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OBJECTIVES: As a novel imaging marker, pericoronary fat attenuation index (FAI) reflects the local coronary inflammation which is one of the major mechanisms for in-stent restenosis (ISR). We aimed to validate the ability of pericoronary FAI to predict ISR in patients undergoing percutaneous coronary intervention (PCI). MATERIALS AND METHODS: Patients who underwent coronary CT angiography (CCTA) before PCI within 1 week between January 2017 and December 2019 at our hospital and had follow-up invasive coronary angiography (ICA) or CCTA were enrolled. Pericoronary FAI was measured at the site where stents would be placed. ISR was defined as ≥ 50% diameter stenosis at follow-up ICA or CCTA in the in-stent area. Multivariable analysis using mixed effects logistic regression models was performed to test the association between pericoronary FAI and ISR at lesion level. RESULTS: A total of 126 patients with 180 target lesions were included in the study. During 22.5 months of mean interval time from index PCI to follow-up ICA or CCTA, ISR occurred in 40 (22.2%, 40/180) stents. Pericoronary FAI was associated with a higher risk of ISR (adjusted OR = 1.12, p = 0.028). The optimum cutoff was - 69.6 HU. Integrating the dichotomous pericoronary FAI into current state of the art prediction model for ISR improved the prediction ability of the model significantly (â³area under the curve = + 0.064; p = 0.001). CONCLUSION: Pericoronary FAI around lesions with subsequent stent placement is independently associated with ISR and could improve the ability of current prediction model for ISR. CLINICAL RELEVANCE STATEMENT: Pericoronary fat attenuation index can be used to identify the lesions with high risk for in-stent restenosis. These lesions may benefit from extra anti-inflammation treatment to avoid in-stent restenosis. KEY POINTS: ⢠Pericoronary fat attenuation index reflects the local coronary inflammation. ⢠Pericoronary fat attenuation index around lesions with subsequent stents placement can predict in-stent restenosis. ⢠Pericoronary fat attenuation index can be used as a marker for future in-stent restenosis.
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Angiografía por Tomografía Computarizada , Angiografía Coronaria , Reestenosis Coronaria , Intervención Coronaria Percutánea , Valor Predictivo de las Pruebas , Stents , Humanos , Masculino , Femenino , Reestenosis Coronaria/diagnóstico por imagen , Reestenosis Coronaria/etiología , Persona de Mediana Edad , Intervención Coronaria Percutánea/métodos , Stents/efectos adversos , Angiografía por Tomografía Computarizada/métodos , Anciano , Tejido Adiposo/diagnóstico por imagen , Estudios Retrospectivos , Tejido Adiposo EpicárdicoRESUMEN
Background Lipid-rich plaques detected with intravascular imaging are associated with adverse cardiovascular events in patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS). But evidence about the prognostic implication of coronary CT angiography (CCTA) in NSTE ACS is limited. Purpose To assess whether quantitative variables at CCTA that reflect lipid content in nonrevascularized plaques in individuals with NSTE ACS might be predictors of subsequent nonrevascularized plaque-related major adverse cardiovascular events (MACEs). Materials and Methods In this multicenter prospective cohort study, from November 2017 to January 2019, individuals diagnosed with NSTE ACS (excluding those at very high risk) were enrolled and underwent CCTA before invasive coronary angiography (ICA) within 1 day. Lipid core was defined as areas with attenuation less than 30 HU in plaques. MACEs were defined as cardiac death, myocardial infarction, hospitalization for unstable angina, and revascularization. Participants were followed up at 6 months, 12 months, and annually thereafter for at least 3 years (ending by July 2022). Multivariable analysis using Cox proportional hazards regression models was performed to determine the association between lipid core burden, lipid core volume, and future nonrevascularized plaque-related MACEs at both the participant and plaque levels. Results A total of 342 participants (mean age, 57.9 years ± 11.1 [SD]; 263 male) were included for analysis with a median follow-up period of 4.0 years (IQR, 3.6-4.4 years). The 4-year nonrevascularized plaque-related MACE rate was 23.9% (95% CI: 19.1, 28.5). Lipid core burden (hazard ratio [HR], 12.6; 95% CI: 4.6, 34.3) was an independent predictor at the participant level, with an optimum threshold of 2.8%. Lipid core burden (HR, 12.1; 95% CI: 6.6, 22.3) and volume (HR, 11.0; 95% CI: 6.5, 18.4) were independent predictors at the plaque level, with an optimum threshold of 7.2% and 10.1 mm3, respectively. Conclusion In NSTE ACS, quantitative analysis of plaque lipid content at CCTA independently predicted participants and plaques at higher risk for future nonrevascularized plaque-related MACEs. Chinese Clinical Trial Registry no. ChiCTR1800018661 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Tavakoli and Duman in this issue.
