of early recurrent stroke. Methods- We derived the score in a prospective cohort study of recent (<30 days) non-severe (modified Rankin Scale score ≤3) stroke/transient ischemic attack. We derived the SCAIL (symptomatic carotid atheroma inflammation lumen-stenosis) score (range, 0-5) including 18F-fluorodeoxyglucose standardized uptake values (SUVmax <2 g/mL, 0 points; SUVmax 2-2.99 g/mL, 1 point; SUVmax 3-3.99 g/mL, 2 points; SUVmax ≥4 g/mL, 3 points) and stenosis (<50%, 0 points; 50%-69%, 1 point; ≥70%, 2 points). We validated the score in an independent pooled cohort of 2 studies. In the pooled cohorts, we investigated the SCAIL score to discriminate recurrent stroke after the index stroke/transient ischemic attack, after positron emission tomography-imaging, and in mild or moderate stenosis. Results- In the derivation cohort (109 patients), recurrent stroke risk increased with increasing SCAIL score (P=0.002, C statistic 0.71 [95% CI, 0.56-0.86]). The adjusted (age, sex, smoking, hypertension, diabetes mellitus, antiplatelets, and statins) hazard ratio per 1-point SCAIL increase was 2.4 (95% CI, 1.2-4.5, P=0.01). Findings were confirmed in the validation cohort (87 patients, adjusted hazard ratio, 2.9 [95% CI, 1.9-5], P<0.001; C statistic 0.77 [95% CI, 0.67-0.87]). The SCAIL score independently predicted recurrent stroke after positron emission tomography-imaging (adjusted hazard ratio, 4.52 [95% CI, 1.58-12.93], P=0.005). Compared with stenosis severity (C statistic, 0.63 [95% CI, 0.46-0.80]), prediction of post-positron emission tomography stroke recurrence was improved with the SCAIL score (C statistic, 0.82 [95% CI, 0.66-0.97], P=0.04). Findings were confirmed in mild or moderate stenosis (adjusted hazard ratio, 2.74 [95% CI, 1.39-5.39], P=0.004). Conclusions- The SCAIL score improved the identification of early recurrent stroke. Randomized trials are needed to test if a combined stenosis-inflammation strategy improves selection for carotid revascularization where benefit is currently uncertain.


Assuntos
Estenose das Carótidas , Placa Aterosclerótica , Tomografia por Emissão de Pósitrons , Acidente Vascular Cerebral , Idoso , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/fisiopatologia , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/fisiopatologia , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia
15.
Eur Radiol ; 30(4): 2403-2411, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31900697

RESUMO

OBJECTIVES: The objective of this study was to evaluate whether baseline 18F-fluorodeoxyglucose (FDG) uptake is associated with carotid plaque progression. METHODS: A total of 156 subjects with carotid plaque were enrolled and underwent carotid magnetic resonance imaging (MRI) (at baseline and the 12-month follow-up) and positron emission tomography-computed tomography (PET-CT) (baseline). Carotid plaque progression was evaluated by two indices (the incidence of plaque progression and percentage of plaque increase) with three-dimensional (3D) imaging, while the 18F-FDG uptake was evaluated by the 18F-FDG uptake levels and 18F-FDG uptake velocity. The association between plaque progression and 18F-FDG uptake was investigated by the trend test and multivariate logistic regression analysis. RESULTS: Of the 156 subjects, 80 (51.3%) showed carotid plaque progression during the 12-month follow-up. Firstly, no association was found between 18F-FDG uptake levels and plaque progression. Secondly, significant differences in the incidence of plaque progression were observed among the groups with different uptake velocities, showing a significant decreasing trend ranging from high to intermediate to low (p = 0.002, trend test). After adjusting for covariates, an adequate prediction of the 18F-FDG uptake velocity for the incidence of plaque progression was revealed (OR = 0.682, p < 0.05). In addition, no association was found between the 18F-FDG uptake velocity and the percentage of plaque increase in the subjects with plaque progression (p = 0.757, trend test). CONCLUSIONS: Our findings suggest 18F-FDG uptake velocity is independently associated with the incidence of carotid plaque progression. Additionally, the 18F-FDG uptake velocity, as another important parameter of PET-CT, warrants further study in future clinical research. KEY POINTS: • The18F-FDG uptake levels were not associated with the carotid plaque progression. • The18F-FDG uptake velocity could predict the incidence of carotid plaque progression. • The18F-FDG uptake velocity with related factors warrants more attention in future clinical research.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Doenças das Artérias Carótidas/diagnóstico , Fluordesoxiglucose F18/farmacologia , Imagem por Ressonância Magnética/métodos , Placa Aterosclerótica/diagnóstico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Doenças das Artérias Carótidas/fisiopatologia , Progressão da Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/fisiopatologia , Compostos Radiofarmacêuticos/farmacologia
16.
Eur J Radiol ; 122: 108744, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31790934