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Síndrome Coronario Agudo , Angiografía por Tomografía Computarizada , Humanos , Masculino , Persona de Mediana Edad , Síndrome Coronario Agudo/diagnóstico por imagen , Angiografía Coronaria , Estudios Prospectivos , LípidosRESUMEN
OBJECTIVES: To explore whether radiomics-based machine learning (ML) models could outperform conventional diagnostic methods at identifying vulnerable lesions on coronary computed tomographic angiography (CCTA). METHODS: In this retrospective study, 36 heart transplant recipients with coronary heart disease (CAD) and end-stage heart failure were included. Pathological cross-section samples of 350 plaques were collected and coregistered to patients' preoperative CCTA images. A total of 1184 radiomic features were extracted from CCTA images. Through feature selection and stratified fivefold cross-validation, we derived eight radiomics-based ML models for lesion vulnerability prediction. An independent set of 196 plaques from another 8 CAD patients who underwent heart transplants was collected to validate radiomics-based ML models' diagnostic accuracy against conventional CCTA feature-based diagnosis (presence of at least 2 high-risk plaque features). The performance of the prediction models was assessed by the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals (CI). RESULTS: The training group used to develop radiomics-based ML models contained 200/350 (57.1%) vulnerable plaques and the external validation group was composed of 67.3% (132/196) vulnerable plaques. The radiomics-based ML model based on eight radiomic features showed excellent cross-validation diagnostic accuracy (AUC: 0.900 ± 0.033). In the validation group, diagnosis based on conventional CCTA features demonstrated moderate performance (AUC: 0.656 [95% CI: 0.593 -0.718]), while the radiomics-based ML model showed higher diagnostic ability (0.782 [95% CI: 0.710 -0.846]). CONCLUSIONS: Radiomics-based ML models showed better diagnostic ability than the conventional CCTA features at assessing coronary plaque vulnerability. KEY POINTS: ⢠CCTA has great potential in the diagnosis of vulnerable coronary artery lesions. ⢠Radiomics model built through CCTA could discriminate coronary vulnerable lesions in good diagnostic ability. ⢠Radiomics model could improve the ability of vulnerability diagnosis against traditional CCTA method, sensitivity especially.
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Aterosclerosis , Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Angiografía por Tomografía Computarizada/métodos , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Humanos , Placa Aterosclerótica/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
Background: For complicated Stanford type B aortic dissection (TBAD), thoracic endovascular aortic repair (TEVAR) is the recommended treatment; however, the type of renal artery that should be repaired remains controversial. The study aimed to investigate the changes in the renal artery and renal volume in complicated TBAD after TEVAR and the predictors of renal atrophy. Methods: The cohort study retrospectively enrolled patients with acute and subacute complicated TBAD who underwent aortic computed tomography angiography (CTA) 1 month before as well as 1 week and half a year after TEVAR from January 2010 to May 2017. According to the source of blood supply shown in preoperative CT, the renal artery was classified in 3 ways: type 1, supplied by the aortic true lumen; type 2, supplied by the aortic false lumen; or type 3, supplied by both the true and false lumen. Results: A total of 91 patients (81 men and 10 women) with an average age of 48.12±10.35 years were enrolled. Renal arteries were classified as type 1 (n=91), type 2 (n=35), and type 3 (n=56). There was no difference in the distribution of the 3 types on the left and right sides (type 1 vs. type 2 vs. type 3: 52:39 vs. 15:20 vs. 24:32; P=0.152). After TEVAR, type 3 was more likely to have spontaneous healing than type 2 (16.1% vs. 2.9%; P=0.049). There was no significant difference in the preoperative volume of kidneys of the 3 types (type 1 vs. type 2 vs. type 3: 198.23±38.68 vs. 197.37±41.77 vs. 195.10±36.11 mL; P=0.893). The postoperative volume of types 2 and 3 was smaller than that of type 1 (type 1 vs. type 2 vs. type 3: 190.09±43.25 vs. 165.15±52.63 vs. 170.70±45.28 mL; P=0.006). The renal volume was reduced in all 3 types of renal artery, especially in type 2 (the change of renal volume for type 1 vs. type 2 vs. type 3: -8.14±29.31 vs. -32.22±41.59 vs. -24.41±38.44 mL; P=0.001). The relative change of renal volume for type 1 vs. type 2 vs. type 3: (-3.64±15.69)% vs. (-16.00±21.29)% vs. (-11.97±18.22)%; P=0.001). During the median follow-up of 668 days, 7 patients (7.7%) belonging to types 2 and 3 developed renal atrophy. False lumen thrombosis in the abdominal aorta and/or the renal artery was the predictor of renal atrophy [hazard ratio (HR) =17.757; P=0.008]. Conclusions: Patients with type 2 or 3 renal artery and false lumen thrombosis in the abdominal aorta and/or renal artery should be monitored closely and actively intervened to prevent renal atrophy.
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Background: The napkin-ring sign (NRS) was accepted as unstable plaques at coronary computed tomography angiography (CCTA). However, the incidence is relatively low. We sought to assess whether the newly defined diamond-attenuation-sign [DAS, defined as a qualitative plaque feature in a mixed plaque (MP) on CCTA cross-section images by the presence of two features: a visual calcification (in the shape of a diamond) accompanied by an annular-shape lower attenuation plaque tissue surrounding the lumen like a ring], could be accurately identified as unstable atherosclerotic plaques. Methods: Eight heart transplant recipients (8 male; mean age, 48.5±11.6 years; range, 37-65 years) underwent CCTA exams prior to heart transplant surgery. Segment-based CCTA sections were independently evaluated for various plaque patterns including non-calcified plaque (NCP) with NRS (NCP-NRS), NCP without NRS (NCP-non-NRS), MP with DAS (MP-DAS), MP without DAS sign (MP-non-DAS), and calcified plaque (CP). Results: NCP-NRS plaques in 6.4% (23/358), NCP-non-NRS plaques in 24.0% (86/358), MP-DAS plaques in 18.2% (65/358), MP-non-DAS plaques in 20.1% (72/358), and calcified-plaques in 7.0% (25/358) of all cases. The specificity and positive predictive values of the MP-DAS and NCP-NRS signs to identify unstable plaque features were excellent (97.1% vs. 98.6%, 90.8% vs. 87.0%, respectively). DAS plaques were more frequently seen on CCTA exams than that of NRS (39.3% vs. 13.3%, respectively, P=0.001). The diagnostic performance of MP-DAS to identify unstable coronary lesions was superior compared to NCP-NRS [area under the receiver operating characteristic curve (ROC), 0.756; 95% CI: 0.717-0.791 vs. 0.558; 95% CI: 0.514-0.600, respectively, P<0.001]. Conclusions: Both the DAS and NRS had a high specificity and positive predictive value for the presence of unstable lesions. DAS was a better identification of unstable atherosclerotic plaques in the assessment of plaque-calcification-pattern (PCP).