RESUMO

PURPOSE: The study aimed to compare morphological and anatomic plaque markers derived from coronary computed tomography angiography (cCTA) for the detection of lesion specific ischemia with invasive instantaneous wave free ratio (iFR®) as the reference standard. METHODS: In our prospective study, we enrolled patients with suspected coronary artery disease (CAD), who had undergone cCTA, using a low-dose third-generation dual-source CT and invasive coronary angiography (ICA) with iFR® measurement. Various plaque markers were assessed on cCTA. Discriminatory power of these markers for the detection of ischemia-inducing coronary artery disease was evaluated against invasive iFR®. RESULTS: Our study cohort included 39 patients (66.6 ± 12.0 years, 72 % male). Among 54 vessel-specific lesions, 15 lesions (28 %) were characterized as hemodynamically significant by iFR® ≤0.89. The area under the curve (AUC) of lesion length/ minimal luminal diameter4 (LL/MLD4) (0.84) was greater than the AUC of minimal luminal area (MLA) (0.82), MLD (0.81), the degree of luminal diameter stenosis (0.81), corrected coronary opacification (CCO) (0.79), remodeling index (RI) (0.75), and percentage aggregate plaque volume (%APV) (0.72). LL, vessel volume (VV), total plaque volume (TPV), calcified and non-calcified plaque volume (CPV and NCPV) did not reach statistical significance and were unable to discriminate between vessels with and without ischemia-inducing coronary stenosis. CONCLUSION: LL/MLD4, MLA, MLD, the degree of luminal diameter stenosis, CCO, RI, and %APV derived from cCTA can support the detection of hemodynamically significant coronary stenosis as compared with iFR®, with LL/MLD4 showing the greatest discriminatory power.


Assuntos
Estenose Coronária/diagnóstico por imagem , Hemodinâmica/fisiologia , Placa Aterosclerótica/diagnóstico por imagem , Idoso , Área Sob a Curva , Biomarcadores/metabolismo , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Estenose Coronária/fisiopatologia , Feminino , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/fisiopatologia , Estudos Prospectivos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
17.
Stroke ; 51(1): 311-314, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31752616

RESUMO

Background and Purpose- An ipsilateral mild carotid stenosis, defined as plaque with <50% luminal narrowing, is identified in nearly 40% of patients with embolic stroke of undetermined source and could represent an unrecognized source of atheroembolism. We aimed to summarize data about the frequency of mild carotid stenosis with high-risk features in embolic stroke of undetermined source. Methods- We searched Pubmed and Ovid-Embase for studies reporting carotid plaque imaging features in embolic stroke of undetermined source. The prevalence of ipsilateral and contralateral mild carotid stenosis with high-risk features was pooled using random-effect meta-analysis. Results- Eight studies enrolling 323 participants were included. The prevalence of mild carotid stenosis with high-risk features in the ipsilateral carotid was 32.5% (95% CI, 25.3-40.2) compared with 4.6% (95% CI, 0.1-13.1) in the contralateral carotid. The odds ratio of finding a plaque with high-risk features in the ipsilateral versus the contralateral carotid was 5.5 (95% CI, 2.5-12.0). Conclusions- Plaques with high-risk features are 5 times more prevalent in the ipsilateral compared with the contralateral carotid in embolic stroke of undetermined source, suggesting a relationship to stroke risk.