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BACKGROUND: A limitation associated with coronary computed tomography angiography (CCTA) is the lack of a normal reference value for aortic root dimensions and the uncertainty of the influence of age and gender on these dimensions. The purpose of the present study was to identify the normal values and variations of aortic root dimensions in healthy individuals and investigate how gender and age affect aortic root size. METHODS: A total of 1286 healthy yellow population (52.7 ± 11.0 years, 634 male) who underwent CCTA were retrospectively included in the present study. Male and female patients were divided into seven groups according to age (< 30 years old, 30-39, 40-49, 50-59, 60-69, 70-79, ≥ 80 years old). In these age groups, we measured and compared the parameters of the aortic root. RESULTS: After body surface area (BSA) correction, the aortic root parameters of females were found to be greater than those of males in the 40-49 age group (P<0.05). There were no significant differences in aortic root parameters between genders in other age groups, except for the diameter of the ascending aorta, which was greater in females (P<0.05). In males, age was positively correlated with aortic root parameters (P<0.05), except for the annulus short diameter and LVOT short diameter. In females, age was positively correlated with aortic root parameters (P<0.05), except for the left coronary ostia height and the LVOT short diameter. CONCLUSION: Aortic root dimensions are affected by age and gender. After BSA correction, females show larger aortic root dimensions than males, and aortic root diameters increase with age.
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There is controversy about whether symptomatic population with coronary artery calcium score (CACS) of zero have coronary artery disease (CAD) and the distribution at different ages. We sought to analyze the prevalence of CAD in symptomatic patients with zero CACS, especially in different age groups. We studied patients suspected of CAD and underwent CACS scan and coronary computed tomography angiography (CTA). We included patients with CACS of zero. Clinical data was collected to achieve information on demographic characteristics and risk factors. The presence of plaque and obstructive CAD were analyzed based on coronary CTA. The association between age and the prevalence of plaque and obstructive CAD was evaluated.Overall 5514 patients (51.1% men; mean age 54.40 years) were analyzed, of whom 4120 (74.72%) with normal coronary artery, 1394 (25.28%) with plaque and 514 (9.32%) with obstructive CAD. The prevalence of plaque and obstructive CAD increased significantly with age (p < 0.001). Age was significantly associated with the risk of developing plaque and obstructive CAD in the unadjusted model and multivariate model. Taking age less than 40 as a reference, risk ratios (RRs) of prevalence of plaque increased with age in the multivariate model (RR = 2.353 for 40-50, RR = 6.489 for > 70). RRs of prevalence of obstructive CAD also increased with age in the multivariate model (RR = 2.075 for 40-50, RR = 4.102 for > 70). Quite a few CAD could occur in symptomatic patients with CACS of zero, especially in old patients. Coronary CTA was required to exclude CAD in this cohort.
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Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/epidemiología , Adulto , Distribución por Edad , Factores de Edad , Anciano , Beijing/epidemiología , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , Persona de Mediana Edad , Placa Aterosclerótica , Valor Predictivo de las Pruebas , Prevalencia , Estudios Retrospectivos , Medición de RiesgoRESUMEN
BACKGROUND: Coronary atherosclerosis and cognitive impairment are both age-related diseases, with similar risk factors. Coronary artery calcium (CAC), a marker of coronary atherosclerosis, may play a role in early detection of individuals prone to cognitive decline. This study aimed to investigate the relationship between CAC and cognitive function, and the capability of CAC to identify participants with a high risk of dementia in a Chinese community-based population. METHODS: A total of 1332 participants, aged 40-80 years and free of dementia from a community located in Beijing were included. All participants completed neurocognitive questionnaires and noncontrast CT examinations. Cognitive performance tests (including verbal memory, semantic fluency, executive function, and global cognitive function tests), the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CIDE) risk score, and the CAC score (CACS) were evaluated by questionnaires and CT. A CAIDE score ≥ 10 was considered to indicate a high risk of dementia in late-life. Participants were divided into three groups according to CACS (0, 1-399, ≥ 400). RESULTS: After adjusting for risk factors, CACS was significantly associated with verbal memory (r = -0.083, P = 0.003) and global cognitive function (r = -0.070, P = 0.012). The prevalence of a high risk of dementia in the subgroups of CACS = 0, 1-399, and ≥ 400 was 4.67%, 13.66%, and 24.79%, respectively (P < 0.001). Individuals with CACS ≥ 400 had a higher risk of CAIDE score ≥ 10 [OR = 2.30 (1.56, 4.56), P = 0.014] than those with CACS = 0. The receiver-operating characteristic curves showed that the capability of CACS to identify participants with a high risk of dementia was moderate (AUC = 0.70, 95% CI: 0.67-0.72,P < 0.001). CONCLUSIONS: CAC, a marker of subclinical atherosclerosis, was significantly associated with cognitive performance in verbal memory and global cognitive function. CAC had a moderate capability to identify participants with a high risk of dementia, independent of age, education, and other risk factors.
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BACKGROUND: Cardiovascular disease is the major cause of death worldwide. Hypoxia-mediated apoptosis in cardiomyocytes is a major cause of cardiovascular disorders. Treatment with vascular endothelial growth factor (VEGF) protein has been tested but operational difficulties have limited its use. However, with the advancements of gene therapy, interest has risen in VEGF-based gene therapy in cardiovascular disorders. However, the precise mechanism by which VEGF replenishment rescues post-hypoxia damage in cardiomyocytes is not known. OBJECTIVES: To investigate the effect of post-hypoxia VEGF121 expression using neonatal rat cardiomyocytes. METHODS: Cardiomyocytes isolated from neonatal rats were used to establish an in vitro model of hypoxia-induced cardiac injury. The effect of VEGF overexpression, alone or in combination with small-molecule inhibitors targeting calcium channel, calcium sensitive receptors (CaSR), and calpain on cell growth and proliferation on hypoxia-induced cardiomyocyte injury were determined using an MTT assay, TUNEL staining, Annexin V/PI staining, lactate dehydrogenase and caspase activity. For statistical analysis, a value of P<0.05 was considered to be significant. RESULTS: The effect of VEGF121 was found to be mediated by CaSR and calpain but was not dependent on calcium channels. CONCLUSIONS: Our findings, even though using an in vitro setting, lay the foundation for future validation and pre-clinical testing of VEGF-based gene therapy in cardiovascular diseases.
FUNDAMENTO: A doença cardiovascular é a principal causa de morte em todo o mundo. A apoptose mediada por hipóxia em cardiomiócitos é uma das principais causas de distúrbios cardiovasculares. O tratamento com a proteína do fator de crescimento endotelial vascular (VEGF, do inglês vascular endothelial growth factor) foi testado, mas as dificuldades operacionais limitaram seu uso. Entretanto, com os avanços da terapia gênica, aumentou o interesse na terapia gênica baseada no VEGF em doenças cardiovasculares. No entanto, o mecanismo preciso pelo qual a reposição de VEGF resgata os danos pós-hipóxia em cardiomiócitos não é conhecido. OBJETIVOS: Investigar o efeito da expressão de VEGF121 pós-hipóxia utilizando cardiomiócitos de ratos neonatos. MÉTODOS: Cardiomiócitos isolados de ratos neonatos foram utilizados para estabelecer um modelo in vitro de lesão cardíaca induzida por hipóxia. O efeito da superexpressão de VEGF, isolado ou em conjunto com inibidores de moléculas pequenas que têm como alvo os canais de cálcio, receptores sensíveis ao cálcio (CaSR, do inglês calcium-sensitive receptors) e calpaína, no crescimento e proliferação celular em lesão de cardiomiócitos induzidos por hipóxia, foram determinados com ensaio de MTT, coloração TUNEL, coloração com Anexina V/PI, lactato desidrogenase e atividade da caspase. Para análise estatística, um valor de p<0,05 foi considerado significativo. RESULTADOS: Verificou-se que o efeito do VEGF121 foi mediado por CaSR e calpaína, mas não foi dependente dos canais de cálcio. CONCLUSÕES: Nossos resultados, mesmo em um ambiente in vitro, estabelecem as bases para uma validação futura e testes pré-clínicos da terapia gênica baseada em VEGF em doenças cardiovasculares.