Assuntos
Estenose das Carótidas , Embolia Intracraniana , Placa Aterosclerótica , Idoso , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/fisiopatologia , Feminino , Humanos , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/etiologia , Embolia Intracraniana/fisiopatologia , Masculino , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/fisiopatologia , Fatores de Risco , Ultrassonografia
18.
Nucl Med Commun ; 41(2): 126-132, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31860524

RESUMO

OBJECTIVES: Atherosclerotic plaque molecular imaging with F-sodium fluoride (NaF) PET with computed tomography (PET-CT) may identify active unstable microcalcification. We sought to explore renal arteries calcification activity in a group of high cardiovascular (CV) risk subjects without manifest CV disease. METHODS: High CV risk hypertensive individuals from a single centre were prospectively scanned with F-NaF-PET-CT in major vascular territories. Renal arterial wall activity was retrospectively analysed and expressed as the ratio between maximum standard uptake value in the lesion and mean blood pool activity in the superior vena cava [tissue-to-background ratio (TBR)]. We explored renal artery wall F-NaF activity's association to CV risk factors and renal function. RESULTS: Mean age was 64 ± 8.6 years, 56% male, 96% Caucasian and 24% had chronic kidney disease (CKD) (n = 25). Six individuals (24%) showed renal artery wall radiotracer uptake (TBR 1.4 ± 0.4); these subjects were heavier, had higher triglycerides, high-sensitivity C-reactive protein and predicted CV risk (SCORE) compared to the remaining cohort (P < 0.05 for all comparisons). There was a trend toward higher F-NaF uptake in other major vessels and increased thoracic fat volume in subjects with renal artery wall uptake. Glomerular filtration rate (GFR) was lower in subjects with positive renal plaques (93.0 ± 29.7 vs. 65.0 ± 19.7 ml/min, P = 0.04). Renal artery radiotracer uptake and eGFR were inversely correlated (r = -0.42, P = 0.04). CONCLUSION: In a high CV risk group without manifest CV disease, higher renal artery wall F-NaF activity is associated with superior predicted CV risk and lower GFR.


Assuntos
Radioisótopos de Flúor , Taxa de Filtração Glomerular , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/fisiopatologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Artéria Renal/diagnóstico por imagem , Fluoreto de Sódio , Idoso , Calcinose/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/complicações , Estudos Retrospectivos , Fatores de Risco
19.
Cardiol Rev ; 28(1): 3-9, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30489331

RESUMO

Advances in our understanding of the natural history and biology of atherosclerotic vascular disease led to the concept of a vulnerable plaque (VP), which is predisposed toward more rapid progression and acute coronary events. With newer technologies, we now have at our disposal high-quality imaging studies, both invasive and noninvasive, which promise in identifying plaque characteristics that make it more vulnerable. Upcoming trials aim to evaluate the utility of imaging VP in predicting clinical events. We discuss the role of VP imaging in managing atherosclerotic vascular disease.


Assuntos
Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/fisiopatologia , Humanos
20.
Cells ; 9(1)2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31878229

RESUMO

Atherosclerosis and associated ischemic organ dysfunction represent the number one cause of mortality worldwide. While the key drivers of atherosclerosis, arterial hypertension, hypercholesterolemia and diabetes mellitus, are well known disease entities and their contribution to the formation of atherosclerotic plaques are intensively studied and well understood, less effort is put on the effect of these disease states on microvascular structure an integrity. In this review we summarize the pathological changes occurring in the vascular system in response to prolonged exposure to these major risk factors, with a particular focus on the differences between these pathological alterations of the vessel wall in larger arteries as compared to the microcirculation. Furthermore, we intend to highlight potential therapeutic strategies to improve microvascular function during atherosclerotic vessel disease.


Assuntos
Aterosclerose/fisiopatologia , Capilares/metabolismo , Microvasos/metabolismo , Artérias/patologia , Aterosclerose/sangue , Capilares/fisiologia , Diabetes Mellitus , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos , Hipercolesterolemia , Hipertensão , Microvasos/fisiologia , Placa Aterosclerótica/fisiopatologia
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