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Receptores Sensibles al Calcio , Factor A de Crecimiento Endotelial Vascular , Animales , Hipoxia , Mitocondrias , Miocitos Cardíacos/metabolismo , Péptido Hidrolasas/metabolismo , Ratas , Receptores Sensibles al Calcio/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Diabetes mellitus (DM) is considered a cardiovascular risk factor. The aim of this study was to analyze the prevalence and volume of coronary artery plaque in patients with diabetes mellitus (DM) vs. those without DM. METHODS: This study recruited consecutive patients who underwent coronary computed tomography (CT) angiography (CCTA) between October 2016 and November 2017. Personal information including conventional cardiovascular risk factors was collected. Plaque phenotypes were automatically calculated for volume of different component. The volume of different plaque was compared between DM patients and those without DM. RESULTS: Among 6381 patients, 931 (14.59%) were diagnosed with DM. The prevalence of plaque in DM subjects was higher compared with nondiabetic group significantly (48.34% vs. 33.01%, χâ=â81.84, Pâ<â0.001). DM was a significant risk factor for the prevalence of plaque in a multivariate model (odds ratio [OR]â=â1.465, 95% CI: 1.258-1.706, Pâ<â0.001). The volume of total plaque and any plaque subtypes in the DM subjects was greater than those in nondiabetic patients significantly (Pâ<â0.001). CONCLUSION: The coronary artery atherosclerotic plaques were significantly higher in diabetic patients than those in non-diabetic patients.
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Angiografía por Tomografía Computarizada/métodos , Vasos Coronarios/diagnóstico por imagen , Placa Aterosclerótica/diagnóstico por imagen , Anciano , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
OBJECTIVE: We sought to distinguish lipid plaques using a CT quantitative pixel density histogram, based on the pathological diagnosis of lipid cores as the gold standard. MATERIALS AND METHODS: Eight patients awaiting heart transplantation due to end-stage coronary heart disease underwent coronary CT angiography (CCTA) spectroscopy prior to heart transplantation; coronary artery pathological analysis was performed for all patients. Lipid-core plaques were defined pathologically as manifesting a lipid core diameter > 200 µm, a circumference > 60 degrees, and a cap thickness < 450 µm. The percentage distributions of CT pixel attenuation ≤ 20, 30, 40, and 50 HU were calculated using quantitative histogram analysis. RESULTS: A total of 271 transverse sections were co-registered between CCTA and pathological analysis. Overall, 26 lipid cores and 16 fibrous plaques were identified by pathological analysis. There was no significant difference in median CT attenuation between the lipid and fibrous plaques (51 HU [interquartile range, 46-63] vs. 57 HU [interquartile range, 50-64], p = 0.659). The median percentage of CT pixel attenuation ≤ 30 HU accounted for 11% (5-17) of lipid-core plaques and 0% (0-2) of fibrous plaques (p < 0.001). The sensitivity and specificity of the method for diagnosing lipid plaques by the average CT pixel attenuation ≤ 30 HU were 80.8% and 87.5%, respectively. The area under the receiver operator characteristics curve was 0.898 (95% confidence interval: 0.765-0.970; 3.0% was the best cut-off value). The diagnostic performance was significantly higher than those of the average pixel CT attenuation percentages ≤ 20, 40, and 50 HU and the mean CT attenuation (p < 0.05). CONCLUSION: In in vivo conditions, with the pathological lipid core as the gold standard, quantification of the percentage of average CT pixel attenuation ≤ 30 HU in the histogram can be useful for accurate identification of lipid plaques.
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Angiografía por Tomografía Computarizada/métodos , Enfermedad Coronaria/diagnóstico , Vasos Coronarios/patología , Lípidos/análisis , Adulto , Anciano , Área Bajo la Curva , Enfermedad Coronaria/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Femenino , Fibrosis , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROC , Sensibilidad y EspecificidadRESUMEN
RATIONALE AND OBJECTIVES: We sought to compare the prevalence and volume of lipid plaque, fibrous plaque, and calcified plaque in patients with smokers versus nonsmokers. MATERIALS AND METHODS: We studied consecutive patients suspected of coronary artery disease and who underwent coronary computed tomography angiography. A structured interview and review of existing clinical data was conducted before computed tomography angiography to collect information on demographic characteristics, the presence of cardiovascular risk factors. The volume of lipid, fibrous, and calcified plaque were automatically calculated and marked in different colors according to predefined Hounsfield unit thresholds. The prevalence and volume of plaques were compared between smokers and nonsmokers. RESULTS: Overall 6380 patients (3351 men and 3029 women, mean age 55.35 years) were finally analyzed, of whom 2075 (32.5%) were smokers, and 4305 (67.5%) were never smokers. The prevalence of any plaque in smokers was significantly higher compared to never smokers (47.7% vs. 32.3%, p < 0.001). Smoking was an independent risk factor of the presence of any plaque after correcting for age, gender, body mass index, hypertension, dyslipidemia, diabetes, and family history in a multivariate model (odds ratioâ¯=â¯1.250 (1.088-1.437), p = 0.002). The volume of lipid plaque, fibrous plaque, calcified plaque, and total plaque in smokers was significantly greater than nonsmokers (p < 0.001). CONCLUSION: The prevalence and volume of lipid plaque, fibrous plaque, and calcified plaque were significantly higher in smokers versus never smokers.
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Angiografía por Tomografía Computarizada/métodos , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico , No Fumadores , Placa Aterosclerótica/diagnóstico , Fumadores , Fumar/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Resumo Fundamento: A doença cardiovascular é a principal causa de morte em todo o mundo. A apoptose mediada por hipóxia em cardiomiócitos é uma das principais causas de distúrbios cardiovasculares. O tratamento com a proteína do fator de crescimento endotelial vascular (VEGF, do inglês vascular endothelial growth factor) foi testado, mas as dificuldades operacionais limitaram seu uso. Entretanto, com os avanços da terapia gênica, aumentou o interesse na terapia gênica baseada no VEGF em doenças cardiovasculares. No entanto, o mecanismo preciso pelo qual a reposição de VEGF resgata os danos pós-hipóxia em cardiomiócitos não é conhecido. Objetivos: Investigar o efeito da expressão de VEGF121 pós-hipóxia utilizando cardiomiócitos de ratos neonatos. Métodos: Cardiomiócitos isolados de ratos neonatos foram utilizados para estabelecer um modelo in vitro de lesão cardíaca induzida por hipóxia. O efeito da superexpressão de VEGF, isolado ou em conjunto com inibidores de moléculas pequenas que têm como alvo os canais de cálcio, receptores sensíveis ao cálcio (CaSR, do inglês calcium-sensitive receptors) e calpaína, no crescimento e proliferação celular em lesão de cardiomiócitos induzidos por hipóxia, foram determinados com ensaio de MTT, coloração TUNEL, coloração com Anexina V/PI, lactato desidrogenase e atividade da caspase. Para análise estatística, um valor de p<0,05 foi considerado significativo. Resultados: Verificou-se que o efeito do VEGF121 foi mediado por CaSR e calpaína, mas não foi dependente dos canais de cálcio. Conclusões: Nossos resultados, mesmo em um ambiente in vitro, estabelecem as bases para uma validação futura e testes pré-clínicos da terapia gênica baseada em VEGF em doenças cardiovasculares.
Abstract Background: Cardiovascular disease is the major cause of death worldwide. Hypoxia-mediated apoptosis in cardiomyocytes is a major cause of cardiovascular disorders. Treatment with vascular endothelial growth factor (VEGF) protein has been tested but operational difficulties have limited its use. However, with the advancements of gene therapy, interest has risen in VEGF-based gene therapy in cardiovascular disorders. However, the precise mechanism by which VEGF replenishment rescues post-hypoxia damage in cardiomyocytes is not known. Objectives: To investigate the effect of post-hypoxia VEGF121 expression using neonatal rat cardiomyocytes. Methods: Cardiomyocytes isolated from neonatal rats were used to establish an in vitro model of hypoxia-induced cardiac injury. The effect of VEGF overexpression, alone or in combination with small-molecule inhibitors targeting calcium channel, calcium sensitive receptors (CaSR), and calpain on cell growth and proliferation on hypoxia-induced cardiomyocyte injury were determined using an MTT assay, TUNEL staining, Annexin V/PI staining, lactate dehydrogenase and caspase activity. For statistical analysis, a value of P<0.05 was considered to be significant. Results: The effect of VEGF121 was found to be mediated by CaSR and calpain but was not dependent on calcium channels. Conclusions: Our findings, even though using an in vitro setting, lay the foundation for future validation and pre-clinical testing of VEGF-based gene therapy in cardiovascular diseases.